Frontal lobe

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  • Frontal Lobe ( lobus frontalis ). —On the lateral surface of the hemisphere this lobe extends from the frontal pole to the central sulcus, the latter separating it from the parietal lobe. Below, it is limited by the posterior ramus of the lateral fissure, which intervenes between it and the central lobe. On the medial surface, it is separated from the cingulate gyrus by the cingulate sulcus; and on the inferior surface, it is bounded behind by the stem of the lateral fissure.
  • The lateral surface of the frontal lobe (Fig. 726) is traversed by three sulci which divide it into four gyri: the sulci are named the precentral, and the superior and inferior frontal; the gyri are the anterior central, and the superior, middle, and inferior frontal. The precentral sulcus runs parallel to the central sulcus, and is usually divided into an upper and a lower part; between it and the central sulcus is the anterior central gyrus. From the precentral sulcus, the superior and inferior frontal sulci run forward and downward, and divide the remainder of the lateral surface of the lobe into three parallel gyri, named, respectively the superior, middle, and inferior frontal gyri. T he anterior central gyrus ( gyrus centralis anterior; ascending frontal convolution; precentral gyre ) is bounded in front by the precentral sulcus, behind by the central sulcus; it extends from the supero-medial border of the hemisphere to the posterior ramus of the lateral fissure. The superior frontal gyrus ( gyrus frontalis superior; superfrontal gyre ) is situated above the superior frontal sulcus and is continued on to the medial surface of the hemisphere. The portion on the lateral surface of the hemisphere is usually more or less completely subdivided into an upper and a lower part by an antero-posterior sulcus, the paramedial sulcus, which, however, is frequently interrupted by bridging gyri. The middle frontal gyrus ( gyrus frontalis medius; medifrontal gyre ), between the superior and inferior frontal sulci, is continuous with the anterior orbital gyrus on the inferior surface of the hemisphere; it is frequently subdivided into two by a horizontal sulcus, the medial frontal sulcus of Eberstaller, which ends anteriorly in a wide bifurcation. The inferior frontal gyrus ( gyrus frontalis inferior; subfrontal gyre ) lies below the inferior frontal sulcus, and extends forward from the lower part of the precentral sulcus; it is continuous with the lateral and posterior orbital gyri on the under surface of the lobe. It is subdivided by the anterior horizontal and ascending rami of the lateral fissure into three parts, viz., (1)
  •  The medial surface of the frontal lobe is occupied by the medial part of the superior frontal gyrus ( marginal gyrus ) (Fig. 727). It lies between the cingulate sulcus and the supero-medial margin of the hemisphere. The posterior part of this gyrus is sometimes marked off by a vertical sulcus, and is distinguished as the paracentral lobule, because it is continuous with the anterior and posterior central gyri.
  • 1 the orbital part, below the anterior horizontal ramus of the fissure; (2) the triangular part ( cap of Broca ), between the ascending and horizontal rami; and (3) the basilar part, behind the anterior ascending ramus. The left inferior frontal gyrus is, as a rule, more highly developed than the right, and is named the gyrus of Broca, from the fact that Broca described it as the center for articulate speech. The inferior or orbital surface of the frontal lobe is concave, and rests on the orbital plate of the frontal bone (Fig. 729). It is divided into four orbital gyri by a well-marked H-shaped orbital sulcus. These are named, from their position, the medial, anterior, lateral, and posterior orbital gyri. The medial orbital gyrus presents a well-marked antero-posterior sulcus, the olfactory sulcus, for the olfactory tract; the portion medial to this is named the straight gyrus, and is continuous with the superior frontal gyrus on the medial surface.     64  
  • Phineas Gage and frontal lobe damage This year is the 150th anniversary of one of the world's most important on-the-job accidents. The accident injured only one worker, but it made medical history-and it taught us volumes about how the brain controls emotions and behavior. On September 13, 1848, railroad worker Phineas Gage was tamping blasting powder into a hole, using a three-and-a-half foot iron rod, when the powder exploded. The rod shot through Gage's skull, entering his left cheek and exiting through the top of his head. Amazingly, Gage survived this massive injury. In fact, one observer reported that Gage was able to walk away from the accident, "talking with composure and equanimity of the hole in his head." The long-term effects of Gage's accident, however, were devastating. Previously a polite and sociable gentleman, Gage became an antisocial, foul-mouthed, irresponsible, bad-mannered lout and unrepentant liar. According to his friends, he was "no longer Gage." He drifted from job to job, finally dying penniless. While Gage's life was ruined, his unfortunate accident taught researchers about the critical role of the brain's frontal lobes-the area of Gage's brain injured by the iron bar that penetrated his skull-in controlling behavior, emotions, and judgment. La a ater studies proved that injuries to the frontal lobes, or diseases that damage this brain area, can cause disinhibited behavior, poor judgment, and even antisocial or criminal behavior. Antonio Damasio and colleagues, who have studied a dozen patients with frontal lobe damage similar to Gage's, say that the patients are incapable of planning for the future, and are deficient in judgment, reasoning ability, and "moral insight." Other re e esearch links frontal lobe dysfunction to aggression, alcoholism, and psychopathic criminality, and suggests that the deviant behavior seen in many children with Fetal Alcohol Syndrome may stem from damage to this brain area. Problem #1 Phineas Gage is a hard-working, diligent, reliable, responsible, Intelligent. good-humored, deeply religious, family-oriented man until he is involved in an accident at which time an explosion occurs and a crowbar is driven into his brain. It transacts the orbit and pierces the frontal lobes. Amazingly, he has only a brief loss of consciousness and although he is rendered blind due to optic nerve damage, he has no other motor, sensory, language, or memory impairment. Over the course of time, several subtle and unfortunate changes in personality and behavior are noted. These include: 1. He becomes unreliable and fails to come to work and when present he is "lazy." 2. He has no interest in going to church, constantly drinks alcohol, gambles, and "whores about." 3. He is accused of sexually molesting young children. 4. He ignores his wife and children and falfls to meet his financial and family obligations. 5. He becomes "lazy" and fails to complete any task at work or at home. He has lost his sense of humor. 6. He curses constantly and does so in inappropriate circumstances. Questions 1. What portion of the brain ig most likely affected? 2. What is the function of this region? 3. Why are there no other cortical disturbances detected? Answers This case represents a classic example of frontal lobe injury. Located on the medial and undersurfaceof the frontal lobes is the limbic system. Dysfunction to the frontal lobe may result in profound behavioral abnormalities. In patients with "functional" psychiatric disorders (depression, anxiety, schizophrenia), metabolic abnormalities have been detected in the frontal lobes-"lobectomy" was performed in patients with severe mental illness. (A relic of one of the early neurosurgical instruments is on display in the pharmacy museum in the french quarter. Modern neurosurgery is more advanced. Somewhat.) 2. In addition to the personality and behavioral features, the frontal lobes play a role in these mental tasks: sustaining attention shifting attention initiating mental and motor activity inhibiting socially unaccepatable behavior (words or actions) 3. Because the injury spared the language, memory, motor, sensory, and visual cortex regions, there are no other neurological impairments. It is truly amazing the Phineas Gage survived his injury and that there were no other neurological impairments except that "Phineas Gage was no longer Phineas Gage."
  • Frontal Lobe Syndrome Frontal lobe syndrome is a disorder affecting the prefrontal areas of the frontal lobe. The prefrontal lobe comprises the vast area of the frontal lobe anterior to the motor cortex and includes the undersurface of the frontal lobe, or the orbital region. The frontal lobe syndrome is said to be present when an individual who is previously capable of judgment and sustained application and organization of his life becomes aimless and improvident, and may lose tact, sensitivity, and self-control. Additionally, the individual affected by pathology in the prefrontal cortex may demonstrate impulsiveness and a failure to appreciate the consequences of his or her reckless behavior.1 Frontal lobe syndrome can be caused by head trauma or may be the consequence of brain tumor, cerebrovascular accident, infection, or a degenerative cortical disease such as Pick's disease.2 This syndrome represents an organic explanation for psychologically-based symptoms the patient may demonstrate. Due to the anterior location of the prefrontal region, lesions to this region may be missed on a standard neurological examination or on a cursory mental status examination. The mental changes produced by lesions in the prefrontal region have led to the recognition of the "frontal lobe personality," as the patient tends to demonstrate specific personality changes which are more often revealed by a qualitative analysis of the patient's attitudes and types of errors produced rather than by a crude quantitative analysis of performance.3 The behavioral changes associated with bilateral prefrontal lesions may be difficult to measure, but family, friends, and employers may tell you that the patient is "no longer the same."4 Following a head injury, personality change in the injured patient is frequently reported and is often cited by family members as the most difficult and persistant problem that they face. Spouses of patients with frontal lobe syndrome relate that "it is like living with a different person," or that the patient "is not the person I married." Post-traumatic personality changes seen with injuries to the prefrontal region may result in marital break-up, social isolation, or unemployment, as some are fired from their jobs because of inadequate performance or because of offending their co-workers.1,2,4,5,6 Compounding the problem in the identification of prefrontal involvement is the dissociation between how well a patient with a bifrontal lesion can appear during the initial office visit and how poorly they actually perform in real life.4 The consequences of damage to the prefrontal region include: alterations of attention concrete thinking perseveration reduced activity disturbed affect The frontal lobe syndrome patient may demonstrate an attention deficit. The patient may appear slow, uninterested, may lack spontaneity, may be easily distracted by irrelevant environmental stimuli, and may be unable to sustain attention. The patient's disinterest and easy distractibility may contribute to an apparent poor memory. The frontal lobe syndrome patient's memory is normal, but absentmindedness may lead to the appearance of a memory deficit as the patient literally "forgets to remember" and has the inability to focus attention long enough to form the rudiments of memory. These patients may fill in memory gaps with confabulation, or the elaboration of imaginary facts and experiences to fill in their gaps of knowledge or memory.2,3,4,5,6 These patients may also engage in concrete thinking, which is an impairment of abstract thought. This trend may be identified during a basic mental status evaluation by the patient's inability to properly interpret proverbs.2,4 Closely linked to concrete thinking is the demonstration of "utilization behavior" in which the patient has the tendency to manually grasp and use objects presented within reach.2,3 Perseveration is common in frontal lobe syndrome patients and is the tendency to maintain a previously established motor pattern without modifying the activity according to the demands of the changing environment because of an inability to shift from one line of thinking to another.2,3,4 When faced with a series of different motor tasks, the patient may end up performing one component of the series of tasks over and over again and may demonstrate great difficulty, or an inability to change motor patterns. Perseveration is one of the reasons for poor job performance in the frontal lobe syndrome patient. These patients may demonstrate a diminution of spontaneous activity, a lack of drive, an inability to plan ahead, a lack of concern, and possible bouts of restlessness and aimless, uncoordinated behavior.1-6 These findings may also contribute to poor job performance and family relations. Lastly, the frontal lobe syndrome patient may demonstrate a disturbance of affect ranging from complete apathy to disinhibition depending upon the location of the lesion. A lesion to the dorsolateral aspect of the prefrontal region may produce apathy, emotional blunting, and an indifference to the surrounding world. Their apathy may be noted during examination and may extend toward work and family. These patients may become incontinent, not because of a lesion affecting bladder function, but because of a disregard for their surroundings and the consequences of their actions. Conversely, a patient with a lesion to the orbital region of the prefrontal lobe, or the underside, may exhibit disinhibition, a failure to appreciate the consequences of one's actions, and euphoria with a tendency to jocularity. These patients may exhibit moria (childish excitement), joking and pathological punning, sexual indiscretions, and exhibitionism.1-6 Thus, in the presence of an unremarkable neurological examination, these specific findings may be the only indication of an injury or an underlying pathology in the affected patient. Next month's column will stress simple testing procedures for frontal lobe syndrome. References Walton J. Brain Diseases of the Nervous System, 10th Edition, Oxford Medical Publishers, New York, 1993. Trimble MR. Behavior and personality disturbances, In: Bradley WG, Daroff RB, Fenichel GM, and Marsden CD, Neurology in Clinical Practice, Vol. I, Butterworth-Heinemann, Boston, 1991. Gainotti G. Frontal lobe damage and disorders of affect and personality, In: Swash M and Oxbury J, Clinical Neurology, Churchill-Livingstone, New York, 1991. Devinsky O. Behavioral Neurology, Mosby, St. Louis, 1992. Greenwood R, Barnes MP, McMillan TM, and Ward CD. Neurological Rehabilitation, Churchill-Livingstone, New York 1993. Strub RL and Black FW. The Mental Status Examination in Neurology, 3rd Ed. F.A. Davis, Philadelphia, 1991. The Frontal Lobe is the most anterior, right under the forehead. Functions: How we know what we are doing within our environment ( Consciousness ). How we initiate activity in response to our environment. Judgments we make about what occurs in our daily activities. Controls our emotional response. Controls our expressive language. Assigns meaning to the words we choose. Involves word associations. Memory for habits and motor activities. Observed Problems: Loss of simple movement of various body parts ( Paralysis ). Inability to plan a sequence of complex movements needed to complete multi-stepped tasks, such as making coffee ( Sequencing ). Loss of spontaneity in interacting with others. Loss of flexibility in thinking. Persistence of a single thought ( Perseveration ). Inability to focus on task ( Attending ). Mood changes ( Emotionally Labile ). Changes in social behavior. Changes in personality. Difficulty with problem solving. Inablility to express language ( Broca's Aphasia ). The frontal lobes are responsible for voluntary motor activity, speaking ability and elaboration   of thought.  The primary motor cortex, which is located in between the left hemisphere and somato sensory cortex, confers voluntary control over the movement produced by the skeletal muscles.  As in sensory processing, the motor cortex on each side of the brain primarily controls muscles on the opposite side of the body.  Damage to the motor cortex on the left side of the brain produces paralysis on the right side of the body and vice versa.  The frontal lobe extends from the central sulcus to the anterior limit of the brain.  The posterior portion of the frontal lobe is precentral gyrus, which is specialized for the control of fine movements, such as the movement of fingers one at a time.  The prefrontal cortex, the most anterior portion of the frontal lobe, is the only cortical area known to receive input from all sensory modalities.  This region was also the target of prefrontal lobotomies, a type of  brain surgery conducted in attempts to control certain types of psychological disorders.  As a result  of the surgery, patients showed impairments in certain aspects of memory and in their facial expressions of emotion. The frontal lobe can be divided into three functional zones: Motor cortex: Responsible for initiating voluntary movements Premotor cortex: Selects movements based on external cues. Prefrontal cortex: Ensures that the right movements are made at the time and place.
  • Supplementary Motor Area The supplementary motor area (SMA) occupies an expanse of frontal agranular cortex rostral to the primary motor cortex (MI), largely in the medial surface of the hemisphere. It is basically organized topographically, although the topography is not as apparent as in the MI. The traditionally defined SMA is now regarded as including two separate areas. The caudal part (SMA proper or F3) projects directly to the MI and to the spinal cord. The rostral part (pre-SMA or F6) is more remote from MI and receive projections from the prefrontal cortex and the cingulate motor areas. The supplementary eye field (SEF) is a small area separate from either the SMA or pre-SMA. The SEF is connected to cortical and subcortical areas related to oculomotor control. The SMA is active when subjects perform distal as well as proximal limb movement. The SMA activity is subject to functional plasticity. The SMA is more active than the primary motor cortex if motor tasks are demanding in certain respects. Similarities of lesion effects of the SMA and basal ganglia suggests their intimate relation linked anatomically by the cortico-basal ganglia loops. Studies in both human subjects and in subhuman primates indicate the importance of the SMA in motor tasks that demand retrieval of motor memory. The SMA appears also crucial in temporal organization of movements, especially in sequential performance of multiple movements. Transcortical motor aphasia - The lesion is anterior to Broca's area or in the supplementary motor area. The language syndrome is similar to Broca's except for preserved repetition and occasionally preserved writing. Language is a motoric component, therefore, we should become a bit more adpet at noticing subtle changes in cadence, prosadic variation, mistakes. Etc. Broca's Aphasia (= nonfluent = expressive = motor = anterior aphasia) - Broca's aphasia is seen in its pure form in lesions involving the inferior frontal gyrus. Due to the proximity of the precentral gyrus, there is typically an associated right central facial paresis and right hemiparesis (arm>leg). Speech is slow, effortful, and has articulatory errors. Phrase length varies from complete mutism to decreased number of words per sentence (2-3 with normal being 5-9). There is a parallel deficit in writing. Repetition, particularly short phrases ("no ifs, ands or buts")is severely disrupted. Comprehension is largely intact although detailed linguistic analysis reveals difficulty with prepositions such as into, on, etc. There is often associated anomia, production of paraphasic errors ("grish" for "dish") and oral facial apraxia. The apraxia is manifested by difficulty in sequencing oral movements. Patients may be able to hum a tune or sing words.
  • CONFABULATION (DELUSIONAL & FALSE MEMORIES) When secondary to right (or bilateral) frontal damage, speech may become exceedingly bizarre, delusional, and fantastical, as loosely associated ideas become organized and anchored around fragments of current experience. For example, one patient, when asked as to why he had been hospitalized, denied that there was anything wrong, but instead claimed he was there to do some work. When asked what kind of work, he pointed to the air conditioning unit, and stated: "I'm a repair man. I'm here to fix the air conditioner. Now, if you'd please excuse me. I've got work to do." A 24 year old store cleark who received a gunshot wound (during the course of a robbery) which resulted in destruction of the right inferior convexity and orbital areas, attributed his hospitalization to a plot by the government to steal his inventions (Joseph 1986a). He claimed he was a famous inventor, had earned millions of dollars and had even been on TV. When it was pointed out that he had undergone surgery for removal of bone fragments and the bullet, he pointed to his head and replied, "that's how they are stealing my ideas." Another patient, formerly a janitor, who suffered a large right frontal subdural hematoma (which required evacuation) soon began claiming to be the owner of the business where he formerly worked (Joseph 1988a). He also alternatively claimed to be a congressman and fabulously wealthy. When asked about his work as a janitor he reported that as a congressman he had been working under cover for the C.I.A. Interestingly, this patient, also stated he realized what he was saying was probably not true. "And yet I feel it and believe it though I know it's not right." Frontal lobe confabulation seems to be due to disinhibition, difficulties monitoring responses, withholding answers, utilizing external or internal cues to make corrections, accessing appropriate memories, maintaining a coherent line of reasoning, or suppressing the flow of tangential and circumstantial ideas (Fischer et al. 1995; Joseph 1986a,1988a, 1999a; Johnson, O'Connor and Cantor 1997; Kapur and Coughlan 1980; Shapiro et al.1981; Stuss et al. 1978; Stuss and Benson 1986). That is, since the right frontal lobe can no longer regulate information processing and the flow of perceptual and ideational activity, information that is normally filtered out and suppressed is instead expressed. In consequence, the Language Axis of the left hemisphere becomes overwhelmed and flooded by irrelevant, bizarre associations, leading sometimes to the expression of false memories, which the patient (that is, Broca's area) repeats (Joseph, 1982, 1986ab, 1988ab). As noted, in some respects injuries involving the orbital frontal lobes can result in symptoms similar to those with right frontal injuries, including the production of confabulatory ideation. However, in contrast to right (or bilateral) frontal injuries which may result in the production of fantastical spontaneous confabulations where contradictory facts are ignored or simply incorporated, confabulatory responses associated with orbital injuries tend to be more restricted, transitory, and in some cases must be provoked (Fischer et al. 1995).
  • THE RIGHT FRONTAL LOBE AND THE REGULATION OF AROUSAL The right cerebral hemisphere is clearly dominant in regard to the mediation and control over most aspects of social-emotional functioning (chapter 10). There is also a variety of findings which strongly suggest that the so called alerting/arousal vigilance network is localized to the right frontal lobe (Posner & Raichle, 1994), and that the right frontal lobe exerts bilateral influences on arousal (DeRenzi & Faglioni, 1965; Heilman & Van Den Abell, 1979, 1980; Joseph, 1982, 1986a, 1988a, 1999a; Konishi, et al., 1999; Tucker, 1981). For example, the intact, normal right hemisphere is quicker to react to external stimuli, and has a greater attentional capacity compared to the left (Dimond, 1976, 1979; Heilman & Van Den Abell, 1979; Jeeves & Dixon, 1970; Joseph, 1988ab). In split brain studies the isolated left hemisphere tends to become occasionally unresponsive, suffers lapses of attention, and is more limited in attentional capacity as compared to the right which attends to both the left and right half of visual, auditory, and tactile space (Dimond 1976, 1979; Joseph 1986a, 1988ab). Indeed, visual and somesthetic stimuli, or active touch exploration with either the right or left hand, elicits evoked EEG responses preferentially and of greater magnitude over the right hemisphere and right frontal lobe (Desmedt 1977). The right hemisphere also becomes desynchronized (aroused) following left or right sided stimulation (indicating it is bilaterally responsive), whereas the left brain is activated only with unilateral (right side) stimulation (Heilman & Van Dell Abell, 1980). In fact, the right frontal lobe and hemisphere responds more quickly even to stimuli appearing on the right side (Dimond 1976 1979; Heilman and Van Den Abell 1979, 1980; Jeeves and Dixon 1970). In consequence, if the right frontal lobe (or hemisphere) is injured, the left frontal lobe is unable to attend to events occurring on the left side of the body, which results in unilateral left-side neglect. The right frontal lobe is also larger than the left suggesting a greater degree of interconnections with other brain tissue, and it appears to exert bilateral inhibitory influences on attention and arousal (Cabeza and Nyberg 1997; DeRenzi and Faglioni 1965; Dimond 1976 1979; Heilman and Van Den Abell 1979, 1980; Jeeves and Dixon 1970; Joseph 1986a, 1988ab; Konishi et al., 1999; Pardo et al. 1991; Tucker 1981). For example, as based on functional imaging, it has been found that when performing a "go/no-go task" and the Wisconsin Card Sort--tasks requiring the inhibition of irrelevant or erroneous responses, activity significantly increases in the right inferior frontal lobe, and that this was the case irrespective of if the human subjects used the right or left hand (Konishi et al., 1999). By contrast, the left frontal region appears to exert unilateral excitatory influences which promotes right sided motor control and speech expression. However, because the right frontal lobe appears to exert bilateral inhibitory influences, whereas the influences of the left are unilateral and excitatory, when the left frontal region is damaged, the right may act unopposed and there may be excessive left cerebral inhibition or reduced activity (e.g., Bench et al., 1995); for example, as manifested by speech arrest, depression, and/or apathy. Nevertheless, because left cerebral excitatory influences are predominantly unilateral, with massive right cerebral damage, although the left hemisphere is aroused, the left is unable to activate the right half of the brain. This may result in unilateral inattention and neglect of the left half of the body and space (Heilman & Valenstein, 1972; Joseph, 1986a, 1988a; Na et al., 1999). That is, the patient's (undamaged) left hemisphere may ignore his of her left arm or leg, and if their neglected extremities are shown to them, may claim they belong to the doctor or a person in the next room. That such disturbances occur only rarely with left frontal or left hemisphere damage further suggests that the right hemisphere is able to continue to monitor events ocurring on either side of the body. Thus although the damaged left hemishere is hypoaroused (or inhibited by the right), there is little or no neglect. However, with lesions involving the right frontal lobe, not only is there a loss of inhibitory control, but the left may act unopposed such that there is excessive excitement. The patient becomes disinhibited as manifested by speech release, confabulation, lability, and a host of impulsive disturbances which may wax and wane in severity. As detailed below, mania, confabulation, hypersexuality, tagentiality, and impulsive, labile, disinhibited and inappropriate social and emotional behaviors are predominately associated with right frontal dysfunction (Bogousslavsky et al. 1988; Clark and Davison 1987; Cohen and Niska 1980; Cummings and Mendez 1984; Fischer et al. 1995; Forrest 1982; Girgis 1971; Jack et al. 1983; Jamieson and Wells 1979; Joseph 1986a, 1988a, 1999a; Kapur and Coughlan 1980; Lishman 1973; Miller et al. 1986; Oppler 1950; Rosenbaum and Berry 1975; Shapiro et al.1981; Starkstein et al. 1987; Stern and Dancy 1942; Stuss and Benson 1986); a function of loss of inhibitory control as well as its role in all aspects of emotion. In fact, and as originally pointed out by Lisman (1968, 1973), injuries to the right frontal lobe are clearly associated with what has been described as the "frontal lobe personality," including, in the extreme, the development of a full blown manic psychosis coupled with disinhibited sexuality.
  • THE FRONTAL LOBE PERSONALITY by Rhawn Joseph, Ph.D. The frontal lobes serve as the "Senior Executive" of the brain and personality, acting to process, integrate, inhibit, assimilate, and remember perceptions and impulses received from the limbic system, striatum, temporal lobes, and neocortical sensory receiving areas (Fuster 1997; Joseph 1986a; Koechlin et al., 1999; Milner and Petrides 1984; Passingham 1993; Selemon et al. 1995; Shallice and Burgess 1991; Stuss 1992; Stuss and Benson 1986; Strub and Black 1993; Van Hosen et al., 1996). Through the assimilation and fusion of perceptual, volitional, cognitive, and emotional processes, the frontal lobes engages in decision making and goal formation, modulates and shapes character and personality and directs attention, maintains concentration, and participates in information storage and memory retrieval (Dolan et al., 1997; Joseph, 1986a, 1988a, 1999a; Kapur et al., 1995; Passingham, 1997; Posner & Raichle, 1994; Tulving et al., 1994). The frontal neocortex is "interlocked" with the limbic system, striatum, and the primary and secondary receiving areas via converging and reciprocal connections, and receives verbal and ideational impulses transmitted from the multi-modality associational areas including Wernicke's area and the inferior parietal lobule (Cavada 1984; Fuster 1997; Jones and Powell 1970; Goldman-Rakic 1995, 1996; Passingham, 1993, 1997; Pandya & Yeterian 1990; Petrides & Pandya 1988). It is thus able to act at all levels of information analysis. THE FRONTAL LOBE PERSONALITY With unilateral, bilateral, or even seemingly mild frontal lobe dysfunction patients may initially display an array of waxing and waning abnormalities including the "frontal lobe personality," i.e. tangentiality, childishness, impulsiveness, jocularity, grandiosity, irritability, increased sexuality, and manic excitement (Joseph, 1988a, 1999a; Lishman, 1973). Over fifty years of research and numerous case studies have consistently indicated that with significant frontal lobe pathology attentional functioning may become grossly comprised, behavior may become fragmented, and initiative, goal seeking, concern for consequences, planning skills, fantasy and imagination, and the general attitude toward the future may be lost. The patient's range of interests may shrink, they may be unable to adapt to new situations or carry out complex, purposive, and goal directed activities, and lack insight, judgement, and common sense (Fuster 1997; Freeman and Watts 1942; Girgis 1971; Hacaen 1964; Joseph 1986a, 1988a, 1999a; Luria 1980; Passingham 1993; Petrie 1952; Stuss 1991; Stuss and Benson 1986). Conversely, when engaging in memory, planning, decision making, goal formation, and tasks requiring imagination, the frontal lobes become highly active--as demonstrated by functional imaging (Brewer et al., 1998; Passingham, 1997; Wagner et al., 1998; Dolan et al., 1997; Squire, et al,. 1992; Tulving et al., 1994; Kapur et al., 1995). With massive trauma, stroke, neoplasm or surgical destruction (i.e. frontal lobotomy), patients may show a reduction in activity and take very long to achieve very little. They may be unconcerned about their appearance, their disabilities, and demonstrate little or no interest in self-care or the manner in which they dress, or even if their clothes are soiled or inappropriate (Bradford 1950; Broffman 1950; Freeman and Watts 1942; Petrie 1952; Strom-Olsen 1946; Stuss 1991; Stuss and Benson 1986; Tow 1955). Although some patients demonstrate restlessness, impulsiveness, and flight of ideas, they may also tire easily, show careless work habits and a desire to get things over with quickly. As repeatedly documented following frontal lobotomy, they may immediately develop a tendency to lie in bed unless forcibly removed (Broffman 1950; Freeman and Watts 1942 1943; Rylander 1948; Tow 1955). Even with mild and subtle frontal lobe damage, patients may seem to take hours to get dressed, to finish their business in the bathroom, or to shop and purchase simple items. For example, patients may spend hours in the bathtub playing with the bubbles. A curious mixture of obsessive compulsiveness and passive aggressiveness may be suggested by their behavior. In severe cases, compulsive utilization of utensils and tools may occur, as well as distractability and perserveration. For example, following frontal lobotomy, "sometimes a pencil and a piece of paper will be enough to start an endless letter that may end up with the mechanical repitition of a certain phrase, line after line and even page after page" (Freeman and Watts 1943, p. 801). Even with "mild" to moderate frontal lobe injuries patients may initially demonstrate periods of tangentiality, grandiosity, irresponsibility, laziness, hyperexcitability, promiscuity, silliness, childishness, lability, personal untidiness and dirtiness, poor judgment, irritability, fatuous jocularity, and tendencies to spend funds extravagantly. Unconcern about consequences, tactlessness, and changes in sex drive and even hunger and appetite (usually accompanied by weight gain) may occur, coupled with a reduction in the ability to produce original or imaginative thinking. DISINHIBITION AND IMPULSIVENESS Following lobotomy or massive or even mild frontal injuries patients may become emotionally labile, irritable, euphoric, aggressive, and quick to anger, and yet be unable to maintain a grudge or a stable mood state as they rapidly oscillate between emotions (Bradford 1950; Greenblatt 1950; Joseph 1986a, 1999a; Rylander 1939; Strom-Olsen 1946; Stuss 1991; Stuss and Benson 1986). Depending on the degree of damage, they may become unrestrained, overtalkative, and tactless, saying whatever "pops into their head", with little or no concern as to the effect their behavior has on others or what personal consequences may result (Broffman 1950; Bogousslavasky et al. 1988; Freeman and Watts 1943; Joseph 1986a, 1999a; Luria 1980; Miller et al. 1986; Partridge 1950; Rylander 1939, 1948; Strom-Olsen 1946). With severe injuries patients may seem inordinantly disinhibited and influenced by the immediacy of a situation, buying things they cannot afford, lending money when they themselves are in need, and acting and speaking "without thinking." Seeing someone who is obese they may call out in a friendly manner, "Hey, fatty", and comment on their presumed eating habits. If they enter a room and detect a faint odor, its: "Hey, who farted?" Following severe injuries there may be periods of gross disinhibition which may consist of loud, boisterous, and grandiose speech, singing, yelling, and beating on trays. The destruction of furniture and the tearing of clothes is not uncommon. Some patients may impulsively strike doctors, nurses, or relatives and thus behave in a thoroughly labile, aggressive, callous and irresponsible manner (Benson and Geschwind 1971; Freeman and Watts 1942, 1943; Joseph 1986a, 1999a; Strom-Olsen 1946; Stuss and Benson 1986). One patient, with a tumor involving the right frontal area, following resection, attempted to throw a fellow patient's radio through the window because he did not like the music. He also loudly sang opera in the halls. Indeed, during the course of his examination he would frequently sing his answers to various questions (Joseph 1986a). Impulsiveness can also be quite subtle. Luria (1980, p. 294), describes one patient with a slowly growing frontal tumor "whose first manifestation of illness occurred when, on going to the train station, he got into the train which happened to arrive first, although it was going in the opposite direction." UNCONTROLLED LAUGHTER AND MIRTH Frontal lobe patients can act in a very childish and puerile manner, laughing at the most trivial of things, making inappropriate jokes, teasing, and engaging total strangers in hillarious conversation (Ackerley 1935; Freeman and Watts 1942, 1943; Kramer 1954; Luria 1980; Petrie 1952; Rylander 1939, 1948; Stuss and Benson 1986). Pathological laughter, joking, and punning may occur superimposed upon a labile effect. Many are vastly amused by their own jokes (Ironside 1956; Kramer 1954; Martin 1950). They can be quite funny, but often they are not! In part, frontal lobe humor is a function of tangentiality and disinhibition. Loosely connected ideas are strung together in an unusual fashion. The tendency to exaggerate and to impulsively comment upon whatever draws their attention is also contributory, and their humor and laughter may have a contagious quality. Nevertheless, rather than funny, frontal patients may seem crude and inappropriate. They may laugh without reason and with no accompanying feelings of mirth. These disturbances were in fact documented over 50 years ago. Kramer (1954) for example, describes 4 cases of uncontrollable laughter after lobotomy. They were unable to stop their laughter on command or upon their own volition. The laughter would come on like spells, occurring up to a dozen times a day, and/or continue into the night, requiring sedation in some cases. In these instances, however, the laughter had no contagious aspects but seemed shrill and "frozen." When questioned about the laughter the patients either confabulated a reason for their mirth, or seemed completely perplexed as to the cause. THE ORBITAL FRONTAL PERSONALITY Focal tumors of the orbital regions have also been reported to give rise to gelastic seizures (Chen and Foster 1973; Daly and Moulder 1957; Loiseau, Cohandon, and Cohandon 1971); that is, seizures which induce uncontrolled laughter. In fact, with lesions localized to the orbital frontal lobes patients may become disinhibited, hyperactive, euphoric, extroverted, labile, overtalkative, and develop perseveratory tendencies (Butter 1969; Butter et al. 1970; Greenblatt 1950; Joseph 1999a; Kennard et al. 1941; Kolb et al. 1974; Malloy, Birhlr, and Duffy 1993; Reitman 1946 1947; Ruch and Shenkin 1943). Proneness to criminal behavior, promiscuity, gradiosity, and paranoia have also been observed (Blumer and Benson 1975; Lishman 1973; Luria 1980; Raine et al. 1994; Stuss and Benson 1986). In general, right orbital damage seems to result in the most severe alterations in mood and emotional functioning (Grafman et al. 1986), which in turn is likely a function of the greater role of the right frontal lobe and the right hemisphere including the right inferior frontal lobe, in the regulation of emotion and arousal (Joseph, 1986a, 1988a, 1999a; Konishi et al., 1999; Tucker, 1981). In addition to laughter, punning and "Witzelsucht" (puerility), language might become excessively and inappropriately profane, and the patient may seem inordinately inconsiderate, outspoken, and obstinant (Broffman 1950; Partridge 1950; Strom-Olsen 1944; Stuss 1991; Stuss and Benson 1986). However, although they may easily swear, laugh, joke, and make threats, they may also become inordinately apathetic and listless, spending much of their time doing nothing. Alteration of Behavior and Personality A lack of initiative and spontaneity is the most common effect of frontal lobe disease and much easier to observe than to quantitative. With relatively mild form of this disorder, patient exhibit and idleness of thought, speech and action and they lapse into this state without complaints. They are tolerant to most condition in which they are placed, though they may may act unreasonably for brief period if irritated, seemingly being unable to think through the consequence of their remonstrance. They let member of the family answer questions and do the talking interjecting a remark only rarely. Question directed to such patients may evoke only a brief, unqualified answer.. Once started on a task they may persist in it (“stimulus bound”) I.e. thy tend to perseverate. Fluster emphasize the failure over time to maintain events in serial order and to integrate new events and information with previously learned data. Placidity: worry, anxiety, self concern, hypochondriasis, and pain reduces Psychomotor retardation: number of movements, spoken words and thought per unit of time diminish. Mild form abulia and severe akinetic mutism. Poorly localized to bilateral ventromedial frontal and fronto-diencephalic connections. INTELLECTUAL DEFICITS AND LACK OF CONCERN FOR LONG TERM CONSEQUENCES It has frequently been claimed that intelligence is not effected even with massive injuries to the frontal lobes. However, this view is completely erroneous for even in mild cases, although intelligence per se may not seem to be reduced as based on IQ testing, the ability to effectively employ one's intelligence is almost always compromised. Frontal lobe damage and lobotomy reduces one's ability to profit from experience, to anticipate consequences, or to learn from errors (Bianchi 1922; Drewe 1974; Goldstein1944; Halstead 1947; Milner 1964 1971; Nichols and Hunt 1940; Joseph 1986a, 1999a; Petrie 1952, Porteus and Peters 1947; Rylander 1939; Shallice and Burgess 1991; Stuss and Benson 1986; Tow 1955). There is a reduction in creativity, fantasy, dreaming, and abstract reasoning. The capacity to synthesize ideas into concepts or to grasp situations in their entirety is lost, and interests of an intellectual nature are diminished, or sometimes abolished. As described by Freeman and Watts (1943, p. 803) "patients who were great readers of good literature will be interested only in comic books or movie magazines. Men of considerable intellectual achievement... when discussion turns on the great events of the day will pass off some cliches as their own opinions". In mild or severe cases thinking may be contaminated by perseverative intrusions of irrelevant and tangential ideas, randomly formed associations, and illogical intellectual activity. These patient are also often effected by the immediacy of their environment and have difficulty making plans or adequately meeting long term goals. Even if highly intelligent, they may no longer be able to use that intelligence affectively, and they may undergo a complete personality change. In 1981, following his graduation from Stanford University, D.F., and three friends, founded their own electronics/computer company, which immediately became a modest success, and began to rapidly grow and expand. D.F., tall, lanky, clumsy, already losing his hair, and only 27 years old, was an electronics genius and in all respects the classic "nerd." He had never dated, and never had a social life, and throughout his younger years had been treated like a "retard" by his school mates. Although he was "vice president" of his company, and a co-owner, and worth over seven figures, he simply lacked the self-confidence to mingle or socialize with the opposite sex, and didn't feel comfortable interacting with anyone who did not share his enthusiasm for computers. Neverthless, D.F. was lonely. He needed a girlfriend. In 1985 his company "went public" (made a public offering of stock) and D.F. was suddenly a multi-millionaire without a girlfriend. It was soon thereafter that a "new girl" was hired to work as an assistant and secretary, just outside his office. "She was beautiful! An angel! Long blond hair. Green eyes. She must have weighed only 100 pounds. Everytime I walked out side my office I felt shocked to see her. And she wasn't married. She was only 23. I started thinking about her all the time. I coudn't concentrate. I dreamed about her. I wanted to marry her. I loved her. Love her!" he gushed, his words racing. But D.F. didn't have the nerve to approach her, or talk to her, except to say hi. "She always smiled at me, when I said hi. A big smile. I knew she liked me." But he still didn't ask her out. Instead, he began to fantasize, about being married, having children. And then after several tortured months, D.F. came to a decision. "I bought her a huge diamond ring. Ten thousand dollars. And I asked her to marry me." According to D.F., he simply approacher her, offered her the ring, which she took and put on her finger. And then he asked her to marry him. Apparently she was stunned. Apparently she even laughed. Apparently she even thanked him for the ring. But she said no. D.F. was mortified and became massively depressed. He couldn't function. Couldn't think."I just wanted to die." D.F. purchased a handgun. Took it home. Placed the barrel in his mouth. But then aimed it incorrectly. He pointed it directly into the roof of his mouth, pulled the trigger, and then blew out his right frontal lobe. Approximately six months later, D.F. arrived for his appointment to see me, with a toothbrush, toothpaste, hair brush, and wash rag sticking out of his shirt pocket (Joseph 1988a). When I asked, pointing at his pocket, "What's all that for?" he replied with a laugh, "That's just in case I want to brush my teeth," and in so saying he quickly drew the toothbrush from his pocket and began to demonstrate. During the course of the exam he laughingly demonstrated how the skin flap which covered the hole in his head (from the craniotomy and bullet wound) could bulge in or out when he held his breath or held his head upside down. He even climbed up and stood on this examiner's desk and bent over so as to offer a better view of the hole in his head. Throughout the exam he behaved in a silly, pueril manner, often joking and laughing inappropriately. Even when discussing the blond secretary and the aftermath, he laughed, becoming serious for only a few moment when I asked him if she had given him back the ring. She hadn't. Nevertheless, despite his bizarre and inappropriate behavior, D.F.'s overall WAIS-R IQ was above 130 (98% rank: "Very Superior"). Unfortunately, although he had a high IQ, he could no longer employ that intelligence, intelligently. On the other hand, he was no longer depressed, which is one of the many reasons that frontal lobotomies became such a popular in-office psychiatric procedure during the 1940s and 1950s. Frontal lobe patients also may have difficulty thinking up or considering alternative problem solving strategies and thus developing alternative lines of reasoning. For example, Nichols and Hunt (1940) dealt a patient five cards down including the ace of spades which always fell to the right on two successive deals and then to the left for two trials. The patients task was to learn this pattern and turn up the ace. The patient failed to master this after 200 trials. Some frontal lobe patients may also have extreme difficulty sorting even common everyday objects according to category (Rylander, 1939; Tow, 1955), for example, sorting and grouping drinking containers (glasses) with other drinking containers (mugs), tools with tools, etc. Similarily, they may have difficulty performing the Wisconsin Card Sorting Task (Crockett et al., 1986; Drewe, 1974; Milner, 1964, 1971) which involves sorting geometric figures according to similarity in color, shape, or number. However, the manner in which a patient fails on this task is dependent on the locus and laterality of the damage. For example, patients with orbital damage seem to have relatively little difficulty performing this category sorting task (Drewe, 1974; Milner, 1971). Similarly, patients with right frontal damage, although they show a tendency to make perseverative type errors (i.e. persisting in a choice pattern which is clearly indicated as incorrect), perform significantly better than those with left frontal damage (Drewe, 1974; Milner, 1964, 1971). Thus overall, patients with left medial and convexity lesions perform most poorly, and have the greatest degree of difficulty thinking in a flexible manner or developing alternative response strategies. I.Q. Testing A number of studies of conceptual functioning have been performed before and after surgical destruction of the frontal lobes. Although in some cases, such as D.F., described above, the IQ remains high, performance is so uneven and there is so much intertest variability that it is apparent that patients have suffered significant declines (Petrie, 1952; Smith, 1966). In studies in which patients undergoing frontal leucotomy for intractable pain were administered the Wechsler Intelligence Scales both pre- and post surgery, a 20 point drop in the IQ was reported (Koskoff, 1948, cited by Tow, 1955). Likewise, in cases where the Raven's Progressive Matrices or Porteus Mazes were administered both before and after lobotomy, significant declines in intellectual functioning have been documented (Petrie, 1952; Porteus & Peters, 1947; Tow, 1955). As with most tests, the usual pattern is to improve with practice. Hence, these results (and those mentioned above) indicate that frontal lobe damage disrupts abstract reasoning skills, verbal-nonverbal pattern analysis, learning and intellectual ability, as well as the capacity to anticipate the consequences of one's actions or to profit from experience. However, the effects of frontal damage on IQ is dependent on the locus of the damage. For example, left frontal patients show lower Wechsler IQs than those with right frontal lesions (Petrie, 1952; Smith, 1966). In fact, 17 of 18 patients with left frontal damage reported by Smith (1966) scored lower across all subtests compared to those with right frontal lesions. Indeed, patients with left sided destruction perform as poorly as those with bilateral damage (Petrie, 1952). In analyzing subtest performance, Smith (1966) notes that left frontal lobotomy patients scored particularly poorly on Picture Completion (which requires identification of missing details). This is presumably a consequence of the left cerebral hemisphere being more conerned with the perception of details (or parts, segments) vs wholes (chapters 10, 11). Petrie (1952), however, reports that performance on the Comprehension subtests (i.e. judgment, common sense) was most significantly impaired among left frontals. In contrast, individuals with severe right frontal damage have difficulty performing Picture Arrangement--often leaving the cards in the same order in which they are laid (McFie & Thompson, 1972). This may be a consequence of deficiencies in the capacity to discern social-emotional nuances, a function at which the right hemisphere excels (chapter 10). Nevertheless, since so few studies have been conducted it is probably not reasonable to assume that lesions lateralized to the right or left frontal lobe will always effect performance on certain subtests, particularly if there is a mild injury. It is also important to consider in what manner lateralized effects on IQ may be contributing to or secondary to reduced motivation and apathy since bilateral and left frontal damage often give rise to this constellation of symptoms. If the patient is apathetic they are not going to be motivated to perform at the best of their ability. The frontal lobes serve as the "Senior Executive" of the brain and personality, acting to process, integrate, inhibit, assimilate, and remember perceptions and impulses received from the limbic system, striatum, temporal lobes, and neocortical sensory receiving areas (Fuster 1997; Joseph 1986a; Koechlin et al., 1999; Milner and Petrides 1984; Passingham 1993; Selemon et al. 1995; Shallice and Burgess 1991; Stuss 1992; Stuss and Benson 1986; Strub and Black 1993; Van Hosen et al., 1996). Through the assimilation and fusion of perceptual, volitional, cognitive, and emotional processes, the frontal lobes engages in decision making and goal formation, modulates and shapes character and personality and directs attention, maintains concentration, and participates in information storage and memory retrieval (Dolan et al., 1997; Joseph, 1986a, 1988a, 1999a; Kapur et al., 1995; Passingham, 1997; Posner & Raichle, 1994; Tulving et al., 1994). The frontal lobes are not a homologous tissue, and each frontal region is concerned with somewhat different as well as overlapping functions. However, the frontal lobes are clearly functionally laterlized, with a specific spectrum of disorders and functions classically associated with and mediated by the right hemisphere and right frontal lobes, and a different spectrum associated with the left frontal regions. For example, reduced speech output, Broca's aphasia, apathy, "blunted" schizophrenia and major depression are often associated with left lateral (and bilateral) frontal injuries (Bench et al., 1995; Benes, McSparren, and Bird, 1991; Buchsbaum et al. 1998; Carpenter et al. 1993; Casanova et al. 1992; Curtis et al. 1998; d'Elia and Perris 1973, Goodglass & Kaplan, 1999; Hillbom 1951; Perris 1974; Robinson and Downhill 1995; Sarno, 1998). By contrast, impulsiveness, confabulatory verbosity, grandiosity, and mania are often produced by right frontal (as well as bilateral) lesions (Bogousslavsky et al. 1988; Clark and Davison 1987; Cohen and Niska 1980; Cummings and Mendez 1984; Forrest 1982; Girgis 1971; Jack et al. 1983; Jamieson and Wells 1979; Joseph 1986a, 1988a, 1999a; Lishman 1973; Miller et al. 1986; Oppler 1950; Robinson and Downhill 1995; Rosenbaum and Berry 1975; Starkstein et al. 1987; Stern and Dancy 1942; Stuss and Benson 1986). Moreover, as the right frontal lobe is associated with the expression of emotional melodic speech injuries to this area can also produce pressured and/or confabulatory speech that may be melodically distorted. Thus, where with left frontal injuries patients may seem apathetic, indifferent, and/or severely depressed and psychotic if not schizophrenic, right frontal injuries are associated with manic-like disinhibited states, including waxing and waning abnormalities associated with manic-depression. Patient's may become so disinhibited they develop the classic "frontal lobe personality," and become disinhibited, hyperactive, euphoric, extroverted, labile, overtalkative, and may develop perseveratory tendencies (Butter 1969; Butter et al. 1970; Greenblatt 1950; Joseph 1999a; Kennard et al. 1941; Kolb et al. 1974; Malloy, Birhlr, and Duffy 1993; Reitman 1946 1947; Ruch and Shenkin 1943). Patients may become so disinhibited, delusional, grandiose, and emotionally labile that they develop what has classically been described as mania. By contrast, with a left frontal lesion, rather than a loss of emotional control, there is a loss of emotion, and the patient will become severely apathetic, indifferent, and with massive lesions unresponsive, though classically left frontal injuries are associated with depression. These right and left frontal differences are a function of lateralized differences in the control over arousal. Whereas the orbital frontal lobes contraol limbic arousal, the right and left frontal lobes contraol neocortical arousal, with the right frontal lobe exerting bilateral inhibitory and excitatory influences, whereas the left frontal lobe exerts unilateral excitatory influences. MANIA When the right orbital and/or right lateral convexity are damaged, behavior often becomes inappropriate, labile, and disinhibited. Individuals may become hyperactive, distractable, hypersexual, tangential, delusional, and confabulatory (Bogousslavsky et al. 1988; Clark and Davison 1987; Cohen and Niska 1980; Cummings and Mendez 1984; Joseph,1986a, 1988a, 1999a; Lishman 1973; Robinson and Downhill 1995; Starkstein et al. 1987). Although laughing and joking one moment, these same patients can quickly become irritated, angered, enraged, destructive, or conversely tearful and depressed with slight provocation. That is, the patient may present with manic-depressive symptoms, with mania predominating. Hence, manic-depression (bipolar affective disturbances) may be due to waxing and waning abnormalities involving the right and left frontal lobes. Mania and manic-like features have been reported in many patients with injuries, tumors, and even seizures involving predominantly the frontal lobe and/or the right hemisphere (Bogousslavsky et al. 1988; Clark and Davison 1987; Cohen and Niska 1980; Cummings and Mendez 1984; Forrest 1982; Girgis 1971; Jack et al. 1983; Jamieson and Wells 1979; Joseph 1986a, 1988a, 1999a; Lishman 1973; Miller et al. 1986; Oppler 1950; Robinson and Downhill 1995; Rosenbaum and Berry 1975; Starkstein et al. 1987; Stern and Dancy 1942). One frontal patient described as formerly very stable, and a happily married family man, became excessively talkative, restless, grossly disinhibited, sexually preoccupied, extravagantly spent money and recklessly purchased a business which soon went bankrupt (Lishman 1973). In another case, a 46-year old woman was admitted to the hospital and observed to be careless about her person and room, and incontinent of urine and feces. She slept very little and acted in a hypersexual manner. Her symptoms had developed several months earlier when she began accusing a neighbor of taking things she had misplaced. She also would confront him and strip off her clothes. She began going about in just a slip and bra, and informed people she was descended from queens, was fabulously wealthy, and that many men wanted to divorce their wives and marry her. During her hospitalization she was frequently quite loud, disoriented to time and place, and extremely tangential, jumping from subject to subject. After several years she died and a meningioma involving the orbital surface of the right frontal lobes was discovered (Girgis 1971). I have examined 19 male and five female patients who developed mania after suffering a right frontal stroke or trauma to the right frontal lobe. All but four of the males had good premorbid histories and had worked steadily at the same job for over 3-5 years (e.g. Joseph, 1986a, 1988a). Following their injuries all developed delusions of grandeur, pressured speech, flight of ideas, decreased need for sleep, indiscriminant financial activity or irresponsibility, emotional lability, and increased libido, including, in one case, persistent sexual overtures coupled with genital exposure, to the patient's sisters and mother. One formerly very conservative engineer with over 20 patents to his name suffered a right frontal injury when he fell from a ladder. He became sexually indiscriminate and reportedly patronized up to 3 prostitutes a day, whereas before his injury his sexual activity was limited to once weekly with his wife. He also spent money lavishly, suffered delusions of grandeur, camped out at Disney Land and attempted to convince personnel to fund his ideas for a theme park on top of a mountain, and at night had dreams where the Kennedy's would appear and offer him advice --and he was a republican!
  • DISINHIBITED SEXUALITY In some cases following frontal lobe damage patients may engage in inappropriate sexual activity (Benson and Geschwind 1971; Brutkowski 1965; Freeman and Watts 1942, 1943; Girgis 1971; Leutmezer et al., 1999; Lishman 1973; Miller et al. 1986; Strom-Olsen 1946; Stuss and Benson 1986). One patient, after a right frontal injury began patronizing up to 4 prostitutes a day, whereas his premorbid sexual activity had been limited to Tuesday evenings with his wife of 20 years (Joseph 1988a). Another patient with a right frontal stroke propositioned nurses and would spontaneously reach out and fondle large breasted women (Joseph 1988a). It is not unusual for a hypersexual, disinhibited frontal lobe injured individual to employ force. One individual who was described as quite gentle and sensitive prior to his injury, subsequently raped and brutalized several women. Similar behavior has been described following lobotomy. As stated by Freeman and Watts (1943, p. 805): "Sometimes the wife has to put up with some exaggerated attention on the part of her husband, even at inconvenient times and under circumstances which she may find embarrassing. Refusal, however, has led to one savage beating that we know of, and to an additional separation or two" (p. 805). Curiously, in these situations Freeman and Watts (1943, p. 805) have suggested that "spirited physical self-defense is probably the best strategy of the woman. Her husband may have regressed to the cave-man level, and she owes it to him to be responsive at the cave-women level. It may not be agreeable at first, but she will soon find it exhilarating if unconventional." Seizure activity arising from the deep frontal regions have also been associated with increased sexual behavior, including sexual automatisms, exhibitionism, gential manipulation, and masturbation (Leutmezer et al., 1999; Spencer, Spencer, Williamson, & Mattson 1983; Williamson, et al., 1985). One young man that I evaluated and who was subsequently found, with depth electrode recording, to have seizures emitting from the right frontal lobe, had been arrested over 7 times for exposing himself in public. His parents complained that he would sometimes walk around the house grabbing and exposing his genitals, and would sometimes even pee on the floor. In fact, while I was evaluating him as he lay in bed at the Yale Seizure Unit (VAMC) he suffered a seizure which involved the following sequence. He grunted loudly and his left arm shot out in a lateral arc. His left hand then returned to his body and he began to fiddle with the buttons of his pajamas continuing in a downward motion until he reached his penis which he then took in his hand and began to squeeze. As I looked on, he suddenly began to urinate and with such force that I was nearly sprayed with urine. Fortunately, I deftly escaped by leaping to the side and against the wall which put me well out of his range. By contrast, a young woman I examined with right frontal-temporal seizures would spread her legs and engage in pelvic thrusting, coupled with grunting, lip licking and tongue protrusion. Currier et al., (1971), have also reported pelvic thrusting and moaning, and sex appropriate vocalizations, with temporal lobe seizures. However, according to Leutmezer et al., (1999) and as based on prolonged scalp-EEG monitoring, sexual automatisms, such as "sexual hypermotoric pelvic or truncal movements are common in frontal lobe seizures," whereas "discrete genital automatisms, like fondling and grabbing the genitals are more common in seizures involving the temporal lobe." Presumably, the results of Leutmezer et al., (1999) differ from that of Currier, et al., (1971), Joseph (1988a, 1999a), Spencer et al., (1983), and Williams et al., (1985), due to their use of scalp rather depth electrodes which are more sensitive and exacting. On the other hand, temporal lobe/hippocampal sclerosis and atrophy were also documented in the Leutmezer et al. (1999) study. Nevertheless, given the close functional association between the frontal and temporal lobes, and the fact that even a frontal seizure can propagate to the amygdala and thus involve the temporal lobe, perhaps the dysfunctional differences in abnormal sexual behavior are due to seizure origin and the subsequent spread of seizure activity. Indeed, insofar as the behavior involves fondling and grabbing, the hands are being employed, and the hands are generally represented along the medial walls, within the SMA, cingulate, and along the lateral surface of the frontal lobe (see below), whereas truncal movements are more the province of the striatum with which the amygdala is intimately interconnected. Indeed, even with complete destruction of the anterior temporal lobe human and non-human primates may fondle their genitals and masturbate--a common components of the Kluver-Bucy syndrome (see chapter 13). However, as the amygdala has been removed bilaterally, then this part of the brain cannot be directing hand-movements toward the genitals, which thus implicates the frontal lobes. Although this issue cannot be resolved here, it is nevertheless rather obvious than frontal-temporal seizures can produce abnormal and/or inappropriate sexual behavior. There is also some evidence for functional laterality in regard to sexual automatisms and abnormal sexual behavior. In most instances, "sexual" seizures are associated with right frontal seizure foci (Joseph 1988a; Spencer et al. 1983). However, patients may also become hyposexual (Greenblatt 1950; Miller et al. 1986), especially with left frontal injuries, and/or experience genital pain with left temporal seizures (Leutmezer et al., 1999).
  • As detailed below, abnormalities of and damage to the frontal lobes (vs the temporal lobe vs the striatum), can produce signature symptomology. In some cases it is possible to localize a specific subtype of schizophrenia, mania, or depression, to a specific region of the brain based upon those symptoms. Consider, for example, deficits in sacadic eye movements. Smooth pursuit and sacadic eye movements are mediated by the frontal eye fields (Braun, Boman, & Hotson, 1996; MacAvoy et al. 1991) in conjunction with the striatum, midbrain, and cerebellum. Likewise, frontal lobe deficits and reduced ability to perform frontal lobe tests such as the Wisconsin Card Sort, have been found among "Schizophrenics" with smooth pursuit and sacadic abnormalities (O'Discoll, et al. 1995; Rosse et al. 1993), whereas deficits in volitional eye movements have also been documented among those diagnosed with autism (Minshew et al., 1999)--a disorder which shares certain features with schizophrenia. Of course, localization of pathology should be based on the entire constellation of behavioral and cognitive abnormalities, for collectively they may instead indicate a temporal rather than a frontal lobe injury, or both, and/or widespread reduction in gray matter density, increased ventricular volume, and so on (e.g. Gur et al. 1998; Harrison, 1999; Salisbury et al. 1998; Zipurksy et al. 1998). Unfortunately, psychiatric patients tend to be studied as a group based on a DSM-diagnosis, and with few exceptions (e.g. McGuire et al. 1998) are seldom selected on the basis of similarities in signature symptomology. Moreover, because the frontal lobes receive converging input from all limbic system structures, the striatum, as well as the primary and association sensory receiving areas, in some instances deficits associated with frontal injury can be produced secondary to abnormalities in these tissues due to disconnection or abnormal activity. This has given rise to considerable confusion and a lack of consensus. Consider, for example, schizophrenia. Whereas one group of investigators will find evidence of left frontal dysfunction or bilateral gray matter reductions, yet another will report an association with temporal lobe, or ventricular, or striatal abnormalities, whereas yet others will fail to find any clear cut associations at all (reviewed in Harrison, 1999). In consequence, there is little or no consensus as to the neurological foundations of these and other neuropsychiatric disorders, other than the fact that the brain has in some manner been compromised. Moreover, because the frontal lobes are not a homologous structure but maintain extensive interconnections with a variety of brain regions, sometimes damage to the pathways linking the frontal lobes with these areas, or injuries to these "non-frontal" tissues, can produce similar symptoms. For example, the caudate, putamen, and nucleus accumbens (striatum) are located in the paramedian depths of the right and left frontal lobe, and obsessive-compulsions have frequently been observed not only with frontal injuries, but in association with striatal abormalities as based on structural (Calabrese, et al. 1993; Robinson, et al. 1995) and functional studies (Perani et al. 1995; McGuire et al. 1994). Likewise, "schizophrenia" has been associated not only with left frontal injuries, but with left temporal (Bruder et al., 1999; Kwon et al., 1999) or left frontal-temporal lobe injuries (Harrison, 1999), or with damage to the striatum, or the frontal-striatal or temporal (hippocampal/amygdala)-striatal pathways; for example, as measured by positron-emission tomography (e.g. McGuire et al. 1998), P300 evoked potential amplitude (Bruder et al., 1999; Salisbury et al. 1998) and MRI (Jacobsen et al. 1998; Kwon et al., 1999; Nelson et al. 1998; Shidhabuddin et al. 1998), and depending on the diagnostic criteria employed. However, these tissues are functionally linked. Similarly, mania and confabulatory delusions may be associated with right temporal, right frontal-temporal, and right frontal-parietal dysfunction (Bogousslavsky et al. 1988; Cohen and Niska 1980; Joseph 1986a, 1988a, 1999a; Robinson and Downhill 1995); depending on the diagnostic or research criterion employed as well as the nature of the lesion, e.g. stroke, vs tumor, vs seizure disorder. Again, however, these tissues are linked and often injuries are not always well localized but may compromise adjoining tissues, and even the contralateral frontal lobe--such as due to compression, seizures, etc.. With the caveats in mind, the purpose of this chapter, therefore, is to detail the functional neuroanatomy and to functionally localize and detail the signature symptomology and the clinical psychopathology associated with abnormalities of the different subregions of the frontal lobe and neural pathways including the striatum. Hence, motor functioning, memory, attention, and arousal, schizophenia, depression, mania, catatonia, obsessive compulsions, aphasia, confabulatory delusions, and the "frontal lobe personality" will be discussed. EMOTIONAL & PROSODIC SPEECH Right frontal injuries are thus associated with disinhibited states, including manic neuro-psychosis coupled with disturbances of thought and speech. Although language per se, is not aphasic, speech may be rushed, contaminated with unusual, tangential, and delusional ideas, and in some cases, melodic control over speech appears to be lost, such that the patient's melody of voice may not correspond with or parallel what is being said; e.g. they may be saying one thing, but by their labile tone of voice, seem to be meaning something else altogether. Although language is usually discussed in regard to grammar and vocabulary, it is also emotional, melodic and prosodic --features which enable a speaker to convey and a listener determine, intent, attitude, feeling and meaning (chapters 10, 15). A listener comprehends noy only what is said, but how it is said--what a speaker feels. Feeling and attitude are conveyed through the melody (musical qualities), inflection, intonation, and prosody of one's voice, and by varying the pitch, inflection, timbre, stress contours, melody, as well as the rate and amplitude of speech --capacities predominantly mediated by the right half of the cerebrum (see chapter 10). Patients with severe forms of Broca's expressive aphasia are unable to discourse fluently. However, they may be capable of swearing, making statements of self-pity, praying, singing, and even learning new songs (Gardner 1975; Goldstein 1942; Gorelick and Ross 1987; Joseph 1988a; Ross 1981; Smith 1966; Smith and Burklund 1966; Yamadori, Osumi, Mashuara, and Okuto, 1977)--although in the absence of music they would be unable to say the very words they had just sung. This is because the ability to produce non-linguistic and musical/emotional sounds is mediated by the undamaged right frontal lobe and limbic nuclei (Gardner 1975; Gorelick and Ross 1987; Joseph 1988a; Ross 1993; Shapiro and Danly 1985). Indeed, just as the left frontal convexity (i.e. Broca's area) subserves the syntactical, temporal-sequential, motoric, and grammatical aspects of linguistic expression (Foerster 1936; Fox 1995; Goodglass & Kaplan, 2000; LeBlanc 1992; Petersen et al. 1988, 1989; Sarno, 1998), there is a homologous region within the right frontal area which mediates the expression of emotional and melodic speech (Gorelick and Ross 1987; Joseph 1982, 1988a, 1999a; Ross 1981, 1993; Shapiro and Danly 1985). With massive damage involving the right frontal melodic-emotional speech area, speech may become flat and monotonous, or conversely, the ability to alter or convey melodic and prosodic elements may become exceedingly abnormal and distorted. With extensive injuries to the right frontal lobe, patients may lose control over their voice and at times may sound as if they are crying, wailing, or screeching. Such patients may loose the ability to engage in vocal mimicry or to accurately repeat various statements in an emotional manner (Gorelick and Ross 1987; Joseph 1988a; Ross 1981, 1993). With mild damage, rather than severe distortions or a loss of melody, the intonational qualities of the voice can become mildly abnormal and patients may seem to be speaking with an odd midwestern-like accent--particularly with deep lesions of the right frontal area, perhaps involving the cingulate or basal ganglia. Prosodic distortion in the form of an unusual accent is sometimes seen in seizure disorders involving deep right frontal or frontal-temporal areas. On the otherhand, with left frontal lesions some patients develop what sounds like an unlearned foreign accent, as if they were from Germany, France, etc. (Blumstein et al. 1987; Graff-Radford et al. 1986). This is due, in part, to distortions involving the pronounciation of vowells. When damage is limited to this right frontal emotional-motor speech area, the ability to comprehend and understand prosodic-emotional nuances appears to be somewhat intact (Gorelick & Ross, 1987; Joseph, 1988a; Ross, 1993). However, with right temporal injuries, the ability to comprehend these nuances may be lost (Ross, 1993). It is interesting to note, however, that despite the clinical, neuropsychological, and neuroanatomical evidence indicating that the right frontal and right temporal areas contribute to the production of emotional prosodic melodic speech, that functional imaging and blood flow studies have failed to display significant activity in these regions during language-related activities (Frost, et al., 1999; Pujol, et al., 1999)--a function perhaps, of the insensitivity of the tasks and/or measures employed in this regard. TANGENTIAL, PRESSURED SPEECH & CIRCUMLOCUTORY SPEECH Patients suffering from mania often display pressure, tangential and delusional speech. Likewise, with bilateral or right frontal lobe damage, speech may become pressured and tangential such that the patient rapidly diverges to other and unrelated topics (Joseph, 1986a, 1988a, 1999a). For example, when a patient with severe right orbital damage was asked if his injury affected his thinking, he replied, "yeah--it's affected the way I think--It's affected my senses--the only thing I can taste are sugar and salt--I can't detect a pungent odor--ha ha--to tell you the truth it's a blessing this way" (Blumer & Benson, 1975, p.197). One frontal patient when asked what he received for Christmas replied, "I got a record player and a sweater." (Looking down at his boots) "I also like boots, westerns, popcorn, peanuts and pretzels." Another right frontal patient when asked in what manner an orange and a banana were alike replied, "fruit. Fruitcakes--ha ha--tooty fruity." When asked how a lion and a dog were alike he responded, "They both like fruit--ha ha. No. That's not right. They like trees--fruit trees. Lions climb trees and dogs chase cats up trees, and they both have a bark." Tangentiality is in some manner related to impulsiveness as well as circumlocution. In contrast, patients with circumlocutious speech often have disturbances involving the left cerebral hemisphere and frequently suffer from word finding difficulty and sometimes receptive or expressive dysphasia. They experience difficulty expressing a particular idea or describing some need as they have trouble finding the correct words. Thus talk around the central point and only through successive approximations are able to convey what they mean to say. Patients with tangential speech lose the point altogether. Instead, words or statements trigger other words or statements which are related only in regard to sound (e.g. like a clang association) or some obscure and ever shifting semantic category. Speech may be rushed or pressured and the patient may seem to be free associating as they jump from topic to topic. Hence, in contrast to the aphasia, or speech arrest associated with left frontal injuries, right frontal lesions may result in speech release ("motor mouth"). Speech becomes disinhibited, pressure, and contaminated with tangential associations, and the patient may seem to be free associating as they jump from topic to topic. In the extreme speech becomes filled with confabulatory ideas. THE LEFT FRONTAL LOBE: DEPRESSION, APATHY, APHASIA, SCHIZOPHRENIA BROCA'S EXPRESSIVE APHASIA Broca's speech are is located in the general vicinity of the posterior- inferior region of the left frontal area (i.e. third frontal convolution), and includes portions of areas 45, 6, 4, and all of area 44. This region is multimodally responsive (Passingham, 1997) and receives projections from the auditory, visual, somesthetic areas (Geschwind, 1965; Jones & Powell, 1970), as well as massive input from the inferior parietal lobule and Wernicke's area via a rope of nerve fibers referred to as the arcuate fasciculus (which also links these areas to the amygdala). In addition, Broca's area receives fibers from and projects to the anterior cingulate as well as the brainstem periaqueductal gray which subserves vocalization. Broca's speech area is a final converging destination point through which thought and other impluses come to receive their final sequential (syntactical, grammatical) inprint so as to become organized and expressed as temporally ordered motoric articulations; i.e. speech (Foerster 1936; Fox 1995; Goodglass, 1993; Goodglass & Kaplan, 2000; Kimura, 1993; LeBlanc 1992; Petersen et al. 1988, 1990; Sarno, 1998). Verbal communication, the writing of words (via transmission to Exner's area), and the expression of thought in linguistic form is made possible via Broca's area which programs the adjacent oral-laryngeal musculature as represented within the adjacent primary motor areas (Foerster 1936; Fox 1995; Kimura, 1993; LeBlanc 1992; Petersen et al. 1988, 1990; Sarno, 1998); and which transmits to Exner's writing area so that words may be written. The importance of Broca's area and the left frontal lobe has also been demonstrated through functional imaging. For example, the left frontal lobe becomes activated during inner speech and subvocal articulation (Paulesu, et al., 1993; Demonet, et al., 1994). The left frontal lobe also becomes highly active when reading concrete and abstract words (Buchel et al., 1998; Peterson et al., 1988), and when engaged in semantic decision making tasks (Demb et al., 1995; Gabrielli et al., 1996). Moreover, activation increases as word length increases and in response to long and umfamiliar words (Price, 1997). With injuries to Broca's area the individual loses the capacity to produce fluent speech (Goodglass, 1993; Goodglass & Kaplan, 2000; Sarno, 1998). Output becomes extremely labored, sparse, and difficult, and they may be unable to say even single words, such as "yes" or "no". Often, immediately following a large stroke patients are almost completely mute and suffer a paralysis of the upper right extremity as well as right facial weakness (since these areas are neuronally represented in the immediately adjacent area 4). Patients are also unable to write, read out loud or repeat simple words. Interestingly, it has been repeatedly noted that almost immediately following stroke some patients will announce "I can't talk", and then lapse into frustrated partial mutism. With less severe forms of Broca's (also referred to as expressive, motor, nonfluent, verbal) aphasia, speech remains labored, agrammatical, fragmented, extremely limited to stereotyped phrases ("yes", "no", "shit", "fine") and contaminated with syntactic and paraphasic errors i.e. "orroble" for auto, "rutton" for button (Bastiaanse, 1995; Goodglass, 1993; Goodglass & Kaplan, 1999; Haarmann & Kolk 1994; Hofstede & Kolk 1994; Levine & Sweet, 1982, 1983; Sarno, 1998; Tramo et al. 1988). Writing remains severely effected, as are oral reading and repetition. Such patients also have mild difficulties with verbal perception and comprehension (Hebben, 1986; Maher et al. 1994; Tramo et al., 1988; Sarno, 1998; Tyler et al. 1995), including the ability to follow 3-step commands (Lura 1980). Commands to purse or smack the lips, lick, suck, or blow are often, but not always, poorly executed (DeRenzi et al. 1966; Kimura 1993); a condition referred to as bucal-facial apraxia. Non-speech oral movements are seldom significantly effected (Goodglass & Kaplan, 1999; Hecaen & Albert, 1978; Kimura 1993; Levine & Sweet, 1983). With mild damage, patients may demonstrate severe confrontive naming and word finding difficulties (anomia), as well as possible right facial, hand, and arm weakness. Speech is often characterized by long pauses, misnaming, paraphasic disturbances and articulatory abnormalities (Goodglass, 1993; Goodglass & Kaplan, 1999; Sarno, 1998). Stammering and the omission of words may also be apparent. Similarly, electrical stimulation of this region results in speech arrest (Ojemann & Whitaker, 1978; Lesser et al., 1984) and can alter the ability to write and/or perform various oral-facial movements. It is noteworthy that even with anterior lesions or surgical frontal lobectomy sparing Broca's area a considerable impoverishment of spontaneous speech can result (Luria, 1980; Milner, 1971; Novoa & Ardila, 1987). Disturbances involving grammar and syntax, and reductions in vocabulary and word fluency in both speech and writing have been observed with frontal lesions sparing Broca's area (Benson, 1967; Crockett, Bilsker, Hurwitz, & Kozak, 1986; Goodglass & Berko, 1960; Milner, 1964; Novoa & Ardila, 1987; Petrie, 1952; Samuels & Benson, 1979; Stuss, et al., 1998; Tow, 1955). In word fluency tests, however, simple verbal generation (e.g. all words starting with L) is usually more severely impaired than semantic naming, e.g. all animals which live in the jungle--which is presumably a function of semantic processing being more dependent on posterior language areas (Stuss et al., 1998). DEPRESSION, APHASIA, & APATHY Depression, "psycho-motor" retardation, apathy, irritability, and blunted mental functioning are associated with neocortical injuries of the left lateral and medial frontal lobe. When Broca's area has been injured, patients not only have difficulty with expressive speech (Bastiaanse 1995; Goodglass and Kaplan 1999; Haarmann and Kolk 1994; Hofstede and Kolk 1994; Sarno, 1998) but they typically become exceedingly frustrated, irritable, and depressed (Gainnoti 1972; Robinson and Benson 1981; Robinson and Szetela 1981; Robinson and Downhill 1996). In large part, depression is common with Broca's aphasia as patients are painfully aware of their deficit (Gainotti 1972; Joseph, 1988a). Indeed those with the smallest frontal convexity lesions often become the most depressed (Robinson and Benson 1981). Depression in these cases appears to be a normal reaction and as such is mediated by undamaged tissue; i.e., the right hemisphere which is dominant for emotional expression and perception (e.g. Borod 1992; Cancelliere and Kertesz 1990; Freeman and Traugott 1993; Heilman and Bowers 1996; Joseph 1988a; Van Strien and Morpurgo 1992). That is, the right hemisphere being emotionally astute, reacts appropriately to the patient's condition and becomes depressed. If fact, with the exception of at least one study (Mayberg et al., 1999) almost all other studies demonstrate increased right frontal activity in response to negative moods (Rauch et al., 1996; Shin et al., 1997, 1999; Teasdale et al., 1999) and decreased left frontal activity with depression (Bench et al., 1995). In fact, repetitive transcranial magnetic stimulation of the right frontal lobe reduces depressive symptoms (Klein et al., 1999), whereas left frontal activity increase with the alleviation of depression as demonstrated through functional imaging studies (Bench et al., 1995). Not only are left frontal injuries associated with tearfulness, irritability, and depression (where it is the right which may actually feel sad), but psychiatric patients classified as depressed, and normal individuals made to feel severely depressed, demonstrate insufficient left frontal activation and arousal (d'Elia and Perris 1973, Perris 1974; Tucker et al. 1981). For example, reduced bioelectric arousal over the left frontal region has been reported following depressive mood induction (Tucker et al. 1981). Similarly depressed mothers and depressed children show reduced left relative to right frontal activation (reviewed in Dawson 1994). With recovery from depression left hemisphere arousal returns to normal levels. Likewise, Patients who are severely depressed have been shown to demonstrate insufficient activation and a significant lower integrated amplitude of the EEG evoked response over the left vs right frontal lobe (d'Elia and Perris 1973, Perris 1974). Based on EEG and clinical observation, d'Elia and Perris have argued that the involvement of the left hemisphere is proportional to the degree of depression. Moreover, with recovery the amplitude of the evoked response increases to normal left hemisphere levels. Functional imaging of depressed states indicates reduced activity in the left frontal lobe and anterior cingulate (Bench, et al,., 1992) and when these individuals ceased to be depressed, activity levels increases (Bench et al., 1995). Left frontal lobe depression is therefore seen in those who are aphasic, and those whose depression has been long standing or even recently provoked. The more severe the depression, the greater is the reduction in left frontal functioning (whereas with mild transient sadness there might be a reduction in right frontal activity). Hence, with massive left frontal dysfunction, including even when Broca's area is spared, patient may become exceeding depressed, apathetic , hypoactive and indifferent (Robinson et al. 1984; Robinson and Szetela 1981; Sinyour, et al. 1986). However, with severe injuries, instead of worried or emotionally depressed, the patient instead is indifferent, uncaring, apathetic, and emotionally blunted (Blumer and Benson 1975; Freeman and Watts 1942, 1943; Girgis 1971; Hecaen 1964; Luria 1980; Passingham 1993; Stuss and Benson 1986; Strom-Olsen 1946). One patient who "prior to his accident requiring amputation of the left frontal pole, had been garrulous, enjoyed people, had many friends, was active in community affairs" and had "true charisma... became quiet and remote, spent most of his time sitting alone smoking, and was frequently incontinent of urine, and occasionally of stool. He remained unconcerned and was frequently found soaking wet, calmly sitting and smoking. When asked, he would deny illness" (Blumer and Benson 1975, p. 196). Similarly, inertia and apathy usually imediately follow surgical destruction or injury of the frontal lobes, the left frontal lobes in particular (Hillbom 1951; Lishman 1968). "The previously busy housewife who has always been a dirt-chaser, and who has kept her fingers perpetually busy with darning, crocheting, knitting, and so on, sits with her hands in her lap watching the 'snails whiz by'. Like a child she must be told to wipe the dishes, to dust the sideboard, to sweep the porch" and even then the patient completes only half the task as there is no longer any interest or initiative (Freeman and Watts 1943, p. 803). In some cases the apathy is so profound that "whoever has charge of the patient will have to pull him out of bed, otherwise he may stay there all day. It is especially necessary since he won't get up voluntarily even to go to the toilet" (p. 802). Depressive-like features, however, also seem to result with left anterior damage sparing Broca's area such as when the frontal pole (of either hemisphere is compromised (Robinson et al. 1984; Robinson & Szetela, 1981; Sinyour, et al. 1986). As described by Kennard (1939) monkeys with bilateral frontal lobe damage would sit with their head sunk between their shoulders, neither blinking or turning their heads in response to noise, threats or the presence of intruders; but would stare absently straight ahead with no facial expression. In a similar study, following massive frontal destruction a monkey who was formerly quite active and the dominant leader of his group became inactive, indifferently watched others, failed to respond emotionally, and seemed to have lost all interest and ability to engage in complex social behavior (Batuyev, 1969). In his summary of two large scale frontal tumor studies Hecaen (1964) noted the majority seemed confused, disorganized, apathetic, hypoactive, and suffering from inertia and feelings of indifference.However, puerility was also common among these patients and many demonstrated decreased judgment with either total or partial unawareness of the environment. In some, this initial state of inertia disappears, whereas in others it becomes a lasting or even progressively severe disturbance. "The previously busy housewife who has always been a dirt-chaser, and who has kept her fingers perpetually busy with darning, crocheting, knitting, and so on, sits with her hands in her lap watching the 'snails whiz by'. Like a child she must be told to wipe the dishes, to dust the sideboard, to sweep the porch" and even then the patient completes only half the task as there is no longer any interest or initiative (Freeman & Watts, 1943, p. 803). In part, depression coupled with apathy secondary to frontal injuries is probably related to damage to the interconnections with the medial region, an area which when damaged induces hypokinetic and apathetic states (see below). However, these latter patients are not depressed, but rather severly apathetic, indifferent, hypoactive, and poorly motivated. When questioned, rather than worried or truly concerned about their condition the overall picture is that of confusion, disinterest, and blunted emotionality (Freeman & Watts, 1942: Hacaen, 1964) i.e. there is a lack of worrisome thoughts or depressive ideation. Hence, in part, apathetic and depressive features may result from left frontal convexity and frontal pole damage due to a severance of fibers which link emotional impulses (such as those being transmitted via the orbital and medial region) with external sources of input or cognitive activity which are transmitted to the convexity (i.e. disconnection), impulses which are transmitted from the medial frontal lobes to the orbital, superior, and anterior frontal lobes. Through these interconnections, emotional impulses arising in the limbic system, can be transmitted through the medial frontal lobes to the lateral frontal lobes, where they then become ideas. Or conversely, neocortical cognitions may be transmitted from the lateral neocortical surface to the medial areas where they are integrated to again become emotional ideas. It was the recognition that the frontal lobes acted as a bridge between emotion and idea which led to the wide scale use of frontal lobotomy; i.e. surgical destruction of inter-linking fibers --a technique, which when used in the 1940s and 1950s, often involved little more than blindly swishing a "surgical ice pick" inside somebody's brain! Moreover, convexity lesions, like medial damage, may result in a disconnection not only between cognitive-perceptual and emotional activity, but would prevent limbic system output from reaching the motor areas such that emotional-motivational impulses are unable to become integrated with motor activities. The patient is thus motorically hypo-emotionally aroused (i.e. depressed), and appears to be demonstrating psychomotor retardation. Just as left frontal convexity motor damage can result in left sided apraxia (due to right hemisphere disconnection from left parietal temporal-sequential output), the reverse can also occur. That is, with left frontal damage, linguistic impulses not only fail to become expressed, but emotional output from the right hemisphere and limbic system fail to become integrated with linguistic-ideation (i.e. thought). Ideas no longer come to be assigned emotional significance. In the extreme the motivational impetus to even engage in thought production is cut-off. As pertaining to laterality, left frontal (vs. right) lesions are associated with reductions in intellectual and conceptual capability which often leads to confusion and a reduced ability to appreciate and appropriately respond to the external or internal environment. In these instances, one possible consequence is apathy, indifference, hyporesponsiveness, and depressive-like symptoms. On the otherhand, it is possible that among psychiatric patients and otherwise normal, albeit, depressed individuals, that the left frontal region appears relatively inactive because the right frontal area is preoccupied with being depressed; the right frontal region is excessively aroused (Teasdale, et al., 1999). That is, excessive right frontal arousal leads to massive left frontal inhibition; i.e., the bilateral arousal system of the right hemisphere inhibiting the left. THE LEFT LATERAL FRONTAL LOBE & STRIATUM: SCHIZOPHRENIA PSYCHOSIS & BLUNTED (NEGATIVE) SCHIZOPHRENIA Patients with left frontal injuries or dysfunction, and who become unresponsive, apathetic, untidy, and whose speech is abnormal, are sometimes characterized as suffering from an emotionally blunted form of schizophrenia. In fact, left lateral as well as bilateral convexity abnormalities are often associated with apathetic, blunted, and "negative" forms of schizophrenia (Buchsbaum 1990; Carpenter et al. 1993; Casanova et al. 1992; Weinberger 1987; Wolkin et al. 1992). Similarly, patients classified as schizophrenic have also been reported to demonstrate abnormal left( or bilateral) frontal lobe EEG's indicative of hypoarousal (Akbarian et al. 1993; Ariel et al. 1983; Ingvar and Franzen 1974; Kolb and Whishaw 1983; Levin 1984). Lateral frontal gray matter and brain volume reductions and decreased activity have been repeatedly noted (Andreasen et al. 1990; Buchanan et al. 1998; Curtis et al. 1998), including decreased blood flow (Weinberger et al. 1986) hypoactivity (Wolkin et al. 1992), reduced metabolism (Buchsbaum et al. 1992), as well as left sided abnormalities affecting the striatum (Breier et al. 1992; Buchanan et al. 1993; Swayze et al. 1992) which is buried within the depths of the frontal lobe. This is not to imply that all subtypes of "schizophrenia" are secondary to frontal lobe pathology. The left temporal lobe have also been implicated as measured by positron-emission tomography (e.g. McGuire et al. 1998), P300 evoked potential amplitude (Bruder et al., 1999; Salisbury et al. 1998) and MRI (Jacobsen et al. 1998; Shidhabuddin et al. 1998; Kwon et al., 1999). However, as the temporal lobes are implicated in these subtypes of schizophrenia, the pattern of symptoms differs from those with left frontal dysfunction. For example, depending on if the right vs left and superior vs the inferior temporal lobe are more greatly impacted, patients are more emotional, more verbal, more active, and more likely to suffer visual and auditory hallucinations, coupled with disturbances of comprehension. However, whereas as a superior temporal lobe (Wernicke's area) abnormality can affect the left frontal lobe (Broca's area) thus producing fluent-aphasic speech and thus a complete formal thought disorder, left inferior temporal lobe and amygdala dysfunction can disrupt the orbital and medial frontal lobe including the caudate and putamen. Indeed, the striatum evolved from and is densely interconnected with the amygdala, and if injured mental functioning becomes invariably abnormal. Hence, it appears that only certain subpopulations of schizophrenics actually suffer from frontal lobe dysfunction, such as those with catatonia, posturing, mannerisms, and emotional blunting coupled with reduced speech output and apathy. However, not all "frontal" schizophrenics are blunted, but may display unusual mannerisms and/or a silly, puerile childishness that long ago had been referred to as "Hebephrenia" Indeed, Hillbom (1951), described a number individuals with head trauma and missle wounds to the frontal lobes who developed schizophrenic-like symptoms, including catatonia and hebrephrenia. However, Hillbom (1951) also found that left frontal patients are more likely to develop these symptoms. THE STRIATUM: EMOTION, PLEASURE, BODY LANGUAGE, AND SCHIZOPHRENIA The corpus (caudate and putamen) and limbic striatum (olfactory tubercle, nucleus accumbens, stria innominata) are buried deep within the frontal lobe, with the head of the caudate arising from near the orbital floor and then ascending deep alongside the inner medial and lateral walls (Mink, 1997) The striatal nuclei are thus intimately associated with the orbital, medial and lateral frontal lobes, as well as the amygdala with which they merge in the temporal lobe. It is through these frontal-striatal-amygdala pathways that emotional states come to translated into complex motor acts and expressed through body language (see Figure 5). That is, the striatum mediates facial expression and gesture, and produces ballistic movements, including hitting, kicking, running and biting (Mogenson and Yang 1991; MacLean 1990; Rapoport 1991). Since humans possess basically the same striatum and limbic system, when happy, sad, angry, and so on, the facial and body musculature assumes the same readily identifiable emotional postures and expression regardless of culture or racial orgins (Ekman 1993; Eible-Ebesfedlt 1990; Joseph, 1993). The striatum is capable of considerable flexibility in motor-emotional expression, and is exceedingly responsive to the internal motivational and emotional state. Through its extensive interconnections with the limbic system and the mesolimbic dopamine (DA) system the striatum is able to perceive emotional stimuli and can "experience" pleasure. Striatal neurons selectively respond to motivationally significant stimuli that are rewarding or punishing (Rolls and Williams 1987; Schneider and Lidsky 1981) and can generate feelings of pleasure in reaction to amphetamine, cocaine and opiates (Ellison 1994; Hakan et al. 1994; Koob et al. 1991). Destruction of striatal neurons disrupts the capacity to experience pleasure such as mediated through opiates and cocaine (Koob et al. 1991). Similarly, lesions to the corpus striatum and lenticular nucleus (putamen and globus pallidus) can attenuate one's capacity to experience pleasure or motorically express their emotions via the musculature; e.g. the face and body becomes frozen; a condition similar to Parkinson's disease. In fact, surgical destruction of or chemical lesions to the anterior corpus striatum and surrounding tissue can produce catatonic or "frozen" states, including prolonged posturing where the subjects will remain unmoving for hours, days, and even weeks at a time (Denny-Brown 1962; Spiegel and Szekely 1961). Similar paralytic, petrified disturbances can be induced with dopamine depletion. Indeed, a major function of striatal DA is inhibition (Ellison 1994; Le Moal and Simon 1991; Mercuri et al. 1985), and DA depletion can trigger striatal as well as limbic hyperactivation (chapter 30). If hyperactivated, associated muscular activity as well as the neural pathways linking the striatum with the frontal lobe and amygdala, can be disrupted and overwhelmed, thereby giving rise to emotional and behavior paralysis. The patient may become catatonic (see below) or in the less extreme may demonstrate signs of Parkinson's disease. Likewise, excessive DA, and reduced striatal activity can disrupt all aspects of motor, cognitive and emotional functioning, with some patients developing an acute schizophrenic psychosis (Castellanos et al. 1994; Chakos et al. 1994; Ring et al. 1994; Shihabuddin et al. 1998; Snyder 1972). In addition to reduced activity and metabolism (Buchsbaum, et al. 1992; Resnick et al. 1988; Wiesel et al. 1987), as based on MRI, limbic striatal structures are reduced in size (Shihabuddin et al. 1998) whereas the corpus striatum has been found to be increased in size in schizophrenics vs normal controls (Heckers et al. 1991; Shihabuddin et al. 1998) especially in the left hemisphere (Breier et al. 1992; Buchanan et al. 1993; Swayze et al. 1992). Moreover, as the lateral frontal neocortex is also innervated by striatal as well as DA fibers, reduced DA levels can also negatively impact the lateral frontal lobes as well as the striatum (Beatty et al. 1993). Striatal abnormalities are linked to frontal abnormalities and vice versa. In consequence, if the frontal lobes become abnormal secondary to striatal/DA disturbances, frontal symptoms will be evoked. Hence, striatal dysfunction is also associated with depression, apathy, obsessive compulsive disorders, "schizophrenia," as well as mania (Aylward et al. 1994; Baxter et al. 1992; Caplan, et al. 1990; Castellanos et al. 1994; Chakos et al. 1994; Deicken et al. 1995; Ellison 1994; Rauch et al. 1994; Richfield et al. 1987; Robinson and Downhill 1995), depending on the nature, degree, extent, and laterality of destruction. For example, injuries or abnormalities restricted to the right caudate are more likely to result in a manic-like psychosis (Castellanos et al. 1994; Robinson and Downhill 1995) --similar to right frontal lobe injuries. By contrast, left or bilateral caudate injuries are associated with apathetic states, decreased spontaneous activity, slowed and delayed dysarthric and emotionally flat speech, with some patients responding to questions only after a 20-30 second delay (Caplan et al. 1990; Richfield et al. 1987). For example, Richfield et al. (1987, p. 768) described a 25 year old female honor student, soon to be married, who suddenly disappeared after complaining of headaches and nausea. When found three days later she "had undergone a dramatic personality change manifested by alterations in affect, motivation, cognition, and self-care which included vulgarity, impulsiveness, violent outbursts, enuresis, indifference, hypersexuality, shoplifting and exposing herself. She was inattentive and uninterested in her surroundings. She would frequently lie down to sleep. Her affect was flat." CT-scan indicated bilateral damage to the head of the caudate nuclei as well as surrounding structures. Since the head of the striatum descends ventrally between the lateral and medial walls, injuries to this part of the brain, including DA abnormalities, also disrupts these adjoining tissues. If the right or left lateral walls are injured, patients are likely to appear manic or apathetic, depressed, irritable, and schizophrenic. However, if the medial walls of the frontal lobes are injured, cognitive, motivational, and motor functioning will become profoundly abnormal, and the patient may become completely catatonic.
  • Prefrontal Cortex Area 10 Responsible for planning, structuring, and evaluating voluntary (goal directed behavior, i.e., activities requiring the constant comparison of planned acts with the effects achieved. A. Deficits associated with lesions of the prefrontal cortex With minor lesions Inability to prevent rapid extinction of orienting response following verbal instruction. Disturbances in regulatory role of speech. Disturbances in complicated gnostic functions (e.g. understanding complicated pictures, thematic pictures, comprehension of written text). Problem solving difficulties associated with disturbances in selective organization of mental activity (i.e. serial sevens). Deficits in complex tasks requiring inhibition of habitual behavior patterns. Difficulties with actions requiring a series of movements, less severe when accompanied by external verbalization (Fist, edge, palm). Difficulties in task executions when instructions or prompts conflict with what would be expected, although ability to carry out simple instructions is unimpaired (visual or verbal). Difficulties tapping at successive groups of rhythms or drawing a series of figures that alternate in pattern (tendency to perseverate). Decreased spontaneity, decreased rate of behavior, decreased range of interests, loss of initiative, and impulsiveness without self-corrective action may be early signs. Deficits in visual tracking and scanning, especially on complex tasks. Difficulty in constructing mirror-image relationships, especially if complex. With more extensive lesions. Perseveration: difficulties in making behavioral shifts in attention, movement, and attitude. Concreteness & decreased creativity. Inflexibility in cognitive, perceptual and motor modalities. Poor recall of thematic verbal material (paragraphs). Poor recall of verbal & nonverbal series, with contamination of first & subsequent series. Deficits in comprehension of logical-grammatical (prepositional) constructions (e.g. "place a cross beneath the circle.") . Difficulties in writing associated with fatigue, progressively smaller characters, perseveration, loss of overall plan (i.e. letter transpositions, etc.). Deficits in abstract/categorical intellect. Take longer to learn go-no go tasks and make more false positive responses particularly with medial frontal lesions. Diminished visual scanning and tracking, resulting in impulsive judgments which are based on the perception of a single aspect of a stimulus. Performance of relatively simple task is impaired by perseveration; however, overlearned tasks are conducted without difficulty. Increased level of distractibility, especially to small noises or events. Memory curve plateaus early (approximately 5 items), even with rehearsal. Disturbances in selective memory with confabulation. Defects in time sense with respect to recency and time span Judgments and disturbances of temporal orientation occurring with bilateral frontal lobe lesions. More superior lesions produce motor disturbances, while inferior lesions produce speech disturbances Increased trend toward confabulation . Magnitude of deficit is associated with the cause of the lesion (i.e. surgery or degenerative) and the presence of generalized physical disorders (i.e. hypertension). Also, deficits are more severe with bilateral involvement. Constructive intellectual activity may be distributed when preliminary analysis and formation of a plan is required (not constructional apraxia per se) . Diminished critical self-evaluation of behaviors; no distress or attempts at correction. Able to perform firmly-established verbal analogies (father: son: Mother, but difficulty in forming unfamiliar analogies Poor capacity for arithmetic tasks involving a series of analytic steps, although often able to solve simple problems. Tend to make impulsive judgments. Emotional disturbances seen as two principle reactions: inhibition (apathy, narrowing of interests, flattered affect, withdrawal) and disinhibition (euphoria, impulsivity, irritability, anxiety, obscene language. Symptoms of frontal lobe lesions with increased intracranial pressure can include headache and somnolence. With medial orbital lesions More often associated with emotional changes such as apathy or hyperactivity. Defects in sorting or abstraction tasks usually not observed; gross intellectual changes also not apparent. Olfactory & visual disturbances may occur. Emotional alterations can range from apathy to short-term lability. Lateral dorsal lesions Associated more with intellectual deficits. Perseveration is more common: associated with impaired shifting in attention and thinking. With extensive lesions, gross perseveration may occur even though patient recognizes as inappropriate. Impaired categorical thinking apparent.
  • A. Orbitofrontal Syndrome - Damage in Brodman areas 11, 12 results in prominent affect disturbances. Emotional lability and decreased impulse control contribute to poor social integration. Problems such as loss of control of anger and inappropriate laughing, crying or sexuality are often observed. Attention capacity is usually preserved, frontal release signs (i.e. snout, suck, palmomental reflexes) are absent and the patient is typically aware of the problem but unable to control their reflexive inappropriate behavior. The most common cause of the orbital syndrome is head trauma with contra coup damage. Olfactory groove meningiomas can also present with similar complaints.
  • B. Mesial Syndrome - Bilateral mesial prefrontal damage involving supplementary motor and cingulate cortex (Brodmann areas 24, 25, 32, 33 and mesila 6, 8, 9 ) produces an amotivational, akinetic state with motor programming deficits manifesting clinically as apractic disturbances. Unilateral mesial or mild bilateral disease yields lesser degrees of difficulty in the initiation and sustaining of motor and mental activity. A common cause is anterior cerebral artery infarction due to spasm from subarachnoid hemorrhage.
  • C. Dorsolateral - Damage in dorsolateral prefrontal cortex (Brodmann areas 6, 68, 9, 10, 44, 45, 46) leads to a complex range of behavioral disturbances since this is the most advanced phylogentic area in man. In early disease due either to tumors (i.e. glioma) or degenerative disease (i.e. Picks) sparing language cortex, subtle deficits in creativity and mental flexibility are often noted by the patient or family. As unilateral disease progresses or becomes bilateral pronounced behavioral problems become apparent. Abnormalities emerge in planning, goal directed behavior, temporal coding of external and internal events, metamemory (i.e. confidence about memory judgments), judgment and insight. Attention capacity is invariably impaired in advanced disease. Frontal convexity syndrome (apathetic) Apathy (occasional brief angry or aggressive outbursts common) Indifference Psychomotor retardation Motor perseveration and impersistence Loss of self Stimulus-bound behavior Discrepant motor and verbal behavior Motor programming deficits Three-step hand sequence Alternating programs Reciprocal programs Rhythm tapping Multiple loops Poor word list generation Poor abstraction and categorization Segmented approach to visuospatial analysis LATERAL FRONTAL NEOCORTICAL REGULATION With the exception of olfactory information, which via the olfactory tracts projects to the limbic system and is relayed as well as directly transmitted to the orbital region (Cavada, 1984; Gloor, 1997), all sensory impulses are first transferred to the thalamus before being transmitted to the primary auditory, visual, and somesthetic receiving areas. From the primary zones this information is sent to 3 separate major locations: to the immediately adjacent sensory association area, back to the thalamus, and to the motor cortex of the frontal lobes. The motor area then relays this information to the lateral convexity which simultaneously receives fiber projections from the sensory association areas (Cavada, 1984; Jones et al. 1978; Jones & Powell, 1970; Pandya & Kuypers, 1969) and the inferior parietal lobule. Hence, the frontal cortex and right and left lateral convexity are "interlocked" with the posterior sensory areas via converging and reciprocal connections with the first, second, and third level of modality specific analysis, including the multimodal associational integration performed by the inferior parietal lobule. The frontal lobes, therefore able to sample activity within all cortical sensory/association regions at all levels of information analysis. FRONTAL-THALAMIC CONTROL OVER NEOCORTICAL ACTIVITY The role of the lateral convexity is not limited to sampling, but also involves regulation of information flow to and within the neocortex. This is accomplished, in part, via projections linking the frontal lobes with the dorsal medial thalamic nucleus--a structure which participates in the transfer of information to the neocortex and which display neuroplasticity (Jones & Pons, 1998). Fibers passing to and from the thalamus and the cortical sensory receiving areas give off collaterals to the reticular thalamic nucleus--which in addition sends fibers which envelop and innervate most of the other thalamic nuclei (Scheibel & Scheibel, 1966; Updyke, 1975). The reticular thalamus maintains reccurent inhibitory interconnections with other thalamic neurons (Huntsman et al., 1999) and acts to synchronize and selectively gate transmission from the thalamus to the neocortex and continually samples thalamic-cortical activity (Skinner & Yingling, 1977; Yingling & Skinner, 1977). The reticular thalamus is controlled by the lateral convexity of the frontal lobes, and the lateral portion of the dorsal medial thalamus with which it maintains dense interconnections (Skinner & Yingling, 1977; Yingling & Skinner, 1977). The convexity and lateral dorsal medial nucleus (LDM) are also richly interconnected and together exert significant steering influences on the reticular thalamus. That is, the lateral frontal convexity appears to exert specific influences on the LDM so as to promote or diminish the flow of information to the cortex and thus modulate specific perceptual and cognitive activities occuring within the neocortex --activity which it is simultaneously sampling. This is in contrast to the orbital region with its connections to the reticular formation and the medial magnocellular segment of the dorsal medial thalamus, and its influences on generalized arousal and limbic activation/inhibition. To recapitulate, the lateral frontal system is able to influence cognitive/perceptual cortical functioning via the sampling of activity occurring throughout the neocortex at all levels of informational analysis, and via its modulating influences on the lateral portion of the dorsal medial and reticular thalamic nuclei. The lateral frontal region is thus able to act at any stage of processing, from initial reception to motor expression so as to facilitate or inhibit further analysis, selectively acting to determine exactly what type of processing occurs throughut the neocortex. Via integration and inhibitory action and through its neocortical and thalamic links the lateral convexity it is able to coordinate interactions between various regions of the neuroaxis so as to organize, mobilize, and direct overall cortical and behavioral activity and to minimize conflicting demands, impulses, distractions and/or the processing of irrelevant information. When damaged, depending on the site (e.g. inferior vs superior convexity) or laterality of the lesion, there can result behavioral disinhibition, flooding of the sensory association areas with irrelevant information, hyperreactively, distractability, memory loss, impulsiveness, and/or apathy, reduced motor-expressive activities (e.g. speech arrest), and sensory neglect (Como et al. 1979; Fuster, 1997; Joseph 1986a, 1999a, Joseph et al. 1981; Passingham, 1993). Similar disturbances can result when the dorsal medial nucleus or the bi-directional pathways linking the thalamus and frontal lobe are severed (Graff-Radford et al.1990; Skinner & Yingling, 1977; Victor et al. 1989). Hence, in summary, the oribtal region exerts modulating influences on subcortical and geralized limbic arousal. By contrast, the lateral convexity of the frontal lobes are "interlocked" with the the sensory receiving areas (Cavada 1984; Fuster 1997; Jones et al. 1978; Jones and Powell 1970; Joseph, 1999a; Pandya and Kuypers 1969) and maintains rich interconnections with the reticular and dorsal medial nucleus of the thalamus (Skinner and Yingling 1977; Yingling and Skinner 1977) which relays sensory impressions to the neocortex. The lateral frontal lobes, therefore are able to sample perceptual input as it is received in the thalamus, and thus prior to and after it has been transferred to the neocortical receiving areas. Through its interconnections with the primary and association areas, the frontal lobes can also censor, inhibit, and thus control the processing of this data, and in this manner can control attention as well as facilitate or inhibit further analysis and thus information processing throughout the neocortex. These frontal capabilities include information storage and retrieval at the neocortical level; i.e. memory (Brewer et al., 1998; Carpenter et al., 1999; Hasegawa et al., 1998; Koechlin et al., 1999; Wagner et al., 1998). In consequence, when the lateral regions are injured, selective attention and memory functioning may become impaired such that individuals may experience sensory-perceptual overload, become distractible, disinhibited, confused, and have difficulty keeping their mind on a certain tasks and/or recalling and acting upon events planned for the future. Similar disturbances can result when the dorsal medial nucleus or the bi-directional pathways linking the thalamus and frontal lobe are severed (Graff-Radford et al.1990; Skinner and Yingling 1977; Victor et al. 1989). However, the nature of these disturbances depends on if the right vs left frontal lobe has been negatively impacted. Whereas left frontal injuries result in reduced functional and expressive activity, right frontal injuries are more likely to be associated with disinhibition, hyperreactively, distractability, impulsiveness, and the flooding of the sensory association areas with irrelevant information (Joseph 1986a, 1988a, 1999a). This is because the right frontal lobe is dominant over the left, and exerts bilateral influences in the regulation of attention and arousal (Cabeza and Nyberg 1997; DeRenzi and Faglioni 1965; Dimond 1976 1979; Heilman and Van Den Abell 1979 1980; Jeeves and Dixon 1970; Joseph 1986a, 1988ab, 1999a; Konishi et al., 1999; Pardo et al. 1991; Tucker 1981). Thus, if the left frontal lobe is damaged, the right, now acting unopposed may exert bilateral inhibitory influences and thus hypo-arousal.
  • Premotor Cortex Area 6,8,9 Responsible for kinetic organization of movement once started, transfer, smooth sequencing. According to Luria, 1973, it is responsible for the conversion of individual motor impulses into consecutive kinetic melodies. A. Oral (buccofacial) Praxis Puff cheeks. Click teeth together three times. Whistle, Protrude tongue Lick lips. Pucker lips. Cough. Blow out a match. Retract lips to show teeth. 10. Sip on a straw. B. Speech/Language Spontaneous speech sample - Note agrammatism and dysprosody. Diadochokinetic rates - Repeat the syllable "puh" as fast as you can: then "tuh": then "kuh"; then put thon together "puh-tuh-kuh". Imitation of monosyllabic and polysyllabic words. Repeat words of increasing length, i.e. thick, thicker, thickening; zip, zipper, zippering; and hope, hopeful, hopefully. Imitation of sentences. C. Intransitive Body movements (Motor Sequencing) Touch fingers with thumb AFAP - reveals paresis, lack of precision, pathological dystonia, ataxia. Separate fingers & bring together AFAP. Alternately clinch and relax fingers of both hands for a long period of time. Bilateral clinching & relaxing fingers AFAP. Finger tapping. Tapping as fast as possible (Speed) Tapping two times with one hand and one time with the other hand and then reversing the pattern (Rhythm). With premotor lesions, movement loses smoothness and each tap is produced as isolated phenomenon; patient begins to make superfluous taps or performs identically with both hands. Snap your fingers. Salute; Fist-Ring Test - can't do them in series; more problems when sequence is reversed. Fist-Edge-Palm Test . Circle Hands In Air . D. Transitive Body Movements Demonstrate playing the piano or typing; piano playing test is forward & then reversed; frontal patients can't reverse; premotor may improve with spoken commands or feedback; frontals may repeat correctly but can't make proper movements. Thread a needle. Tie shoelaces. Cut paper with scissors. Unlock and open a door. Flip a coin. E. Graphics Write words from dictation - can form letters but often disarranges or transposes them. Write sentences from dictation - words may be written correctly but may be in the wrong order. Spontaneous writing. Drawing various shapes,(circle, square, cross) Draw zig-zag line alternating pointed and rectangular elements
  • DETECTION OF FRONTAL LOBE DAMAGE Detection of frontal lobe damage can be difficult, especially if only traditional methods of neurologic testing are carried out. Indeed, this point cannot be overemphasized, since it reflects one of the main differences between traditional neurologic syndromes, which affect only elements of a person's behavior - for example, paralysis following destruction of the contralateral motor cortex -and limbic system disorders generally. In the latter it is the whole of the patient's motoric and psychic life that is influenced, and the behavior disturbance itself reflects the pathologic state. Often, changes can be discerned only with reference to the previous personality and behavior of that patient, and not with regard to standardized and validated behavioral norms based on population studies. A further complication is that these abnormal behaviors may fluctuate from one testing occasion to another. Therefore the standard neurologic examination will often be normal, as may the results of psychological tests such as the Wechsler Adult Intelligence Scale. Special techniques are required to examine frontal lobe function, and care finding out how the patient now behaves and how this compares with his premorbid performance. Orbitofrontal lesions may be associated with anosmia, and the more the lesions extend posteriorly, the more neurologic signs such as aphasia (with dominant lesions), paralysis, grasp reflexes, and oculomotor abnormalities become apparent. Of the various tasks that can be used clinically to detect frontal pathologic conditions, those given in Table 4 are of value. However, not all patients with frontal damage show abnormalities on testing, and not all tests are found to be abnormal in frontal lobe pathologic states exclusively. Table 4. Some Useful Tests at Frontal Lobe Function Word fluency Abstract thinking (if I have 18 books and two bookshelves, and I want twice as many books on one shelf as the other. how many books on each shelf?) Proverb and metaphor interpretation Wisconsin Card Sorting Test Other sorting tasks Block design Maze lest Hand position test (three-step hand sequence) Copying tasks (multiple loops) Rhythm tapping tasks Cognitive tasks include the word fluency test, in which a patient is asked to generate, in 1 minute, as many words as possible beginning with a given letter. (The normal is around 15.) Proverb or metaphor interpretation can be remarkably concrete. Problem-solving, for example carry-over additions and subtractions, can be tested by a simple question (see Table 4). Patients with frontal lobe abnormalities often find serial sevens difficult to perform. Laboratory-based tests of abstract reasoning include the Wisconsin Card Sort Test (WCST) and other object-sorting tasks. The subject must arrange a variety of objects into groups depending on one common abstract property, for example color. In the WCST, the patient is given a pack of cards with symbols on them that differ in form, color, and number. Four stimulus cards are available, and the patient has to place each response card in front of one of the four stimulus cards. The tester tells the patient if he is right or wrong, and the patient has to use that information to place the next card in front of the next stimulus card. The sorting is done arbitrarily into color, form, or number, and the patient's task is to shift the set from one type of stimulus response to another based on the information provided. Frontal patients cannot overcome previously established responses, and show a high frequency of preseverative errors. These deficits are more likely with lateral lesions of the dominant hemisphere. Patients with frontal lobe lesions also do badly on maze learning tasks, the Stroop test, and block design; they show perseveration of motor tasks and difficulty carrying out sequences of motor actions. Skilled movements are no longer performed smoothly, and previously automated actions such as writing or playing a musical instrument are often impaired. Performance on tests such as following a succession of hand positions (with the hand first placed flat, then on one side, and then as a fist, on a flat surface) or tapping a complex rhythm (for example two loud and three soft beats) is impaired. Following nondominant hemisphere lesions, singing is poor, as is recognition of melody and emotional tone, the patient being aprosodic. Perseveration (especially prominent with deeper lesions in which the modulating function of the premotor cortex on the motor structures of the basal ganglia is lost (9)) may be tested by asking the patient to draw, for example, a circle or to copy a complex diagram with recurring shapes in it that alternate one with another. The patient may continue to draw circle after circle, not stopping after one revolution, or miss the pattern of recurring shapes (Fig. 2). Imitation and utilization behavior can also be tested for. In many of these tests there is a clear discrepancy between the patient's knowing what to do and being able to verbalize the instructions, and his failure to undertake the motor tasks. In everyday life this can be extremely deceptive and lead the unwary observer to consider the patient to be either unhelpful and obstructive or (for example, in a medicolegal setting) to be a malingerer. Some of these tasks, for example the word-fluency task, or inability to make melodic patterns, are more likely to be related to lateralized dysfunction, and the inhibition of motoric tasks relates to the dorsolateral syndrome.
  • NEUROANATOMIC BASIS OF FRONTAL LOBE SYNDROMES Several authors have put forward explanations for frontal lobe syndromes. (6,9) The posterolateral areas of the frontal cortex are most closely linked to motor structures of the anterior part of the brain, thus leading to the motor inertias and the perseverations seen with lesions here. They are more pronounced after dominant hemisphere lesions, when the speech-related disorders become manifest. More posterior lesions appear to link with difficulties in organizing movement; anterior lesions result in difficulties in motor planning and a dissociation between behavior and language. Elementary motor perseverations probably require lesions that are deep enough to involve the basal ganglia. Disturbances of attention are related to the brainstem-thalamic-frontal system, and the basal (orbital) syndromes are due to disruption of frontal-limbic links. Loss of inhibitory function over the parietal lobes, with release of their activity, increases the subject's dependence on external visual and tactile information, leading to echo phenomena and the environmental dependency syndrome. Teuber (31) suggested that the frontal lobes "anticipate" sensory stimuli that result from behavior, thus preparing the brain for events about to occur. The expected results are compared with actual experience, and thus smooth regulation of activity results. More recently, Fuster (5) has proposed that the prefrontal cortex plays a role in the temporal structuring of behavior, synthesizing cognitive and motor acts into purposeful sequences. Stuss and Benson (6) put forward a hierarchical concept for the regulation of behavior by the frontal lobes. They referred to fixed functional systems, including a number of recognized neural activities, such as memory, language, emotion, and attention. which are modulated by "posterior" areas of the brain in contrast to the frontal cortex. Two anterior counterparts are proposed, namely, the ability of the frontal cortex to sequence, change set, and integrate information, and to modulate drive, motivation, and will (the former are most strongly dependent on intact lateral, dorsal and orbital frontal convexity regions; the latter are related more to medial frontal structures). A further independent level is that of executive function of the human frontal lobes (anticipation, goal selection, preplanning, monitoring), which is superordinate to drive and sequencing, but may be subordinate to the role of the prefrontal cortex in self-awareness. SUMMARY In this review, some basic aspects of frontal lobe functioning have been discussed and methods of testing for frontal lobe abnormalities outlined. It has been emphasized that the frontal lobes are affected in a number of diseases, which cover a broad spectrum of neuropsychiatric problems. Furthermore, it is suggested that the frontal lobes are involved in syndromes not traditionally thought to be related to frontal lobe dysfunction, for example, schizophrenia, and rarer presentations such as misidentification syndromes, Frontal lobe dysfunction often goes unrecognized, especially in patients who have normal neurologic testing and apparently intact IQ when routine methods of investigation are employed. Although marked disturbances of behavior following frontal lobe dysfunction have now been described for well over 120 years, these large areas of the human brain, and their links with some of the highest attributes of mankind, have been relatively neglected and are worthy of much further exploration by those interested in neuropsychiatric problems.
  • BEHAVIOR PROBLEMS WITH FRONTAL LOBE INJURY One of the specific behaviour deficits following frontal lobe damage is attention disorder, patients showing distractibility and poor attention. They present with poor memory, sometimes referred to as "forgetting to remember." The thinking of patients with frontal lobe injury tends to be concrete, and they may show perseveration and stereotypy of their responses. The perseveration, with inability to switch from one line of thinking to another, leads to difficulties with arithmetic calculations, such as serial sevens or carryover subtraction. An aphasia is sometimes seen, but this is different from both Wernicke's and Broca's aphasia. Luria (9) referred to it as dynamic aphasia. Patients have well-preserved motor speech and no anomia. Repetition is intact, but they show difficulty in propositionizing, and active speech is severely disturbed. Luria suggested that this was due to a disturbance in the predictive function of speech, that which takes part in structuring sentences. The syndrome is similar to that form of aphasia referred to as transcortical motor aphasia. Benson (10) also discusses the "verbal dysdecorum" of some frontal lobe patients. Their language lacks coherence, their discourse is socially inappropriate and disinhibited, and they may confabulate.
  • Other features of frontal lobe syndromes include reduced activity, particularly a diminution of spontaneous activity, lack of drive, inability to plan ahead, and lack of concern. Sometimes associated with this are bouts of restless, aimless uncoordinated behaviour. Affect may be disturbed. with apathy, emotional blunting, and the patient showing an indifference to the world around him. Clinically, this picture can resemble a major affective disorder with psychomotor retardation, while the indifference bears occasional similarity to the "belle indifference" noted sometimes with hysteria. In contrast, on other occasions, euphoria and disinhibition are described. The euphoria is not that of a manic condition, having an empty quality to it. The disinhibition can lead to marked abnormalities of behavior, sometimes associated with outbursts of irritability and aggression. So-called witzelsucht has been described, in which patients show an inappropriate facetiousness and a tendency to pun. Some authors have distinguished between lesions of the lateral frontal cortex, most closely linked to the motor structures of the brain, which lead to disturbances of movement and action with perseveration and inertia, and lesions of the orbital and medial areas. The latter are interlinked with limbic and reticular systems, damage to which leads to disinhibition and changes of affect. The terms "pseudodepressed" and "pseudopsychopathic" have been used to describe these two syndromes." A third syndrome, the medial frontal syndrome, is also noted, marked by akinesia, associated with mutism, gait disturbances, and incontinence. The features of these differing clinical pictures have been listed by Cummings, (12) as shown in Table I. In reality, clinically, most patients display a mixture of syndromes. In some patients, paroxysmal behavior disorders are recorded. These tend to be short-lived, and may include episodes of confusion and, occasionally, hallucinations. They are thought to reflect transient disturbances of the frontolimbic connections. Following massive frontal lobe lesions, the so-called apathetico-akinetico-abulic syndrome may occur. Patients lie around, passive, unaroused, and unable to complete tasks or obey commands. Further clinical signs associated with frontal lobe damage include sensory inattention in the contralateral sensory field, abnormalities of visual searching, echo phenomena, such as echolalia and echopraxia, confabulation, hyperphagia, and various changes of cognitive function. Lhermitte (13,14) has described utilization behavior and imitation behavior, variants of environmental dependency syndromes. These syndromes are elicited by offering patients objects of everyday use and observing that, without instruction, they will use them appropriately, but often out of context (for example, putting on a second pair of spectacles when one pair is already in place). They will also, without instruction, imitate an examiner's gestures, no matter how ridiculous.
  • EPILEPSY The importance of making an accurate seizure diagnosis in patients with epilepsy has been accelerated in recent years by the use of advanced monitoring techniques such as videotelemetry. The more recent classification schemes of the International League Against Epilepsy recognize a major distinction between partial and generalized seizures (20) and between localization-related and generalized epilepsies. (21) In the latest classification (22) the localization-related epilepsies include frontal lobe epilepsies, in several different patterns. The general characteristics of these are shown in Table 2 and their subcategories in Table 3. Table 2. International Classification of Epilepsies and Epileptic Syndromes 1. Localization-related (focal, local, partial) epilepsies and syndromes. 1.1 Idiopathic (with age-related onset) 1.2 Symptomatic 1.3 Cryptogenic 2. Generalized epilepsies and syndromes 2.1 Idiopathic (with age-related onset--listed in order of age) 2.2 Cryptogenic or symptomatic (in order of age) 2.3 Symptomatic 3. Epilepsies and syndromes undetermined as to whether they are focal or generalized. Table 3. Localization-Related (Focal, Local, Partial) Epilepsies and Syndromes 1.2 Symptomatic Chronic progressive epilepsia partialis continua of childhood (Kojewnikow's syndrome) Syndromes characterized by seizures with specific modes of precipitation Temporal lobe Frontal lobe Supplementary motor seizures Cingulate Anterior frontopolar region Orbitofrontal Dorsolateral Opercular Motor cortex Parietal lobe Occipital lobe   They may be anatomically categorized, for example, into seizures arising from the rolandic area, the supplementary motor area (SMA). from polar areas (Brodmann areas 10, 11, 12, and 47), the dorsolateral area, the opercular area, the orbital region, and the cingulate gyrus. Rolandic seizures are typical jacksonian simple partial attacks, while SMA-derived attacks often lead to adversion with posturing and autonomic changes. Characteristic features of complex partial seizures arising from frontal areas include frequent clustering of brief seizures, with sudden onset and cessation. Often, the accompanying motor behavior may be bizarre; and, since the surface electroencephalogram (EEG) may be normal, these attacks may readily be diagnosed as hysterical pseudoseizures. Anatomo-Electroclinical Aspects of Frontal Lobe Seizures Chaired by: Patric Chauvel, France In the past 10 years, significant progress has been achieved in identification of frontal lobe seizures (FLS) and differential diagnosis from temporal lobe seizures, as reflected in the publications from two symposia dedicated to this topic (Chauvel et al., 1992; Jasper et al., 1995). However, the clinical manifestations of FLS remain far from being as well understood and classified as those characterising temporal lobe seizures (TLS). The difficulties in delineating the features of FLS are due to several factors. The frontal lobe covers a large territory of cerebral cortex (40% of the mass of the hemispheres), it is grossly divided into three main regions (prefrontal, premotor and precentral) each with distinct cortico-subcortical organisations and numerous cortico-cortical connections with the temporal and parietal cortices. A very careful analysis is required to make correlations between ictal signs and symptoms and the anatomo-functional organization of the frontal lobe. In addition, the high speed of seizure propagation to other frontal and extra-frontal areas often limits the possibility of firmly establishing these correlations. Some studies have underlined some general characteristics of FLS, in particular for the so-called partial complex seizures of frontal lobe origin. Up to now, the best spatio-temporal and dynamic description of the seizures have been based on intracranial recordings using videotelemetry. Therefore, the plenary session on "anatomo-electroclinical aspects of frontal lobe seizures" will attempt to provide the audience with data from intracerebral recordings of FLS. The transitions and differences between temporal and frontal seizures will be exemplified, as well as the modern trend to consider the regional subdivisions of frontal lobe as parts of distinct neural systems applied to the study of ictal semiology. Finally, the validity of hypothetical separation of FLS in prefrontal, premotor and precentral seizures according to the clinical features of motor signs will be checked and discussed. Two parallel sessions, a tutorial course, and a video-session will complete the program. A first parallel session will present the current knowledge and recent advances on the FLS semiology in children. Clinical semiology of partial seizures in infancy and childhood is hardly described and often limited to its most overt manifestations. Major difficulties usually arise in topographical diagnosis, especially when the motor signs remain subtle, or when, on the other side, they take the mask of paroxysmal behaviour disturbances, sometimes misleading with psychiatric disorders. This session will bring for discussion the experience of epilepsy surgery and potential correlations with lesion topography. Clinical semiology of autosomal dominant nocturnal frontal lobe epilepsy will be presented in comparison with symptomatic epilepsies. Finally, inter-relations and possible overlap with some generalised epilepsies involving, at least partially, frontal cortex, such as Lennox-Gastaut syndrome and Absence epilepsy, will be debated. In a second parallel session, the most recent advances in localisation of frontal lobe seizures, interictal activities, and etiological processes through imaging techniques will be developed. In these localisation-related epilepsies, there is no unifying (or conflicting) pathological concept like hippocampal atrophy in the temporal lobe. The diagnostic situation is more complex than differentiating between "mesial" and "lateral" structures. The distributed organisation of cortical and subcortical areas participating in seizures, the relatively high amount of pharmacoresistant epilepsies without detectable lesions using standard imaging techniques, impose to extend the panoply of physical tools currently available for cerebral localisation. This session will review the MRI sequences, PET ligands, interictal and ictal SPECT, Magnetic Source Imaging (MSI), and fMRI/EEG co-registration methods newly developed in the field of brain imaging, and question their usefulness for frontal lobe epilepsy diagnosis. A tutorial course will be devoted to the management of presurgical investigations of frontal lobe epilepsies in practice. Special attention will be paid to detailed description of the successive steps completed from the individual clinical symptomatology of the patient under investigation to the pre-planned surgical strategy of corticectomy. The distinct role of the different methods used will be explained and the value of anatomo-electro-clinical correlations discussed. Frontal lobe seizures can generate various and complex clinical patterns. Some of them may appear to be idiosyncratic. Only their reproducibility from one seizure to the other in a given patient, from one patient to the other in a series, has convinced epileptologists of their epileptic character and finally of their possible classification. The goal of the video session will be to confront demonstrative observations from different centers and to provoke discussions from the floor on raw clinical material. Some other symposia in the Congress will address topics related to frontal lobe epilepsies. In particular, a symposium on neuropsychiatric aspects of partial epilepsies will compare interictal disturbances in behaviour and cognition according to their cerebral localisation.
  • SCHIZOPHRENIA That neurologic abnormalities underlie the clinical condition schizophrenia is now secure knowledge (see Hyde and Weinberger in this issue of Seminars). However, the precise pathologic lesions and the localization of the abnormalities continue to arouse interest and controversy. Much recent work has highlighted abnormalities of frontal lobe function in this condition. Several authors have drawn attention to the likeness of some schizophrenic symptoms to frontal lobe disorder, in particular that involving dorsolateral prefrontal cortex. Symptoms included are those of the affective changes, impaired motivation, poor insight. and other "defect symptoms." Evidence for frontal lobe dysfunction in schizophrenic patients has been noted in neuropathologic studies, (23) in EEG studies, (24) in radiologic studies using CT measures, (25) with MRI, (26) and in cerebral blood flow (CBF) studies. (27) The last have been replicated by findings of hypofrontality in several studies using positron emission tomography (PET). (28) These findings emphasize the importance of neurologic and neuropsychologic investigation of patients with schizophrenia, using methods that may uncover underlying frontal lobe disturbances, and the important role that frontal lobe dysfunction may play in the development of schizophrenic symptoms. (23)
  • The Frontal Lobe Dementias The Frontal Lobe Dementias are a relatively uncommon form of progressive dementia. They include Pick's dementia and Frontal Lobe Dementia (FLD)-the major difference between the two dementias is the presence of a particular kind of abnormal brain tissue in Pick's dementia that is not present in FLD. Both dementias, however, solely or primarily affect the frontal lobes. The frontal lobes, the most anterior part of the brain which makes up about 30% of the entire brain surface, are concerned with regulating social and interpersonal behavior, mood, planning, reasoning, problem-solving, expression of language, movement control, and strategies used to remember information. Patients who suffer from either of the Frontal Lobe Dementias may demonstrate impairment in just one or many of these areas. The Frontal Lobe Dementias are progressive diseases and eventually patients will require total care. At present the cause(s) of the two main Frontal Lobe Dementias are unknown, and there is no cure. Symptoms The onset of the frontal dementias is gradual. In the beginning of their illness, the patient with Pick's dementia or FLD has trouble in maintaining normal social and interpersonal functioning. They may violate rules of politeness and may make inappropriate remarks. They may become emotionally aroused very easily. Such problems can be embarrassing to friends or family members. Patients may neglect personal hygiene and grooming. The patient can appear to be consumed by eating or obsessed about putting items in his mouth. Stereotyped and ritualistic type behaviors (hoarding belongings) as well as perseverative behaviors (repeating behaviors over and over again) can predominate. As these problems progress, employers may terminate employment, friends may be less willing to spend time with the patient, and family members may feel an increasing burden in caring for the patient. Cognitive abilities can also be affected early in the frontal lobe dementias. The patient may have problems in making decisions, in reasoning about a problem, in carrying out a series of actions in the correct order, in getting the point of a conversation. Patients may also have difficulty placing events into their proper context. This can lead to a patient doing things that seem odd. For example, a patient may try to answer the phone in a doctor's waiting room while waiting to see the doctor. Although answering a phone when it is ringing is an overlearned and appropriate response, social rules dictate that when in another person's office or house, we usually let them answer their own phone. Another patient may want to take a swim at their vacation home in Maine-but in January! Sometimes the patient may grab objects in his environment inappropriately (for example, taking and eating food off a stranger's plate in a fast-food restaurant). Some patients develop problems in manipulating objects or in gesturing. As the disease progresses, patients may become very distractible and impulsive. Lack of insight into their problems may make frank discussion with the patient difficult. The language abilities of patients with frontal lobe dementia may change dramatically over time. For example, early in the course of their disorder, the patient may reduce their production of speech eventually leading them to use the same phrases repetitively. At later stages of Pick's dementia and FLD, patients may be reduced to repeating what others say and eventually may become mute. Throughout the course of this disorder, patients may become depressed, anxious, delusional, and report bizarre preoccupations with bodily sensations and appearance. Some patients may also become rather apathetic to events occurring around them. All these cognitive problems may progress to the point where the patient will need close supervision when participating in daily activities. One or all of the above symptoms may be present even when the patient's ability to recognize sounds, objects, places and friends, to understand language, and to remember day-to-day events are relatively intact. Because intellect, language, perception, and even many motor skills may remain intact, medical personnel and family or friends often overlook the early mild symptoms of Pick’s dementia and FLD. The patient may appear to be a fully functioning member of society to the casual acquaintance who may then become astonished when exposed to the patient's behavior. Other friends or family members may not have the knowledge or psychological resources to understand the patient's behavior. Sometimes the changes in behavior are confused for a psychiatric disorder. Diagnosis The clinical diagnosis of Pick's dementia or FLD requires that a set of core symptoms, like those just described above, be identified. Pick's dementia and FLD usually have a gradual and subtle onset and slow progression. The average time from the appearance of the first symptom until death ranges across studies but usually averages between 5 to 10 years. Patients with Pick's dementia and FLD make up about 10% of all patients with progressive dementia. Women are affected at slightly greater rates than men. Typically, the frontal lobe dementias begin before the age of 65. In about 25% of all patients with a frontal lobe dementia, there may be a family history of the disorder. Pick's dementia and FLD may be accompanied by muscle weakness and wasting as well as the appearance of involuntary twitching in the later stages of the disease. Numerous tests to exclude other forms of dementia as well as other neurologic and psychiatric disorders must always be done as part of the clinical workup of the patient. In many cases, a Magnetic Resonance Image (MRI) of the brain can reveal atrophy (dramatic thinning) of the cortex in the anterior part of the brain. In other cases, despite dramatic behavioral symptoms, no obvious changes are seen on the MRI. Regional patterns of cerebral blood flow can also serve as an aid in clinically differentiating between the frontal lobe dementias (indicated by diminished brain metabolic activity primarily in the anterior part of the brain) and other dementias such as Alzheimer's disease which predominantly affects posterior brain regions (and has relatively diminished brain metabolic activity in the posterior regions of the brain). In addition, in the frontal lobe dementias, diminished frontal lobe metabolism may occur primarily on one side of the brain in a specific location-particularly in the early stages of the disease. No definitive test to diagnosis Pick's dementia or FLD in living patients is available. The abnormal changes to neurons and other brain cells that characterize frontal lobe dementia can only be identified by examining brain tissue and this procedure is usually done as part of an autopsy. The differential diagnosis between Pick's dementia and FLD, and all other dementias can only be confirmed by microscopic examination of the brain tissue in autopsied brains. One kind of abnormal tissue that indicates the presence of Pick's dementia is called a Pick body. Patients with FLD can be distinguished on the basis of their neuropathology that selectively involve the frontal lobes of the brain - in particular, the most anterior part. Patients with FLD almost always have both frontal and anterior temporal lobe involvement. About half the patients with Pick's dementia have both frontal and anterior temporal lobe involvement, 25% have only frontal lobe involvement, and the remaining 25% have posterior brain involvement only. Occasionally, a brain biopsy is done in the living person. In this procedure, a small amount of brain tissue from the frontal lobes is removed by surgical means and the tissue is examined with a microscope for evidence of the presence of abnormal changes in the tissue. Even if such a procedure can confirm the diagnosis of FLD or Pick’s disease, it cannot aid in the management or treatment of the disease. In addition, there are risks associated with a brain biopsy and you should discuss these with your doctor if you are considering such a procedure. In summary, a diagnosis of probable frontal lobe dementia is based on the patient's medical history, a physical examination, neuroradiological studies, and neuropsychological testing. Neuropsychological testing is an objective way to document the patient's intact and impaired cognitive abilities. Multiple testings can chart the progression of the disorder and the effects of an intervention such a drug. Patients should perform particularly poorly on neuropsychological tests of executive functions such as reasoning, problem-solving, planning, and social behavior. A diagnosis that confirms Pick's dementia or FLD can only be obtained at autopsy although, as noted above, a brain biopsy that shows Pick bodies is strongly suggestive of Pick's dementia. Although the early and accurate diagnosis of frontal lobe dementia is difficult, in many specialized centers, it is possible to get a reliable diagnosis with 80 to 90 percent accuracy (when compared with autopsy findings). Treatment At this time, there is no effective treatment for frontal lobe dementia that can stop the progression of the disorder. Some drugs are useful for easing the symptoms in some patients, thereby making patients more comfortable and management easier for caregivers. For example, medication to improve sleeping patterns, reduce wandering, or ease the anxiety and depression that may develop in some patients is available. These drugs are not specifically designed to reverse the frontal lobe dementias but may be utilized to help manage the Pick's dementia or FLD patient's behavior. Patients with Pick's dementia or FLD should be checked regularly by a neurologist, psychiatrist, or geriatrician as well as a neuropsychologist to monitor the progress of the disease, and to treat any other illnesses and aggravating symptoms that may occur during its course. Other health professionals (e.g., social workers) can also offer guidance and support to the family and friends of the patient. Most often, the spouse or another family member provides the day-to-day care of the Pick's dementia or FLD patient. As the disease progresses and the patient requires more supervision, the job of caregiving can become overwhelming and can affect the caregivers mental and physical health, family life, career, and finances. Caregivers need to seek occasional respite from this enormously taxing responsibility. In addition, as soon as the diagnosis of FLD or Pick’s disease is made, the caregiver and the family need to familiarize themselves with the health care, financial, and insurance options available to them in the years ahead. Given that FLD and Pick’s disease are progressive dementing illnesses, planning ahead by the family will help minimize the stress that they will experience when having to make difficult decisions about the FLD patient’s care, living situation, and financial status. There is currently no specific organization dedicated to assistance and service for families with a member who has frontal lobe dementia. Many patients and their families contact the Alzheimer's Association or the National Organization for Rare Disorders. These private service organizations have local chapters nationwide that provide educational programs and support groups for caregivers and family members. For contact information, see the listings at the end of this fact sheet. Research Scientists at Medical Research Centers and Universities across the country and throughout the world are trying to learn what causes Pick's dementia and FLD and how to manage and prevent them. They have identified abnormal brain cell loss and the structures called Pick bodies which characteristically develop and spread throughout the frontal lobes of the brain reflecting both the disease and its progression. Little is known about the neurochemical changes that accompany the frontal lobe dementias although there is some evidence of a depletion of the brain chemical serotonin. A number of risk factors are under study. Researchers believe that inherited (genetic) factors may be involved in as many as half the patients with FLD whereas the role of genetic factors in Pick's dementia appears much smaller. However, genetic factors alone may not be enough to bring on these disorders; other risk factors may combine with the person's genetic make-up to increase the chance of developing the disease. Genetic markers, or indicators, have not yet been found for families with FLD or Pick's dementia. Unfortunately, no blood or urine test can detect or predict FLD or Pick's dementia. Another possible risk factor, environmental toxins, is also being examined. For example, the detection of trace metals in the brain tissue of FLD and Pick's dementia patients is being studied to see whether such deposits, if present, may influence the disease process or whether they are simply the result of disrupted brain structures. Other research focuses on the possibility that a virus may be involved in FLD or Pick's dementia. Neuropsychological research with patients who have Pick's dementia or FLD is aimed at gaining a better understanding of the functions of the prefrontal cortex. In particular, scientists are investigating the nature of social cognition, planning, reasoning, and story understanding. In their search for treatments for dementia, scientists are just beginning to investigate drugs that might improve social behavior and other thought processes, including drugs that increase levels of brain chemicals. In addition, researchers are looking for ways to strengthen already weakened or damaged brain cells. However, there are no current drug trials specifically aimed at treating or modifying the progression of the frontal lobe dementias. Other research is aimed at helping both patients and caregivers cope with the patients' loss of abilities associated with the frontal lobe dementias and the increased stress this places on the caregivers. For example investigators are examining ways to manage difficult patient behaviors such as wandering, aggression, lack of social restraint, incontinence (loss of bladder control), and agitation. Still other research efforts focus on alternative care programs that provide relief to the caregiver and support for the patient. Some communities are designing and evaluating programs to help patients retain optimal functioning. Paranoia and Memory Loss/Frontal Lobe Dementia By Piero G. Antuono, MD, Professor, Department of Neurology and Pharmacology, Director, Memory Disorders Clinic, Medical College of Wisconsin. Case Presentation Alzheimer's disease is the most common neurological disease of adult life. It afflicts 4 million people in the United States, and it's incidences increase with age. The early symptoms are characterized by an insidious onset and gradual progression of memory loss. Some dementias, however, do not follow this pattern. Vascular dementias have recently been characterized by specific diagnostic criteria. They can be summarized by sudden onset of dementia and step-wise progression with focal neurological findings and positive brain imaging. Lewy body dementia is characterized by early appearance of symptoms in the course of dementia, accompanied by progression and hallucinations. Primary progressive aphasia includes early dissolution of speech in an otherwise cognitively intact individual. They can become globally aphasic in spite of being able to continue to run a household or even work. Eventually 20% per year progress to dementia, which appears similar in the advanced states to Alzheimer's disease. Frontal lobe dementias are characterized by early psychiatric symptoms followed later by cognitive impairments. Frontal lobe syndrome is therefore the presenting symptomatology: apathy, poor social judgment, and bizarre behavior. Histologically, the frontal lobe dementias are proven to be characterized by Pick's cells (Pick's disease). At the present time, these diverse histological types are clinically indistinguishable. When degenerative neurological diseases affect the subcortical structures, it may cause apathy and slowness of thinking which can be mistaken for dementia. Examples of such conditions are Parkinson's disease, olivo-ponto cerebellar atrophy (OPCA), and hydrocephalus. The following cases will illustrate a patient with frontal lobe dementia and OPCA as examples of uncommon dementias. History A 74-year-old white woman was noted to have undergone a drastic personality change over the last year. She was described as becoming much quieter with several instances of paranoia and suspiciousness. The onset of these changes was described as slow with a gradual progression. She was preoccupied with her own safety. She always locked the house, even when her husband went to mow the lawn. She has been known to prop the back door closed with a shovel. When driving in the evening, she would disguise herself as a man, putting her hair up in a black knit cap. The patient's daughter removed a handgun from the home. Within one week the patient purchased another one. She looks for the gun every morning to make sure she knows where it is. At the present time the patient has hidden the gun and the bullets. She has accused her husband of having an affair. The patient, who was quite neat in the past, has become disheveled, not paying attention to her dressing and hygiene. Her ability to cook and clean the house has significantly deteriorated. In particular, she has developed hiding and hoarding behaviors. She was resistant to throwing anything away, including spoiled food. She tended to "over shop" and pack the freezer and refrigerator with food. Recently, she had become obsessed with winning the sweepstakes, and has ordered many books in order to enhance her chance of winning. The husband denied his wife has significant memory problems. There is no noted difficulty with memory loss or ability to recognize people or objects. She has shown no difficulty with driving a car, getting lost, or using household appliances and the telephone. The patient has a masters degree in education and has maintained her interests and hobbies, which include learning a foreign language. Examination The neurological examination was normal. There was no evidence of dyspraxia or dysnomia during the evaluation. Visual spatial skills appeared to be intact. The Mini Mental State Examination score was 29/30. There was no depression and mood and affect were congruent. Some difficulty was present with abstract thinking. Neuropsychological testing showed intact remote memory, fluent speech, and non-labile affect. The patient was oriented to time, place, and person. The performance on tests of memory was in the average range. Her constructional and organizational skills were normal. The patient's response to a self-reported depression inventory were also within normal limits. However, on the test of verbal abstraction and reasoning, the patient performed in the low average range. Her ability to generate words was poor, also in the low average range. There was evidence of perseveration. Similarly, there was impairment on tasks which required shifting strategies. Concept formation and mental flexibility was moderately impaired. In summary, the neuropsychological testing was consistent with normal range for attention, visual spatial processing, and naming. In contrast, the patient had difficulty with executive functioning tasks such as verbal fluency, verbal abstraction, concept formation, and mental flexibility suggesting a predominantly largely frontal lobe dysfunction. MRI showed a soft tissue lesion in the fourth ventricle (Fig. 1). This was consistent with a probable subependymoma which was thought to be an incidental finding. There was evidence of frontal lobe atrophy (Fig. 2). Figure 1. MRI T-2 study showing a fourth ventricle lesion likely an ependymoma. Figure 2. MRI T-1 study showing predominantly frontal lobe atrophy. The findings are suggestive of a degenerative disease of the frontal lobes. The presence of impaired judgment and executive skills with normal visual spatial and mnemonic function seem to suggest this condition. These "frontal lobe" dementias histologically have been proven to be consistent with Pick's disease, subcortical gliosis, or simple neuronal loss. The history of normal cognitive performance in the face of poor judgment, poor executive function, and the imaging consistent with frontal lobe involvement are the basis of this diagnosis. In the later stages as the dementia progresses involving posterior cerebral functions, it resembles Alzheimer's disease. Management is more challenging in the early stages than in Alzheimer's disease due to poor judgment and safety risks these patients represent. Because of this, they tend to be institutionalized earlier than patients with Alzheimer's disease. Back to Picks directory Back To Other Dementias Directory FRONTAL LOBE DEMENTIA AND PICK'S DISEASE Like Alzheimer's disease, Pick's disease and frontal lobe dementias cause a progressive and irreversible decline in a person's abilities over a number of years. Frontal lobe dementia and Pick's disease are the cause of less than 10% of all dementias and may usually be distinguished from Alzheimer's disease early in the course of the illness. Arnold Pick first described Pick's disease in a 71 year old man in 1892. Pick's disease affects the temporal lobes of the brain in 25% , frontal lobes in 25% and both frontal and temporal lobes in 50% of cases. Frontal lobe dementia affects the frontal lobes initially. Damage to the frontal lobes leads to alterations in personality and behaviour, changes in the way a person feels and expresses emotion, and loss of judgement. The following information about Pick's disease is also appropriate for other frontal lobe dementias. THE MORE COMMON SYMPTOMS INCLUDE: Personality and Behavioural Problems The first symptoms of Pick's disease are typically psychological and behavioural problems. Initially, the diagnosis may be suspected to be a mental illness. People may show symptoms of a change in their character and in their social behaviour. They may have a diminished drive and often their expression is vacant. A person with Pick's disease may show insensitivity, which is especially noticeable in a person who previously showed consideration to others. There may be a lack of restraint and the person may be caught up in the criminal justice system because of stealing or behaviour which lands him/her in trouble. Another sign of Pick's disease is that the person often becomes quite obsessional during the early stages, insisting that everything is absolutely neat and in order, or repeatedly washing his hands or observing little rituals each time a certain task is carried out. There may be sexual misadventures, social graces may deteriorate, the person may talk to strangers, make inappropriate comments in public and indulge in practical jokes. Unfortunately, people with Pick's disease often suffer from significant absence of insight into the effects of their behaviour. Language Problems Language problems also occur early in the disease: limited speech output, lack of speech spontaneity, stereotyping of phrases (ie., use of pat phrases repeatedly and excessively), perseveration (a meaningless persistence of verbal activity), a decreased vocabulary, a considerable amount of repetition, especially of brief words and phrases. Often there is jargon and instead of being able to find the word to describe an object, the person with this disease will give a description of it instead (ie., a "watch" referred to as "something you tell the time with"). This means that the person may not be able to name objects early in the disease. Eventually the person becomes mute for periods and then completely mute by the end of the disease. Kluver Bucy Syndrome This refers to a group of problems which are relatively common in Pick's disease. These are hypersexuality, gluttony, and an obsession to touch and seize any objects in the person's field of vision. Overeating may lead to considerable weight gain. WHO CAN GET THE DISEASE? Anybody can get the disease, although there may be geographical differences in the incidence of Pick's disease. Some studies suggest the disease to be more common in women while others suggest a greater risk in men. The most severe cases of Pick's disease occur before the age of 60 years. The highest incidence is between 50 and 60, but people may develop the disease earlier or up to 80 years. WHAT IS THE CAUSE? As with Alzheimer's disease, in most cases, the cause cannot yet be determined. However, there are strong genetic components in certain families. When there is a genetic element, it is autosomal dominant, (on average, half of the children of an affected parent will develop the disease, but half will not) but is clearly modified by a number of environmental factors as yet to be discovered. The genetic component has been variously described as affecting 20 to 50% of people with Pick's disease. DIAGNOSIS: Although Pick's disease can only be conclusively diagnosed after a person's death by a post mortem examination of the brain, there are several techniques, such as brain scans and EEGs, which can be used during the person's lifetime to give a probable diagnosis. These techniques can help in determining whether the dementia is likely to be Pick's disease or a closely related disorder, for example, Alzheimer's disease. PROGNOSIS and TREATMENT: As yet, there is no cure for Pick's disease, neither can the progression be slowed down with any drug treatment. Probably because Pick's disease is much less common than Alzheimer's disease, there is less research into Pick's, and there are currently no drug trials taking place in relation to treating Pick's disease. The course of Pick's disease is an inevitable progressive deterioration. From the onset of the disease, life expectancy is 2-15 years, with an average of 6-12 years. Death is usually caused by infection. Some of the symptoms of the disease can be treated effectively. For example, certain medications can reduce some of the behavioural problems. Also knowing more about the disease and why the person is behaving as they are can in itself be an effective means of helping people to cope with the disease. (The Alzheimer's Association NSW has an extensive dementia library, education and counselling services). DIFFERENCES BETWEEN PICK'S DISEASE AND ALZHEIMER'S DISEASE: The main difference between Pick's disease and Alzheimer's disease is that the damage occurs in different areas of the brain, at least in the early stages. In most cases of Pick's disease, the frontal and temporal lobes of the brain are the areas affected and with Alzheimer's disease, the temporal and parietal lobes are affected. Mendez and co-workers (1993) found, even in the absence of temporal or frontal lobe atrophy on CT brain scans, that Pick's disease can be distinguished from Alzheimer's disease if three of the following five characteristics are present early in the disease: presenile onset (under 65 years old); initial personality change; hyperorality (loss of normal controls, ie., excessive eating, indiscriminate putting things in one's mouth); disinhibition; roaming behaviour. Compared with Alzheimer's disease, impairment of intellect and memory occur later. As well, epilepsy is uncommon, delusions and hallucinations are rare, and apraxia (inability to perform, command, or imitate a familiar action) and agnosia (inability to recognise objects) are less common. Gait and muscle tone are less affected. In the late stages, Parkinsonism symptoms, immobility, incontinence and mutism occur. In the terminal stage, the different dementias are clinically undistinguishable. CARERS: Being a family carer of a person with dementia, regardless of whether it's Alzheimer's disease, Pick's disease or another type, can be physically and emotionally exhausting. However, Pick's disease can often be even harder on families because: of the personality changes and behavioural quirks which are very distressing; often there is a delay in diagnosis of the disease; it receives less publicity than Alzheimer's disease and therefore, is even less understood by the public, friends, etc. often, persons affected with Pick's disease are younger; language problems develop earlier. Families of people with Pick's disease and other frontal lobe dementias need support in their caring role. The Alzheimer's Association NSW offers a variety of support services which can be accessed by ringing their HelpLine on 1800 639 331. The majority of this HelpNote was written by Dr Keith Fleming, Department of Geriatric Medicine, ACT. It has been edited by Professor Henry Brodaty, Department of Psychogeriatrics, Prince Henry Hospital and Honorary Medical Adviser to the Alzheimer's Association NSW. REFERENCES: Berrios G.E.; Freeman H.L. (1991) Alzheimer and the Dementias: Eponymists in Medicine. Royal Society of Medicine Series. - London. Brun A. (1987) Frontal Lobe Degeneration of Non-Alzheimer Type 1 Neuropathology. Arch. Gerontol. Geriatr., 6, p. 193-208. Mendez M.F., et al (1993) Pick's Disease Versus Alzheimer's Disease: A Comparison of Clinical Characteristics. Neurology, 43(2), p. 289-292. Brown, Jeremy; Rossor, Martin (1996) Pick's Disease and Frontal Lobe Dementia. - Alzheimer's Disease Society UK DEMENTIA The dementias are assuming increasing importance in psychiatric practice, and progress has been made with regard to classifying them and to discovering their underlying neuropathologic and neurochemical basis. While many forms of dementia involve frontal lobe changes, it is now clear that several types of dementia more selectively affect frontal lobe function, particularly early in the disease. The paradigm of frontal lobe dementia is that described by Pick in 1892, which was associated with circumscribed atrophy of both the frontal and temporal lobes. This form of dementia is much less common than Alzheimer's disease. It is more frequent in females. It may be inherited through a single autosomal dominant gene, although most cases are sporadic. There are distinguishing features that reflect the underlying pathologic changes of Pick's disease and separate it from Alzheimer's disease. In particular, abnormalities of behavior, emotional changes, and aphasia are frequent presenting features. Some authors have noted elements of the Kluver-Bucy syndrome at one stage or another in the disease. (29) Interpersonal relationships deteriorate, insight is lost early, and the jocularity of frontal lobe damage may even suggest a manic picture. The aphasia is reflected in word-finding difficulties, empty, flat, nonfluent speech, and aphasia. With progression, the cognitive changes become apparent: these include memory disturbance but also impairment on frontal lobe tasks (see later). Ultimately, extrapyramidal signs, incontinence, and widespread cognitive decline are seen. The EEG tends to remain normal in this disease, although CT or MRI will provide confirmatory evidence of lobar atrophy. The PET picture confirms diminished metabolism in frontal and temporal areas. Pathologically, the brunt of the changes is borne by these areas of the brain and mainly consists of neuron loss with gliosis. The characteristic change is the "balloon cell" which contains disordered neurofilaments and neurotubules, and Pick bodies, which are silver-staining and are also composed of neurofilaments and tubules. Recently, Neary and colleagues (30) have drawn attention to a group of patients with non-Alzheimer's dementia who typically present with changes of personality and social conduct and with atypical Pick's changes in the brain. They note that this form of dementia may be more common than previously thought. Another form of dementia that primarily affects frontal lobe function is that of normal pressure hydrocephalus. This may be related to several underlying causes, including cerebral trauma, previous meningitis, neoplasia, or subarachnoid hemorrhage, or it may occur idiopathically. Essentially, there is a communicating hydrocephalus with failure of absorption of cerebrospinal fluid (CSF) via the sagittal sinus through blockage, the CSF being unable to reach the convexity of the brain or be absorbed through the arachnoid villi. The characteristic clinical features of normal pressure hydrocephalus include gait disturbance and incontinence, with normal CSF pressure. The dementia is of recent onset and has characterist
  • Frontal lobe

    1. 1. Frontal Lobe
    2. 2. Frontal lobe development <ul><li>33% of Brain area </li></ul><ul><li>Most recently evolved </li></ul><ul><li>Well developed only in primates </li></ul><ul><li>Human species is due to frontal lobe </li></ul><ul><li>Last to develop in ontogeny from age 1-> 6years </li></ul>
    3. 3. Frontal lobe <ul><li>Lateral surface </li></ul><ul><ul><li>Posterior - Central sulcus </li></ul></ul><ul><ul><li>Inferio-Posterior – sylvian fissure. </li></ul></ul><ul><li>Medial sufface </li></ul><ul><li>Orbital surface </li></ul>
    4. 4. Lateral surface <ul><li>Precentral sulcus – parallel to central sulcus between them precentral gyrus </li></ul><ul><li>Sup and inf frontal sulci divide sup, middle and inf frontal gyri </li></ul>
    5. 5. Medial surface <ul><li>Between cingulate sulcus and superior medial margin of hemisphere </li></ul><ul><li>Posterior part vertical sulcus – paracentral lobule </li></ul>
    6. 6. Orbital surface <ul><li>D ivided into four orbital gyri by a well-marked H-shaped orbital sulcus. </li></ul><ul><li>T he medial, anterior, lateral, and posterior orbital gyri. </li></ul><ul><li>The medial orbital gyrus presents a well-marked antero-posterior sulcus, </li></ul><ul><li>the olfactory sulcus, for the olfactory tract; </li></ul><ul><li>the portion medial to this is named the straight gyrus, and is continuous with the superior frontal gyrus on the medial surface. </li></ul>
    7. 7. Prefrontal cortex <ul><li>~ 1/3 of cortical surface </li></ul><ul><li>Most recently evolved </li></ul><ul><li>Well developed only in primates </li></ul><ul><ul><li>the advent of the human species: &quot;age of the frontal lobe&quot; </li></ul></ul><ul><li>develops late in ontogeny </li></ul><ul><ul><li>differentiation through age 1 </li></ul></ul><ul><ul><li>maturation through age 6 </li></ul></ul>
    8. 8. Connectivity of Prefrontal regions <ul><li>input from association cortex (occipital, parietal, temporal & olfactory areas) </li></ul><ul><li>convergence of higher-order input from all modalities. </li></ul><ul><li>reciprocal connections: prefrontal processing modulates perceptual processing. </li></ul><ul><li>LIMBIC connections (memory/emotion) </li></ul><ul><li>Input to premotor areas - controls/programs behavior. </li></ul>
    9. 9. Premotor & Motor Areas <ul><li>Premotor areas (6) - input from prefrontal regions and parietal association areas (5,7). </li></ul><ul><li>Area 4: primary motor cortex </li></ul><ul><ul><li>input from premotor area (6) and area 44 </li></ul></ul><ul><ul><li>sends output to spinal cord, and other motor structures (basal ganglia) </li></ul></ul><ul><li>Frontal network controls voluntary, planned actions. </li></ul>
    10. 10. Paradigm shift <ul><li>Broca </li></ul><ul><ul><li>Loss of an area of brain -> loss of function of that area ( Neurologic dificit) </li></ul></ul><ul><li>Jackson </li></ul><ul><ul><li>Loss of an area of brian -> emergence of new function suppressed by that part ( Realese phenomenon) </li></ul></ul>
    11. 11. Phinease Gage (1848) <ul><ul><li>On 13 th Sept 1848 a railroad worker </li></ul></ul><ul><ul><li>A hard working, diligent, reliable, responsible, intelligent, good humored, polite god fearing, family oriented foreman </li></ul></ul><ul><ul><li>Following an explosion iron bar drove into frontal lobe </li></ul></ul><ul><ul><li>1. He becomes unreliable and fails to come to work and when present he is &quot;lazy.&quot; </li></ul></ul><ul><ul><li>2. He has no interest in going to church, constantly drinks alcohol, gambles, and &quot;whores about.&quot; </li></ul></ul><ul><ul><li>3. He is accused of sexually molesting young children. </li></ul></ul><ul><ul><li>4. He ignores his wife and children and falfls to meet his financial and family obligations. </li></ul></ul><ul><ul><li>5. He has lost his sense of humour. </li></ul></ul><ul><ul><li>6. He curses constantly and does so in inappropriate circumstances. </li></ul></ul><ul><ul><li>7. Died of status epilepticus in 1861 </li></ul></ul>
    12. 12. History <ul><li>Dandy’s (1936) </li></ul><ul><ul><li>following bilateral frontal lobotomy during removal of meningioma </li></ul></ul><ul><li>Feuchtwanger (1923) </li></ul><ul><ul><li>200 case of frontal lobe injury </li></ul></ul><ul><ul><li>Lack of initiative </li></ul></ul><ul><ul><li>Vacillation </li></ul></ul><ul><ul><li>Euphoria </li></ul></ul><ul><ul><li>Inattentiveness </li></ul></ul><ul><ul><li>Normal intellect and memory </li></ul></ul><ul><li>Jacobson (1935) </li></ul><ul><ul><li>Premotor lobotomy in primates -> </li></ul></ul><ul><ul><li>Social indifference </li></ul></ul><ul><ul><li>Tameness </li></ul></ul><ul><ul><li>Placidity </li></ul></ul><ul><ul><li>Forgetfulness </li></ul></ul><ul><ul><li>Difficulty in problem solving  </li></ul></ul><ul><li>Egas Moniz </li></ul><ul><ul><li>Prefrontal lobotomies in psychotics </li></ul></ul>
    13. 13. Frontal lobe function Spontaneity Mood and affect Abstract thinking Initiation Impulse control Judgment Eye movements Social and sexual Problem solving Language Expression Attention Personality Memory Voluntary movements Arousal Behavior Cognitive Motor
    14. 14. Beyond Motor Planning <ul><li>Frontal lobe has evolved from being the main motor planner/organizer to a higher level behavioral/strategic planner/organizer. </li></ul><ul><li>Mental model, considering options, selecting behaviors based on context, feedback, stored knowledge </li></ul><ul><li>Making predictions about what will work. </li></ul>
    15. 15. Impaired divergent thinking <ul><li>Decreased consideration of alternative strategies/behaviors; reduced flexibility </li></ul><ul><li>Decreased spontaneity, initiative, may appear lazy, unmotivated </li></ul><ul><li>Knowledge/intelligence may seem intact (e.g. IQ) but its not used to generate strategies or solve problems efficiently </li></ul>
    16. 16. Decreased Inhibition <ul><li>Problems inhibiting incorrect/ineffective responses & switching to a new strategy </li></ul><ul><li>Perseverates; not responsive to feedback or changes in environment </li></ul><ul><li>Violates rules, expectancies; takes risks </li></ul><ul><li>Not adaptable </li></ul><ul><li>Decreased social inhibitons as well </li></ul>
    17. 17. Supplementary Motor area <ul><li>Rostral to motor cortex on the medial surface </li></ul><ul><li>Caudal part of proper SMA F3 projects to spinal cord and motor cortex. </li></ul><ul><li>Rostral part of pre-SMA F6 – receive projections from the prefrontal and cingulate motor area. </li></ul><ul><li>Supplementary eye field </li></ul>
    18. 18. Impaired association learning <ul><li>Reduced response to consequences </li></ul><ul><li>Impaired on delayed response tasks </li></ul><ul><li>Impaired responsiveness to social & contextual cues </li></ul>
    19. 19. Impaired temporal learning <ul><li>Impaired memory for order, recency </li></ul><ul><li>Could affect problem-solving, planning and impair systematic, organized behaviors </li></ul>
    20. 20. Personality and emotional changes <ul><li>Apathetic, indifferent, loss of initiative, lack of emotion or somewhat depressed, little verbal output. Most common after left frontal damage; called &quot;pseudodepression&quot; </li></ul><ul><li>Lack of tact & restraint, immature, coarse,lack of social graces, inappropriate sexual behavior, increased motor activity. More common after right frontal damage; called &quot;pseudopsychopathic&quot; </li></ul>
    21. 21. Mediate voluntary control of behavior... <ul><li>ANTI-saccade task </li></ul><ul><li>saccade AWAY from an eccentric target </li></ul><ul><li>patients w/ prefrontal damage including FEF (Area 8): </li></ul><ul><ul><li>reflexive saccades to the target. </li></ul></ul><ul><ul><li>Cannot correct error and make anti-saccades </li></ul></ul><ul><ul><li>e.g., left lesion patients impaired on right anti-saccades </li></ul></ul>+
    22. 22. Poor performance on Anti-saccade task <ul><li>Why more reflexive saccades ? </li></ul><ul><ul><li>Superior colliculus- control rapids, stimulus-driven eye movements. </li></ul></ul><ul><ul><li>Disinhibited by frontal lobe damage, &quot;releasing&quot; reflexive glances </li></ul></ul><ul><li>Why were Anti saccades impaired? </li></ul><ul><ul><li>Difficulty forming representation of goal to control voluntary behavior. </li></ul></ul>
    23. 23. Model task to study frontal lobe function: <ul><li>Delayed Response Task </li></ul><ul><li>Correct response requires keeping baited well in mind . </li></ul><ul><li>Monkeys and humans w/lesions of LPFC fail these tasks. </li></ul><ul><li>Infants younger than 12 months also fail versions of these tasks. </li></ul>
    24. 24. Delayed Saccade Task (Goldman-Rakic) <ul><li>Single unit recordings from principal sulcus (Brodmann's 46). </li></ul><ul><li>TASK: </li></ul><ul><li>Cue one of 8 locations </li></ul><ul><li>3 sec. delay </li></ul><ul><li>fixation removed signaling GO </li></ul><ul><li>Saccades to remembered location </li></ul>
    25. 25. Cognitive Role of area 46 <ul><li>Delay activity -- location specific </li></ul><ul><li>Delay activity reduced when monkeys made errors. </li></ul><ul><li>Lesions of 46 impair performance on this task. </li></ul><ul><li>Interpretation: </li></ul><ul><li>Neural activity corresponds to mental representation of a GOAL </li></ul><ul><li>The goal is maintained &quot;on-line&quot; available for use. </li></ul><ul><li>This is working memory. </li></ul>
    26. 26. Without goal representation... <ul><li>Behavior is determined by </li></ul><ul><li>reflex </li></ul><ul><li>habit </li></ul><ul><li>past-reward (perseveration) </li></ul><ul><li>immediate stimulus conditions </li></ul><ul><li>Rather than by intentions that integrate the relevant current spatial and temporal context. </li></ul>
    27. 27. Memory defect <ul><li>Part of more general disturbance in thinking </li></ul><ul><li>Can recall the details of problem, error in trying to solve </li></ul><ul><li>Could not put them to use in the correction of further performance. </li></ul><ul><li>Cannot categorizes series of item in group for recall </li></ul>
    28. 28. Frontal lobe and arousal <ul><li>Right frontal lobe exerts bilateral influences on arousal </li></ul><ul><li>The right frontal lobe is also larger than the left suggesting a greater degree of interconnections with other brain tissue, and it appears to exert bilateral inhibitory influences on attention and arousal </li></ul><ul><li>However, because the right frontal lobe appears to exert bilateral inhibitory influences, whereas the influences of the left are unilateral and excitatory, when the left frontal region is damaged, the right may act unopposed and there may be excessive left cerebral inhibition or reduced activity </li></ul>
    29. 29. Problem solving <ul><li>Unable to think all the option and select appropriate </li></ul><ul><li>Fails to conceptualize all the demands of the situation but thinks “concretely” – think and react directly to the stimulus </li></ul>
    30. 30. Problem solving - Luria <ul><li>Normal </li></ul><ul><ul><li>The specification of problem and the condition in which it has arisen </li></ul></ul><ul><ul><li>A plan of action or strategy for the solution of the problem is formulated </li></ul></ul><ul><ul><li>Execution, including implementation and control of the plan </li></ul></ul><ul><ul><li>Checking of the results against the original plan </li></ul></ul><ul><li>Frontal lobe lesion </li></ul><ul><ul><li>Erroneous analysis of the condition of the problem </li></ul></ul><ul><ul><li>The plan of action that is selected quickly loses its regulation influence on behavior as a whole and is replaced by a perseveration of one particular link of the motor act or by the influence of some connection established during the patient's past experience. </li></ul></ul>
    31. 31. Personality and behavior <ul><li>Lack of initiative and spontaneity </li></ul><ul><li>Placidity: worry, anxiety, self concern, hypochondriasis, and pain reduces </li></ul><ul><li>Psychomotor retardation: number of movements, spoken words and thought per unit of time diminish. Mild form abulia and severe akinetic mutism. </li></ul><ul><li>Organic driveness: brief but intense meaningless activity. </li></ul><ul><li>Loss of ego strength: Witzelsucht or moria : socially uninhibited and lack aunawerness of their abnormal behavior. </li></ul><ul><li>Loss of regards to social conventions , only interested in personal gratification. </li></ul>
    32. 32. Disinhibited sexuality <ul><li>It is not unusual for a hypersexual, disinhibited frontal lobe injured individual to employ force. </li></ul><ul><li>spirited physical self-defense is probably the best strategy of the woman. Her husband may have regressed to the cave-man level, and she owes it to him to be responsive at the cave-women level. It may not be agreeable at first, but she will soon find it exhilarating if unconventional.&quot; </li></ul><ul><li>Seizure activity arising from the deep frontal regions have also been associated with increased sexual behavior, including sexual automatisms, exhibitionism, gential manipulation, and masturbation </li></ul>
    33. 33. Unilateral Frontal lobe Syndrome <ul><ul><li>1. Contralateral hemiplegia </li></ul></ul><ul><ul><li>2. Conjugate deviation of eye to side of lesion </li></ul></ul><ul><ul><li>3. Personality change (Psudopsychotic) </li></ul></ul><ul><ul><ul><li>a. Mood elevation, talkativeness </li></ul></ul></ul><ul><ul><ul><li>b. Tendency to joke, lack of tact, silly and childish behavior </li></ul></ul></ul><ul><ul><li>4.  Difficulty in adaptation </li></ul></ul><ul><ul><li>5.  Loss of initiative </li></ul></ul><ul><ul><li>6.  Loss of kinetic melody </li></ul></ul><ul><ul><li>7.  Unable to solve problem </li></ul></ul><ul><ul><li>8.  Anosmia and blindness </li></ul></ul>
    34. 34. Dominant Frontal lobe <ul><li>1. Loss of motor speech </li></ul><ul><li>2. Unable to write </li></ul><ul><li>3. Sympathetic apraxia </li></ul><ul><li>4. Dysphoria </li></ul><ul><li>Deficits in tests of categorization and flexibility. </li></ul><ul><li>Problems with body schema (autopagnosia) due to problems of scanning, perceptual shifting and postural mechanisms. </li></ul><ul><li>Marked inactivity affects general intellectual processes and behavior. </li></ul><ul><li>Cannot change verbal instructions into acts, especially when the instructions are complex or symbolic. </li></ul><ul><li>Decreased spontaneity of speech; may result in complete loss of voluntary speech. </li></ul><ul><li>Memory deficits for verbal material; however, deficits may be due to defective registration. </li></ul>
    35. 35. Right hemis. prefrontal lesions <ul><li>Loss of emotional speech expression </li></ul><ul><li>Euphoria </li></ul><ul><li>Constructional apraxia, associated with motor rather than perceptual difficulties; deficits may occur as a function of impaired complex (3-D) spatial analysis. </li></ul><ul><li>Large lesions may exist without obvious symptoms; serious speech disorders usually not seen in right hemisphere lesions. </li></ul><ul><li>Difficulty with drawing tasks, though this is associated more with right hemisphere lesions in general. </li></ul><ul><li>Impaired visual-spatial integration, maze learning, non-verbal visual memory </li></ul>
    36. 36. Bilateral Frontal lobe lesion <ul><li>1. Pseudodepressed - Apathy, Abulia, akinetic mutism, </li></ul><ul><li>2. Impulsiveness and irritability </li></ul><ul><li>3.  Inability to sustain attention </li></ul><ul><li>4.  Decomposition of gait </li></ul><ul><li>5.  Sphincter disturbance </li></ul><ul><li>6. Active learning, problem solving, judgment </li></ul><ul><li>7.  Limitation of utilization behavior </li></ul><ul><li>8.  Frontal release sign </li></ul><ul><ul><li>a.   Snout </li></ul></ul><ul><ul><li>b.   Suck </li></ul></ul><ul><ul><li>c.   Palmomental </li></ul></ul><ul><ul><li>d.   Grasp </li></ul></ul><ul><ul><li>e.    Brow tapping </li></ul></ul>
    37. 37. Prefrontal lobe area 10
    38. 38. Inferiomedial Frontal lobe syndrome <ul><li>Orbitofrontal syndrome (disinhibited) </li></ul><ul><ul><li>Disinhibited, impulsive behaviour (pseudopsychopathic) </li></ul></ul><ul><ul><li>Inappropriate jocular affect, euphoria </li></ul></ul><ul><ul><li>e motional lability </li></ul></ul><ul><ul><li>Poor judgment and insight </li></ul></ul><ul><ul><li>Distractibility </li></ul></ul>
    39. 39. Medial frontal syndrome (akinetic) <ul><ul><li>Paucity of spontaneous movement and gesture </li></ul></ul><ul><ul><li>Sparse verbal output (repetition may be preserved) </li></ul></ul><ul><ul><li>Lower extremity weakness and loss of sensation Incontinence </li></ul></ul>
    40. 40. Frontal convexity syndrome <ul><li>Apathy (occasional brief angry or aggressive outbursts common) Indifference </li></ul><ul><li>Psychomotor retardation Motor perseveration and impersistence </li></ul><ul><li>Loss of self Stimulus-bound behaviour </li></ul><ul><li>Discrepant motor and verbal behaviour </li></ul><ul><li>Motor programming deficits </li></ul><ul><li>Three-step hand sequence Alternating programs Reciprocal programs Rhythm tapping Multiple loops </li></ul><ul><li>Poor word list generation </li></ul><ul><li>Poor abstraction and categorization </li></ul><ul><li>Segmented approach to visuospatial analysis </li></ul>
    41. 41. Premotor Cortex Area 6,8,9
    42. 42. Frontal lobe signs <ul><li>Word fluency </li></ul><ul><li>Abstract thinking </li></ul><ul><ul><li>if I have 18 books and two bookshelves, and I want twice as many books on one shelf as the other. how many books on each shelf? </li></ul></ul><ul><li>Proverb and metaphor interpretation </li></ul><ul><li>Wisconsin Card Sorting Test </li></ul><ul><li>Other sorting tasks </li></ul><ul><li>Block design </li></ul><ul><li>Maze lest </li></ul><ul><li>Hand position test (three-step hand sequence) </li></ul><ul><li>Copying tasks (multiple loops) </li></ul><ul><li>Rhythm tapping tasks </li></ul>
    43. 43. Frontal release sign <ul><li>Grasp reflex </li></ul><ul><ul><li>Forceful grapping of object on touching palm or sole </li></ul></ul><ul><li>Sucking reflex </li></ul><ul><ul><li>By touching the lips </li></ul></ul><ul><li>Groping reflex </li></ul><ul><ul><li>Involuntary following with hand/eye of moving object </li></ul></ul><ul><li>Stimulus capture </li></ul><ul><ul><li>Utilization behavior </li></ul></ul><ul><li>Snout reflex </li></ul><ul><li>Palmomental </li></ul><ul><li>Glabellar tap </li></ul>
    44. 44. Neuroanatomic correlation <ul><li>Motor </li></ul><ul><ul><li>Perseveration -> Posteriolateral dominant lobe and connection to basal ganglia </li></ul></ul><ul><ul><li>Posterior lesion -> difficulty in organizing </li></ul></ul><ul><ul><li>Anterior lesion -> dissociation between behavior and language </li></ul></ul><ul><li>Attention </li></ul><ul><ul><li>Brainstem thalamic frontal system </li></ul></ul><ul><li>Orbitofronal syndrome </li></ul><ul><ul><li>Frontolimbic link </li></ul></ul><ul><li>Loss of inhibition of parietal lobe </li></ul><ul><ul><li>Echophenomenon and environmental dependency </li></ul></ul>
    45. 45. Frontal Pathology <ul><li>Injury </li></ul><ul><li>Tumor </li></ul><ul><li>Abscess, infection </li></ul><ul><li>Dementia </li></ul><ul><li>Epilepsy </li></ul><ul><li>Stroke </li></ul><ul><li>Developmental </li></ul>
    46. 46. Frontal lobe injury <ul><li>Attention disorder – </li></ul><ul><ul><li>Distractibility </li></ul></ul><ul><li>Memory </li></ul><ul><ul><li>Poor “forgetting to remember” </li></ul></ul><ul><li>Thinking </li></ul><ul><ul><li>Concrete </li></ul></ul><ul><ul><li>Perseveration and stereotypy, </li></ul></ul><ul><ul><li>unable to switch task </li></ul></ul><ul><li>Language </li></ul><ul><ul><li>Dynamic aphasia </li></ul></ul><ul><ul><li>Normal motor speech </li></ul></ul><ul><ul><li>Normal repetition </li></ul></ul><ul><ul><li>Difficulty in prepositioning </li></ul></ul><ul><ul><li>Difficulty in structuring sentence </li></ul></ul><ul><ul><li>Lack of coherence </li></ul></ul><ul><ul><li>Socially inappropriate and disinhibited </li></ul></ul>
    47. 47. Frontal lobe injury cont. <ul><li>Mood, affect, behavior </li></ul><ul><ul><li>Reduced activity </li></ul></ul><ul><ul><li>Lack of drive and initiative </li></ul></ul><ul><ul><li>Lack of concern </li></ul></ul><ul><ul><li>Bouts of restlessness and uncoordinated behavior </li></ul></ul><ul><ul><li>Apathy, emotional blunting, indifference to the surrounding </li></ul></ul><ul><ul><li>Bouts of euphoria </li></ul></ul><ul><ul><li>Disinhibition – irritability and aggression </li></ul></ul><ul><ul><li>Witzelsucht – inappropriate facetiousness and tendency to pun </li></ul></ul>
    48. 48. Inferiomesial Frontal leukotomy <ul><li>Hours </li></ul><ul><ul><li>Drowsy </li></ul></ul><ul><ul><li>Apathetic </li></ul></ul><ul><ul><li>Incontinent </li></ul></ul><ul><ul><li>Akinetic </li></ul></ul><ul><ul><li>Mute </li></ul></ul><ul><li>Days </li></ul><ul><ul><li>Decreased initiative </li></ul></ul><ul><ul><li>Lack of concern </li></ul></ul><ul><ul><li>Freedom from anxiety </li></ul></ul><ul><ul><li>Apathetic </li></ul></ul><ul><li>Weeks to months </li></ul><ul><ul><li>Regained memory and intellect </li></ul></ul><ul><ul><li>With personality changes </li></ul></ul><ul><ul><li>Indifferent to the others problem </li></ul></ul><ul><ul><li>No thought to their conduct </li></ul></ul><ul><ul><li>Tactless </li></ul></ul><ul><ul><li>Distractible </li></ul></ul><ul><ul><li>Socially inept </li></ul></ul><ul><ul><li>Euphoria and emotional outburst </li></ul></ul>
    49. 49. Frontal lobe epilepsy <ul><li>Clinical Features </li></ul><ul><ul><li>Frequent seizure with clustering </li></ul></ul><ul><ul><li>Brief stereotyped seizure </li></ul></ul><ul><ul><li>Nocturnal attacks </li></ul></ul><ul><ul><li>Sudden onset and cessation </li></ul></ul><ul><ul><li>Absence of psychic aura </li></ul></ul><ul><ul><li>Absence of postictal confusion </li></ul></ul><ul><ul><li>Rapid evolution with awareness lost at onset </li></ul></ul><ul><ul><li>Prominent complex bilateral motor automatism involving lower limbs </li></ul></ul><ul><ul><li>Prominent ictal posturing and tonic spasm </li></ul></ul><ul><ul><li>Versive head and eye turning </li></ul></ul><ul><ul><li>Bizarre automatism </li></ul></ul><ul><ul><li>Frequent secondary generalization </li></ul></ul><ul><ul><li>Status epilepticus common </li></ul></ul><ul><li>EEG </li></ul><ul><ul><li>May show no ictal or interictal abnormality </li></ul></ul><ul><ul><li>May show bilateral spike waves </li></ul></ul><ul><ul><li>May show focal changes often widespread </li></ul></ul><ul><li>Imaging/ pathology </li></ul><ul><ul><li>Hemartoma </li></ul></ul><ul><ul><li>Benign tumors </li></ul></ul><ul><ul><li>Gliomas </li></ul></ul><ul><ul><li>Angioma </li></ul></ul><ul><ul><li>Dysplasia </li></ul></ul><ul><ul><li>Post traumatic </li></ul></ul><ul><ul><li>Atrophy </li></ul></ul><ul><ul><li>Tuberculoma </li></ul></ul><ul><ul><li>Cysticercosis </li></ul></ul>
    50. 50. Frontal lobe and Psychiatry <ul><li>Schizophrenia : </li></ul><ul><ul><li>Involving dorsolateral prefrontal cortex </li></ul></ul><ul><ul><li>affective changes, impaired motivation, poor insight. and other &quot;defect symptoms </li></ul></ul><ul><ul><li>Evidence : Neuropathologic studies, (23) in EEG studies, (24) in radiological studies using CT measures, (25) with MRI, (26) and in cerebral blood flow (CBF) studies. </li></ul></ul><ul><li>Personality disorder: Antisocial Personality disorder with impulsivity of frontal lobe </li></ul><ul><li>Attention deficit syndrome with distractibility of frontal lobe </li></ul>
    51. 51. Frontal lobe dementia <ul><li>T rouble in maintaining normal social and interpersonal functioning. </li></ul><ul><li>They may violate rules of politeness and may make inappropriate remarks. </li></ul><ul><li>They may become emotionally aroused very easily. </li></ul><ul><li>I nsensitivity – lack of consideration to others. </li></ul><ul><li>lack of restraint - stealing or unsocial behaviour </li></ul><ul><li>O bsession – </li></ul><ul><li>S exual misadventures,. </li></ul><ul><li>Kluver Bucy Syndrome </li></ul><ul><ul><li>hypersexuality, gluttony, and an obsession to touch and seize any objects in the person's field of vision. Overeating may lead to considerable weight gain. </li></ul></ul><ul><li>Language Problems </li></ul><ul><ul><li>limited speech output, lack of speech spontaneity, stereotyping of phrases (ie., use of pat phrases repeatedly and excessively), perseveration (a meaningless persistence of verbal activity), a decreased vocabulary, a considerable amount of repetition, especially of brief words and phrases. </li></ul></ul><ul><ul><li>Often there is jargon and instead of being able to find the word to describe an object, the person with this disease will give a description of it instead (ie., a &quot;watch&quot; referred to as &quot;something you tell the time with&quot;). This means that the person may not be able to name objects early in the disease. </li></ul></ul><ul><ul><li>Eventually the person becomes mute for periods and then completely mute by the end of the disease. </li></ul></ul>
    52. 52. Frontal lobe pathology Frontal lobe abscess Meningioma
    53. 53. Frontal pathology Frontal glioblastoma Tuberous sclerosis
    54. 54. Thank You

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