OUTLINE Introduction Functional anatomy of the frontal lobes Neurotransmitters in the frontal lobes Frontotemporal Dementia Frontal lobe syndrome Frontal lobe epilepsy Schizophrenia & Frontal lobe Depression & frontal lobe Testing prefrontal cortical function Common causes of frontal lobe syndromes
Complexity of the Brain… one hundred trillion synapsesin a single human brainorganized into exquisitely complex circuits…responding to experience, drugs,disease, and injury…
Complexity of the BrainAs befits the 3-pound organ of themind, the human brain is the mostcomplex structure ever investigatedby our science.
It is useful to think of the brain as containing six orseven component parts. The largest and mostadvanced part consists of the left and right cerebralhemispheres, which appear to be more or lesssymmetrical. They are covered with a layer of graymatter called the cerebral cortex. Each of the cerebralhemispheres has traditionally been divided into four"lobes," which are named after the bones of the skullthat surround them: frontal, parietal, occipital, andtemporal.
The frontal lobe is the largest and least understood, beginning atthe front of the brain and reaching back to the central sulcus &laterely lateral sulcus. The area between the central andprecentral sulci helps control body movements and is called the"motor area," while the remainder of the frontal lobe probablymodulates various aspects of thinking, feeling, imagining, andmaking decisions.
FUNCTIONAL FRONTAL LOBE ANATOMY Largest of all lobes SA: ~1/3 of each hemisphere 3 major areas in each lobe Dorsolateral aspect Medial aspect Inferior orbital aspect
FUNCTIONAL FRONTAL LOBE ANATOMY Premotor area Primary motor area B6 B4 Central sulcus Supplementary motor area (medially) Frontal eye field B8 Prefrontal area B 9, 10, 11, 12 Lateral sulcus/ Sylvian fissure Motor speech area of Broca B 44, 45
FUNCTIONAL FRONTAL LOBE ANATOMY Motor cortex Prefrontal cortex Primary – Dorsolateral Premotor – Medial Supplementary – Orbitofrontal Frontaleye field Broca‟s speech area
MOTOR CORTEX Primary motor cortex Input: thalamus, BG, sensory, premotor Output: motor fibers to brainstem and spinal cord Function: executes design into movement Lesions: / tone; power; fine motor function on contra lateral side
MOTOR CORTEX Premotor cortex Input:thalamus, BG, sensory cortex Output: primary motor cortex Function: stores motor programs; controls coarse postural movements Lesions: moderate weakness in proximal muscles on contralateral side
MOTOR CORTEX Supplementary motor Input:cingulate gyrus, thalamus, sensory & prefrontal cortex Output: premotor, primary motor Function: intentional preparation for movement; procedural memory Lesions: mutism, akinesis; speech is non- spontaneous
MOTOR CORTEX Frontal eye fields Input: parietal / temporal (what is target); posterior / parietal cortex (where is target) Output: caudate; superior colliculus; paramedian pontine reticular formation Function: executive: selects target and commands movement (saccades) Lesion: eyes deviate ipsilaterally with destructive lesion and contralaterally with irritating lesions
MOTOR CORTEX Broca‟s speech area Input:Wernicke‟s Output: primary motor cortex Function: speech production (dominant hemisphere); emotional, melodic component of speech (non-dominant) Lesions: motor aphasia; monotone speech
PREFRONTAL CORTEX Orbital prefrontal cortex Connections: temporal,parietal, thalamus, GP, caudate, SN, insula, amygdala Part of limbic system Function: emotional imput, arousal, suppression of distracting signals Lesions: emotional lability, disinhibition, distractibility, „hyperkinesis‟
FRONTAL SUBCORTICAL CIRCUITS:1. MOTOR CIRCUIT Globus SMA, Pallidus Hypo-thalamus Premotor,Mo Putamen tor Thalamus Supplementary Motor & Premotor: planning, initiation & storage of motor programs; fine-tuning of movements Motor:final station for execution of the the movement according to the design
FRONTAL SUBCORTICAL CIRCUITS:2. OCULOMOTOR CIRCUIT Globus Frontal Eye Pallidus Central Thalamus Field Caudate Substantia Nigra Voluntary scanning eye movement Independent of visual stimuli
FRONTAL SUBCORTICAL CIRCUITS:3. DORSOLATERAL PREFRONTAL CIRCUIT GlobusLateral Pallidus Caudate ThalamusPrefrontal Substantia Nigra Executive functions: motor planning, deciding which stimuli to attend to, shifting cognitive sets Attention span and working memory
Frontal Lobe SyndromesThe Case of Phineas Gage tamping iron blown through skull: L frontal brain injury excellent physical recovery dramatic personality change: stubborn, lacked in consideration for others, had profane speech, failed to execute his plans
FRONTOTEMPORAL LOBE DEMENTIA Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disease that selectively attacks the frontal and anterior temporal regions. FTLD occurs in 5–15% of patients with dementia and it is the third most common degenerative dementia, following only Alzheimer‟s disease (AD) and dementia with Lewy bodies. Typical age of onset is between 50 and 60 years, although FTLD can occur as early as the 20s and has been reported in the ninth decade.
FRONTOTEMPORAL LOBE DEMENTIA In contrast to AD, in which memory loss is usually the first symptom, the initial symptoms of FTLD often involve changes in personality, behavior, affective symptoms, and language function. Most patients with FTLD begin with language (left- sided cases) or emotional (right-sided cases) changes. The lack of insight seen in FTLD,leads patients to ignore or deny their deficits. The core features of FTLD as defined by the Neary criteria (Neary et al., 1998) are early decline in social and personal conduct, emotional blunting, and loss of insight.
FRONTOTEMPORAL LOBE DEMENTIA The clinical onset is insidious, with a slow gradual progression. Although the neuropsychiatric profile for patients with FTLD varies. Behavior problems such as overeating, repetitive compulsive behaviors, apathy, and agitation and disinhibition, develop in the majority of these patients as the disease progresses. The estimated duration of the illness is around 6–10 years. SSRI improved a variety of psychiatric symptoms, including irritability, depression, repetitive behaviors, and hyperorality.
FRONTAL LOBE SYNDROMES The dorsolateral frontal cortex is concerned with planning, strategy formation, and executive function. Patients with dorsolateral frontal lesions tend to have apathy, personality changes, abulia, and lack of ability to plan or to sequence. patients have poor working memory for verbal information (if the left hemisphere is predominantly affected) or spatial information (if right hemisphere lesion). The frontal operculum contains the center for expression of language. Patients with left frontal operculum lesions may demonstrate Broca aphasia and defective verb retrieval, whereas patients with exclusively right opercular lesions tend to develop expressive aprosodia.
The orbitofrontal cortex is concerned with response inhibition. Patients with orbitofrontal lesions shows disinhibition, emotional lability, and memory disorders. Personality changes from orbital damage include impulsiveness, a jocular attitude, sexual disinhibition, and complete lack of concern for others. Patients with superior mesial lesions typically develop akinetic mutism. Patients with inferior mesial (basal forebrain) lesions tend to manifest anterograde and retrograde amnesia and confabulation.
CAUSES Mental retardation Traumatic brain injury Brain tumors Degenerative dementias including Alzheimer disease, dementia with Lewy bodies, Parkinsonian dementias, and frontotemporal dementias Cerebrovascular disease Schizophrenia major depression multiple sclerosis It is associated with blood alcohol level and occurs during acute intoxication with many recreational drugs.
CLINICAL PICTURE Profound change in personality. Lack of initiation and spontanity. Response are sluggish. Occasionally patient are hyperactive and restless. Mood is often euphoric and out of keeping with patients situation. Irritability and outbursts are common. Loss of finer senses. Judgements are impaired. Fail to plan and carry through ideas.
FRONTAL LOBE EPILEPSY Frontal lobe epilepsy is characterized by recurrent seizures arising from the frontal lobes. Seizures may arise from any of the frontal lobe areas, including orbitofrontal,dorsolateral, opercular, supplementary motor area, motor cortex, or cingulate gyrus. In most centers frontal lobe epilepsy accounts for 20-30% of operative procedures involving intractable epilepsy. No significant gender-based frequency. In a large series of cases, mean subject age was 28.5 years with age of epilepsy onset 9.3 years for left frontal epilepsy and 11.1 years for right frontal epilepsy.
CLINICAL PICTURE Patients with frontal lobe seizures may present with a clear epileptic syndrome or with unusual behavioral or motor manifestations that are not immediately recognizable as seizures. may be associated with facial grimacing, vocalization, or speech arrest. seizures frequently preceded by a somatosensory aura. Complex behavioral events characterized by motor agitation and gestural automatisms; viscerosensory symptoms and strong emotional feelings often described; motor activity and may involve pelvic thrusting, pedaling, or thrashing, often accompanied by vocalizations or laughter/crying; seizures often bizarre and may be diagnosed incorrectly as psychogenic
EXPRESSIVE APHASIA Expressive aphasia, known as Brocas aphasia caused by damage or developmental issues in anterior regions of the brain, including the left posterior inferior frontal gyrus known as Brocas area (Brodmann area 44and Brodmann area 45). Sufferers of this form of aphasia exhibit the common problem of agrammatism. For them, speech is difficult to initiate, non- fluent, labored, and halting. Similarly, writing is difficult as well. Intonation and stress patterns are deficient. Language is reduced to disjointed words and sentence construction is poor. comprehensionis generally preserved, meaning interpretation dependent on syntax and phrase structure is substantially impaired. Patients who recover go on to say that they knew what they wanted to say but could not express themselves. Residual deficits will often be seen.
SCHIZOPHRENIA & FRONTAL LOBE some schizophrenic symptoms are found in frontal lobe disorder, in particular that involving dorsolateral prefrontal cortex. Symptoms included are those of the affective changes, impaired motivation, poor insight. Evidence for frontal lobe dysfunction in schizophrenic patients has been noted in neuropathologic studies like EEG studies, in CT scan, with MRI, and in cerebral blood flow studies. Hypofrontality is documented in several studies using PET. These findings emphasize the importance of neurologic and neuropsychologic investigation of patients with schizophrenia.
DEPRESSION & FRONTAL LOBE it has been found that the right frontal lobe demonstrated increased activity in response to negative moods whereas left frontal activity decreases. repetitive transcranial magnetic stimulation of the right frontal lobe reduces depressive symptoms , whereas left frontal activity increase depression as demonstrated through functional imaging studies. Not only reductions in left frontal activity, but injuries to the left frontal lobe have been consistently associated with depression, "psycho-motor" retardation, apathy, irritability, and blunted mental functioning. psychiatric patients classified as depressed demonstrate insufficient left frontal activation and arousal. In severely depressed patients demonstrate insufficient activation and a significant lower integrated amplitude of the EEG evoked response over the left vs right frontal lobe.
Testing for Frontal lobe function– Wisconsin Card Sorting Test • abstract thinking and set shifting; L>R– Trail Making • visuo-motor track, conceptualization, set shift– Stroop Color & Word Test • attention, shift sets; L>R– Tower of London Test • planning
Wisconsin Card Sorting Test“Please sort the 60 cards under the 4 samples.I won‟t tell you the rule, but I will announce every mistake.The rule will change after 10 correct placements.”
Trail Making Test 5 B A 4 6 1 C 2 3 D 7Various levels of difficulty:1. “Please connect the letters in alphabetical order as fast as you can.”2. “Repeat, as in „1‟ but alternate with numbers in increasing order”
Stroop Color and Word TestsRED BLUE ORANGE YELLOWGREEN RED PURPLE REDGREEN YELLOW BLUE REDYELLOW ORANGE RED GREENBLUE GREEN PURPLE RED“Please read this as fast as you can”
Tower of London TestsVarious levels of difficulty:e.g. “Please rearrange the balls on the pegs, so that each peg hasone ball only. Use as few movements as possible”
Diseases CommonlyAssociated With Frontal LobeLesions Traumatic brain injury – Gunshot wound – Closed head injury • Widespread stretching and shearing of fibers throughout • Frontal lobe more vulnerable – Contusions and intracerebral hematomas
Diseases CommonlyAssociated with Frontal LobeLesions Frontal Lobe seizures – Usually secondary to trauma – Difficult to diagnose: can be odd (laughter, crying, verbal automatism, complex gestures)
Diseases CommonlyAssociated With Frontal LobeLesions Vascular disease – Common cause especially in elderly – ACA territory infarction • Damage to medial frontal area – MCA territory • Dorsolateral frontal lobe – Anterior Communicating artery aneurysm rupture • Personality change, emotional disturbance
Diseases CommonlyAssociated With Frontal LobeLesions Tumors – Gliomas, meningiomas – subfrontal and olfactory groove meningiomas: profound personality changes and dementia Multiple Sclerosis – Frontal lobes 2nd highest number of plaques – euphoric/depressed mood, Memory problems, cognitive and behavioral effects