Impairments of Brain and Behavior

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Impairments of Brain and Behavior

  1. 1. Impairments of Brain and Behavior The Neurological Effects of Alcohol MARLENE OSCAR-BERMAN, PH.D., BARBARA SHAGRIN, PH.D., DENISE L. EVERT, PH.D., AND CHARLES EPSTEIN, PH.D. Chronic heavy drinking and alcoholism can have serious repercussions for the functioning of the entire nervous system, particularly the brain. These effects include changes in emotions and personality as well as impaired perception, learning, and memory. Neuropathological and imaging techniques have provided evidence of physical brain abnormalities in alcoholics, such as atrophy of nerve cells and brain shrinkage. At the cellular level, alcohol appears to directly affect brain function in a variety of ways, primarily by interfering with the action of glutamate, gamma-aminobutyric acid, and other neurotransmitters. Neurological disorders also can result from vitamin deficiency and liver disease, two health problems that commonly occur with alcoholism. Other hypotheses, based on factors such as aging, gender, and genetics, have been developed to explain various alcohol-related neurological consequences. Many pharmacological treatments to improve neuropsychological functioning in alcoholics have been tested, but none has proved entirely successful. With prolonged abstinence, however, slow recovery of cognitive functioning can occur in some cases. KEY WORDS: chronic AODE (alcohol and other drug effects); AODR (alcohol and other drug related) disorder; brain function; brain damage; nervous system disorder; brain imaging; neuropsychological assessment; cognitive process; emotion; memory; learning; personality; neurotransmitters; patient family history; malnutrition; liver disorder; aging; gender differences; drug therapy; hypothesis testing; literature review A lcohol consumption can damage body organs (e.g., the liver) that subse- al. 1995). For example, MRI and CT the nervous system, including quently interferes with the workings of images have shown brain shrinkage the brain. Consequently, alco- nerve cells in the brain (see figure 1). and tissue damage (i.e., brain lesions) holics1 and chronic heavy drinkers can Images of the brain created with in some alcoholics. These changes can suffer abnormalities in their mental modern neuroradiological techniques, cause poor temperature regulation, functioning and changes in behaviors such as magnetic resonance imaging associated with brain impairment. The (MRI) and computed tomography 1 The term “alcoholism” as used in this article neurological effects of alcohol can (CT), generally show a relationship refers to the criteria for alcohol dependence defined in the American Psychological occur directly, because alcohol is a between prolonged alcohol consump- Association’s Diagnostic and Statistical toxic substance, or they can occur tion and changes in the brain’s struc- Manual of Mental Disorders, Fourth Edition indirectly, through damage to other ture (Charness 1993; Pfefferbaum et (DSM–IV). VOL. 21, NO. 1, 1997 65
  2. 2. muscle weakness, and alterations in sleep patterns. This article reviews some of the Alcohol and alcoholism physical brain changes and neuropsy- chological2 consequences of alco- holism, beginning with the effects of chronic alcoholism on memory and other cognitive functions. This discus- Pharmacological sion is followed by an examination of Direct Withdrawal Nutritional Liver Head injury Unknown the differences among people that toxic effects syndromes deficiency disease commonly contribute to the many neurological effects of alcoholism, including medical health, age, gender, and family history of alcoholism. The article concludes with a consideration of treatment and recovery. Adverse effects on the nervous system COMMON EFFECTS OF ALCOHOL Figure 1 Sources of neurological complications of alcohol and alcoholism. ON THE NERVOUS SYSTEM SOURCE: Adapted from Bernat, J.L., and Victor, M. The Neurological Complications of Alcohol and Alcohol has effects on both major Alcoholism. Unit 7. 2d ed. Developed by the Project Cork Institute at Dartmouth Medical School. Timonium, MD: Milner-Fenwick, 1994. components of the nervous system— the central nervous system (i.e., the brain and the spinal cord) and the peripheral nervous system (i.e., the fulness, it often produces vivid hallu- nerves in the rest of the body). cinations. Most people fall asleep MARLENE OSCAR-BERMAN, PH.D., is a Alcohol can have a negative effect easily after one or more alcoholic professor in the departments of psy- on certain neurological processes, drinks3 but experience diminution of chiatry and neurology, Boston such as temperature regulation, sleep, REM sleep. Drinkers who attempt to University School of Medicine, and a and coordination. For example, mod- use alcohol as a sedative seldom attain research scientist in the Psychology erate amounts of alcohol lower body a full night’s sleep, however; after Research Service, Department of temperature. Severe intoxication in a several hours, the natural elimination Veterans Affairs Medical Center, cold environment may produce mas- of alcohol from the body produces Boston, Massachusetts. sive, life-threatening declines in tem- arousal and sleep fragmentation. BARBARA SHAGRIN, PH.D., is a clinical perature (i.e., hypothermia). Many When chronic drinkers withdraw from assistant professor of psychiatry, people mistakenly believe that alcohol alcohol, long-suppressed REM sleep Boston University School of can help warm them in cold weather. may rebound excessively. Some au- Medicine, Boston, Massachusetts. This notion can be especially danger- thorities (Greenberg and Pearlman ous for the homeless, for elderly peo- 1967) believe that delirium tremens DENISE L. EVERT, PH.D., is a research ple living in inadequately heated (known as DT’s), a condition occur- associate in the department of psychi- quarters, and for those exposed to ring 2 to 4 days after alcohol with- atry, Harvard Medical School, prolonged cold temperatures outdoors. drawal that consists of trembling and Boston, Massachusetts. In addition to its effect on body agitation with hallucinations, overex- CHARLES EPSTEIN, PH.D., is associate temperature, alcohol interferes with citation, fever, sweating, and rapid professor of neurology and director of normal sleep patterns. Relatively heartbeat, represents a state of contin- clinical neurophysiology, Emory small doses of alcohol can cause early uous REM sleep. In addition, measur- University School of Medicine, sedation or sleepiness, awaking during able insomnia may occur many weeks Atlanta, Georgia. the night, and suppression of rapid- into abstinence. eye-movement (REM) sleep. REM Another prominent effect of chronic The writing of this article was support- sleep is the dreaming stage of sleep; alcohol consumption is harm to the ed by National Institute on Alcohol when REM sleep occurs near wake- part of the brain called the cerebellum Abuse and Alcoholism grants R37- AA07112 and K05-AA00219 and by 2 Neuropsychology is the branch of psychology 3 One standard drink is defined as 12 fluid the Medical Research Service of the focused on the study of the relationship be- ounces (oz) of beer, 5 fluid oz of wine, or 1.5 U.S. Department of Veterans Affairs. tween the brain and behavior. fluid oz of distilled spirits. 66 ALCOHOL HEALTH & RESEARCH WORLD
  3. 3. Brain and Behavior Impairments United States is Dwight Eisenhower or John Kennedy. Some alcoholics Cerebral cortex may have a genetic component or Cerebrum predisposition to develop this am- Corpus callosum nesic condition: These patients may Parietal lobe have an enzyme deficiency that pre- Frontal lobe vents their bodies from using thi- amine (a B vitamin) efficiently.4 This deficiency, coupled with a diet high in alcohol and low in thiamine Lateral (along with other nutrients), may ventricle lead to brain damage causing the Thalamus amnesia. Although KS destroys short-term Hypothalamus memory, it typically spares most long- term memories (i.e., memories formed Temporal lobe or knowledge gained before the onset Cerebellum Pituitary gland Mammillary body of prolonged heavy drinking). Thus, overall intelligence, as measured by Brain stem standardized IQ tests, does not neces- sarily deteriorate, because the types of Figure 2 Schematic of a lengthwise cross-section through the human brain. Brain information and abilities tapped by structures that most frequently have been implicated in alcohol-related these tests usually involve long-term neurological disorders include parts of the diencephalon (i.e., the memory. mammillary bodies of the hypothalamus and the dorsomedial nucleus within the thalamus), the cerebral cortex, and several central neuro- transmitter (i.e.,nerve cell communication) systems. Other Neuropsychological Problems (figure 2), resulting mainly in the loss cialized neuropsychological tests. Within the past 25 years, clinical and of muscular coordination. This damage Behavioral neurologists and neuropsy- experimental observations of patients appears as imbalance and staggering, chologists use these sensitive tests to with and without KS have revealed although other problems also may measure both the obvious and the many other neuropsychological dys- occur (Raymond et al. 1996). subtle consequences of brain damage. functions associated with alcoholism. A peripheral nervous system disor- Results of the tests often show changes Alcoholics demonstrate poor attention der commonly seen in alcoholics is in emotions and personality as well as to what is going on around them; need numbness and weakness in the hands impaired perception, learning, and extra time to process visual informa- and feet (i.e., peripheral neuropathy). memory (i.e., cognitive abilities) after tion; have difficulty with abstraction, This condition is thought to be largely damage to particular brain systems problem-solving, and learning new a consequence of malnutrition in se- (see Evert and Oscar-Berman 1995). materials; exhibit emotional abnor- vere alcoholics. One type of peripheral malities and disinhibitions; and show nerve damage known as Saturday night Korsakoff’s Syndrome reduced visuospatial abilities (i.e., the palsy can occur when an alcoholic puts capacity to deal with objects in two- pressure on vulnerable nerves in the One of the most severe consequences arm while lying in an intoxicated stu- of long-term alcoholism on mental 4 Another disorder, Wernicke’s encephalopathy, functioning is Korsakoff’s syndrome frequently occurs with KS, leading to a diagno- por, leaving him or her unable to ex- sis in the patient of Wernicke-Korsakoff (KS), a devastating memory disorder tend the wrist for days to weeks. syndrome. Patients with Wernicke’s in which a person appears to forget encephalopathy exhibit confusion, uncoordi- the incidents of his or her daily life nated gait, and abnormal eye movements, and as soon as they occur (see Oscar- imaging techniques reveal lesions in the ABNORMALITIES IN NEUROPSYCH- diencephalon, the cerebellum, and the brain OLOGICAL FUNCTIONS Berman 1990). Because of this dra- stem. Like KS, Wernicke’s encephalopathy is matic loss of short-term memory thought to be caused by a thiamine deficiency; In addition to changes in temperature (also called anterograde amnesia), the syndrome’s acute manifestations often can regulation, sleep, and coordination, patients with KS virtually live in the be reduced by thiamine administration. Hospitalized alcoholics being administered alcoholism-related brain changes can past. For example, someone who intravenous glucose also should receive thi- cause abnormalities in mental func- developed KS in the 1960’s might amine to reduce the possibility of developing tioning that are detectable using spe- believe that the President of the acute Wernicke’s encephalopathy. VOL. 21, NO. 1, 1997 67
  4. 4. dimensional or three-dimensional cells (i.e., neurons) and brain shrink- smell (i.e., olfaction), and the ability space) (Parsons and Nixon 1993). The age (Hunt and Nixon 1993). Brain to use one sense (e.g., vision) to learn once-common view that alcoholics shrinkage appears as abnormal widen- something in another sense (e.g., without Korsakoff’s syndrome are ing of the grooves (i.e., sulci) and touch) (i.e., cross-modal functioning). cognitively intact has been abandoned fissures on the brain’s surface or en- In all these categories of function, in light of accumulating evidence that largement of the fluid-filled cavities researchers have observed deficits in cognitive impairments (and associated deep inside the brain (i.e., the ventri- alcoholics (Evert and Oscar-Berman changes in brain structure) can occur cles). Regions of the brain that are 1995). Moreover, alcoholics with KS in alcoholics who do not exhibit obvi- especially vulnerable to damage after appear to have greater impairment in ous clinical signs of anterograde am- years of chronic alcoholism include some of these functional areas than do nesia (see Lishman 1990). the cerebellum, the limbic system non-KS alcoholics. (including the hippocampus and amyg- dala), the diencephalon (including the The Diencephalon ALCOHOLISM-RELATED BRAIN thalamus and hypothalamus), and the DAMAGE AND ASSOCIATED cerebral cortex (see figures 2 and 3). The diencephalon, a region nestled in NEUROPSYCHOLOGICAL CHANGES Countless intricate pathways of the center of the brain, acts like a way neurons link the different areas of the station for nerve signals moving from The type and extent of structural brain, including the regions implicat- one area of the brain to another. Al- damage to brain tissue can be deter- ed in alcohol-related neurological though it is not known precisely what mined by autopsy (i.e., post mortem) dysfunction. Because of the size and role diencephalic structures play in examination of the brain’s compo- complexity of this network, the con- human memory functioning, lesions in nents and individual nerve cells (i.e., sequences of damage to one structure this region have been clearly docu- neuropathological evidence). In addi- or system often can resemble the con- mented in amnesic patients (Victor et tion, neuroradiological techniques, sequences of damage to another. The al. 1989). Researchers are not certain such as MRI and CT scans, allow the following sections describe alcohol- whether alcohol-related memory im- brain to be viewed inside the skull of related structural and neuropsycho- pairments are caused by these lesions, a living person. Other neuroimaging logical changes that can occur in the however. An alternative explanation techniques (i.e., functional neuro- brain. comes from a study that compared imaging) measure active brain func- MRI measures of diencephalic dam- tioning. Functional neuroimaging can The Limbic System age in alcoholics with and without KS reveal changes in the blood flow in (Blansjaar et al. 1992). The authors and around the brain, brain metab- The limbic system is an intricate net- suggested that diencephalic lesions olism, and brain electrical activity work of structures located deep inside develop regardless of whether patients generated by nerve impulses (i.e., the brain; its functions are diverse and acquire the amnesia of KS and are not neurophysiological measures).5 One varied. One function of the limbic sys- so much typical of KS as they are of type of neurophysiological measure, tem receiving attention from alcohol chronic alcoholism and malnutrition. event-related potentials (ERP’s), researchers is memory. Memory loss consists of brain waves recorded from similar to the amnesia in KS patients The Cerebral Cortex scalp electrodes while a person is has been associated with damage to presented with specific pieces of the hippocampus and the amygdala, The cerebral cortex is the intricately information or stimuli. Scientists use parts of the limbic system that are folded outer layer of the brain com- computers to translate the information located in the temporal lobes of the posed of nerve cell bodies (i.e., gray obtained from ERP’s and other func- brain (see Evert and Oscar-Berman matter). It is considered to be the tional neuroimaging measures into 1995). Although injury to the limbic center of higher consciousness and the meaningful pictures that, in turn, system can cause amnesia, researchers seat of all intelligent behavior. The make it possible to view brain func- are not certain of the degree to which cortex makes neural connections, both tioning while a person is thinking or alcohol-related memory impairments directly and indirectly, with all parts performing a task. may be linked to damage in that part of the nervous system and, therefore, When applied to alcohol research, of the brain. with all parts of the body. neuropathological and imaging tech- Alcohol researchers are interested As noted previously, neuroradio- niques have helped to provide cumula- in other functions of the limbic system logical evidence has revealed a tive evidence of brain abnormalities in as well. Damage to certain parts of the widening of the fissures and sulci of alcoholics, such as atrophy6 of nerve limbic system leads to abnormalities the cerebral cortex and enlargement in emotional functioning, the sense of of the ventricles in brains of alco- 5 For additional information on imaging tech- holics. These changes suggest corti- niques in alcohol research, see Alcohol Health 6 For definitions of this and other technical cal atrophy associated with & Research World Vol. 19, No. 4, 1995. terms, see glossary, pp. 93–96. alcoholism (Pfefferbaum and 68 ALCOHOL HEALTH & RESEARCH WORLD
  5. 5. Brain and Behavior Impairments Rosenbloom 1993; Pfefferbaum et al. 1995). The evidence for cortical atrophy has come both from imaging Corpus callosum studies of detoxified alcoholics and from post mortem analyses of the Anterior nucleus brains of alcoholics. For example, of the thalamus MRI findings show evidence of sig- Dorsomedial nificant cortical and subcortical tis- Thalamus nucleus sue and volume loss in non-KS of the alcoholics compared with nonalco- thalamus holic control subjects. Moreover, alcoholics with KS have greater cor- tical atrophy than non-KS alcoholics. Researchers also have reported neu- ropsychological deficits in alcoholics Amygdala (e.g., through tests of problem-solv- ing, spatial memory, visual associa- tions, and learning related to or Temporal lobe Mammillary caused by touch [i.e., tactual learn- body Third ventricle ing]) that indicate alcoholism-related cortical atrophy (Evert and Oscar- Hippocampus Berman 1995). In most studies of alcohol-related Figure 3 Schematic of a cross-section through the human brain. Brain structures neurological disorders, researchers that have been implicated in alcohol-related neurological disorders have assessed neuropsychological include parts of the limbic system (i.e., the hippocampus and the deficits in alcoholics without examin- amygdala), the mammillary bodies of the hypothalamus, and the ing changes in alcoholics’ brains. To dorsomedial nucleus within the thalamus. better understand brain-behavior rela- SOURCE: Adapted from Nieuwenhuys, R.; Voogd, J.; and van Huijzen, C. The Human Central tionships, however, neuropsychologi- Nervous System: A Synopsis and Atlas. New York: Springer Verlag, 1988. cal, structural, and functional changes must be evaluated to relate changes in behavior to damage in particular sys- lics, based on functional and struc- In studies of KS patients, re- tems of the brain. In studies using both tural imaging techniques, have been searchers have obtained additional methods, in fact, results have not re- abnormalities in frontal brain regions findings supporting frontal-system vealed consistent relationships between (for reviews, see Oscar-Berman and dysfunction (Oscar-Berman and cortical damage and performance on Hutner 1993; Pfefferbaum and Hutner 1993). Neuropsychological neuropsychological tests. Some mea- Rosenbloom 1993). Frontal-system studies have shown that KS patients sures of brain structure or function functions include planning, carrying have correlated with cognitive test exhibit clinical signs associated with out, and monitoring goal-directed damage to the frontal cortex (e.g., scores, whereas others have not. For and socially suitable behaviors. example, one study reported a relation- emotional apathy, personality Compared with nonalcoholic control changes and loss of inhibitions, and ship between certain neuropsychologi- subjects, some alcoholics have shown cal test scores and measures of frontal constant repetition of certain respons- significant reductions in cerebral brain metabolism in long-term alco- es despite feedback indicating that blood flow in certain areas of the holics; the same study, however, found such responses are incorrect or inap- no correlation between neuropsycho- frontal regions as well as in other brain areas. In addition, greater blood propriate [i.e., abnormal response logical performance and degree of perseveration]). Although much de- cortical atrophy as seen using MRI flow reduction in frontal cortical areas has been associated with bate centers on the connection between (Wang et al. 1993). The results were greater severity of alcoholism and measures of alcohol consumption and interpreted as reflecting either the preser- vation of cognitive abilities with mild poorer cognitive test performance. In the degree of structural or functional structural brain changes or the insensi- other studies, alcoholics showed impairment in non-KS alcoholics, tivity of the tests used to detect mild diminished metabolic functions in research so far has failed to demon- structural changes. frontal areas; this reduction was asso- strate a clear connection between The most consistently and fre- ciated with impaired neuropsycho- measures of alcohol intake, cognitive quently reported findings in alcoho- logical functions. dysfunction, and frontal damage. VOL. 21, NO. 1, 1997 69
  6. 6. NEUROTRANSMITTERS AND for the short-lived condition referred the memory deficits of patients with ALCOHOLISM to as “alcoholic blackout.” Because of KS [NIAAA 1993]), have been less its inhibitory effect on glutamate, consistently observed. At the cellular level, alcohol appears to chronic consumption of alcohol leads Alcohol disrupts neuron activity in affect brain function in a variety of to up-regulation of glutamate receptor various other ways. For example, over ways. For example, alcohol can alter sites in the hippocampus, an area that several weeks, alcohol reduces the the action of the chemicals that allow is crucial to memory and often in- level of nerve growth factors, proteins neurons to communicate (i.e., neuro- volved in epileptic seizures. During important for cellular adaptation and transmitters). Specialized proteins on alcohol withdrawal, glutamate recep- survival. In addition, alcohol may the surface of neurons, known as recep- tors that have adapted to the continual cause long-term adaptive changes in tors, recognize neurotransmitters and presence of alcohol may become membrane lipids. initiate the cell’s response. Neuro- overactive. Glutamate overactivity has transmitters and receptors cluster where been linked repeatedly to cell death in nerve cells come into close contact; situations ranging from strokes to VULNERABILITIES TO THE these contacts are called synapses. seizures. Deficiencies of thiamine and NEUROLOGICAL EFFECTS Some neurotransmitters stimulate (i.e., magnesium, which are common in OF ALCOHOLISM excite) a response from the neurons that alcoholics as a result of malnutrition, receive them; others inhibit neuronal Alcoholism is a multidimensional may contribute to this potentially response. Over periods of days and disorder, and no simple answers exist destructive overactivity. weeks, the levels of receptors change in to questions such as: “What are the response to chemical and environmen- neurological consequences of alco- GABA holism?”; “What makes alcoholism tal influences (e.g., drugs and synaptic activity) on the neurons. Genes in the Gamma-aminobutyric acid (GABA) is affect different people in different neuron’s DNA are turned on or off, the major inhibitory neurotransmitter ways?”; or even “What causes some- increasing or decreasing the synthesis in the central nervous system. one to become an alcoholic in the first of receptors. Over time, drugs that Evidence suggests that alcohol initial- place?” Widespread individual differ- excite a given receptor generally lead to ly potentiates GABA effects; in other ences occur in the manifestation of a reduction in (i.e., down-regulate) the words, it increases inhibition, and alcoholism. For example, according to numbers or activity of that receptor often the brain becomes mildly sedat- one estimate, 50 to 85 percent of non- type. Drugs that inhibit a receptor even- ed. But over time, chronic alcohol KS alcoholics exhibit signs of cogni- tually tend to lead to an increase in (i.e., consumption reduces the number of tive decline (see Parsons 1993). Thus, up-regulate) that type of receptor. Up- GABA receptors through the process anywhere from 15 to 50 percent of and down-regulation are means by of down-regulation. When alcohol is such alcoholics may not exhibit any which the nervous system maintains a eventually withdrawn, the loss of its obvious signs of cognitive impairment. functional balance of neurotransmitters inhibitory effects, combined with a In general, the greater the consumption and receptors; when imbalances occur, deficiency of GABA receptors, may of alcohol, the worse the performance effects can include seizures, sedation, contribute to overexcitation through- on cognitive tasks. However, among depression, agitation, and other mood out the brain. This effect, in turn, can those alcoholics who exhibit neurologi- and behavioral disorders. contribute to withdrawal seizures (i.e., cal problems, researchers have found “rum fits”) within 1 or 2 days. that measures of previous alcohol Glutamate consumption (e.g., duration, frequency, Other Neurotransmitters and quantity consumed) do not corre- The major excitatory neurotransmitter late consistently with the degree of in the human brain is glutamate, an Alcohol directly stimulates release of neuropsychological dysfunction amino acid. Glutamate has a funda- the neurotransmitter serotonin as well (Parsons 1993). This finding suggests mental role in a cellular adaptation as natural substances related to opi- that variables other than the presumed called long-term potentiation, which is oids (i.e., endorphins) that may con- direct neurotoxic effects of alcohol a persistent increase in the efficiency tribute to the “high” of intoxication. may play a role in determining alcohol- of a neuron’s response to a neuro- Serotonin helps regulate functions related cognitive decline. In response transmitter. Long-term potentiation such as food and water intake, sexual to the variability in the consequences may be an important mechanism in response, and aggression. Changes in of alcoholism, researchers have looked learning and memory. other neurotransmitters, such as for common elements that might help Extremely small amounts of alco- acetylcholine (which underlies key explain why certain alcoholics develop hol have been shown to interfere with cardiovascular mechanisms, including specific neurological symptoms or glutamate action. This interference dilation of blood vessels) and the mental changes. Factors that may influ- could affect multiple brain functions, catecholamines (the decreased trans- ence the neurological consequences of including memory, and it may account mission of which has been linked to alcoholism include coexisting health 70 ALCOHOL HEALTH & RESEARCH WORLD
  7. 7. Brain and Behavior Impairments problems, such as malnutrition and people will exhibit severe anterograde which premature aging begins (for liver disease; the age at which problem amnesia as well as other cognitive reviews, see Ellis and Oscar-Berman drinking begins; the gender of the impairments. 1989; Evert and Oscar-Berman 1995). alcoholic; and a family history of alco- According to the accelerated aging holism. These factors are considered in Liver Disease version of the hypothesis, aging starts the sections that follow. to accelerate at whatever age problem Alcohol-related liver disease also drinking begins. This version predicts contributes to neurological distur- that young alcoholics will become old COMMON ALCOHOL-RELATED bances associated with heavy drinking before their time and that neuropsy- MEDICAL PROBLEMS (Tarter et al. 1993). The risk of alco- chological and brain changes in alco- holic liver damage depends on factors holics will mimic those found in Two common health problems occur- such as the drinker’s nutrition, gender, chronologically older nonalcoholics. ring with alcoholism are vitamin defi- and quantity and pattern of alcohol According to the increased vulnera- ciency and liver disease, both of consumption. Recent research (Tarter bility version of the premature aging which can result in neurological disor- et al. 1993) has focused on biological hypothesis, vulnerability to alcohol- ders. As mentioned previously, pro- factors involved in protecting liver related brain damage is hastened only longed drinking with improper diet cells during metabolism; in some in people over age 50, in whom the and associated malnutrition can lead alcoholics, these protective mecha- to thiamine deficiency, a possible normal manifestations of aging al- nisms appear to be impaired. One ready have begun. This version sug- factor in KS-related brain damage. condition associated with advanced Several investigators have stressed the gests that because of the increased liver disease, including alcoholic liver vulnerability of their brains to alcohol- idea that damage in the diencephalon disease, is hepatic encephalopathy of KS patients is caused by thiamine related damage, older alcoholics will (also called portal-systemic suffer more age-related symptoms and deficiency, whereas cortical abnor- encephalopathy [PSE]). PSE is a pro- malities, most notably in the frontal impairment than their nonalcoholic gressive metabolic liver disorder that peers and younger alcoholics. lobes, are caused by alcohol neurotox- affects intellectual functioning. icity or other conditions frequently In the early observations from Alcoholics with PSE have livers so which the premature aging hypothesis associated with alcoholism (e.g., liver damaged by cirrhosis that the flow of disease or head trauma). evolved, researchers characterized the venous blood into the liver is obstruct- post mortem appearance of alcoholics’ ed, allowing toxic substances and brains as being small and shriveled Thiamine Deficiency metabolic by-products to enter the compared with the brains of age- Researchers differ in their explana- bloodstream. These toxins, which can matched nonalcoholics (Courville tions of how and why particular neu- include ammonia and manganese, 1966). The appearance was likened to ropsychological deficits are displayed circulate to the brain, where they the shrinkage that is associated with in alcoholics. One theory proposes that interfere with the actions of neuro- normal chronological aging. Other alcoholics may fall into subgroups transmitters. The effects of PSE can researchers, using neuroimaging tech- distinguished by whether their brains be reversed to some extent with liver niques, have reported comparable are vulnerable to the direct neurotoxic transplantation. findings in support of the accelerated effects of alcohol, to thiamine defi- aging hypothesis; backing the increased ciency, or to both factors (Lishman vulnerability hypothesis, older alco- OTHER INFLUENCES ON ALCOHOL- holics displayed more brain tissue loss 1990). According to this viewpoint, RELATED BRAIN INJURY in brain scans than did younger alco- alcoholics who are susceptible to alco- hol toxicity alone may develop perma- holics (see Pfefferbaum and nent or transient cognitive deficits Age Rosenbloom 1993). On the whole, associated with cortical shrinkage. most of the structural evidence sup- Those alcoholics who are susceptible When researchers first began to study ports a possible link between alco- to thiamine deficiency alone will de- the effects of alcohol on the brain, holism and premature aging. velop a mild or short-lived KS state they observed structural brain changes Unlike studies assessing brain with anterograde amnesia as a salient in alcoholics similar to those seen in atrophy, however, neuropsychological feature. Alcoholics who suffer from a nonalcoholic subjects as a result of investigations have not accumulated combination of alcohol neurotoxicity normal chronological aging. These much support for either version of the and thiamine deficiency (i.e., have observations gave rise to the “prema- premature aging hypothesis. Results dual vulnerability) will experience ture aging hypothesis.” Two versions of a few studies favor the increased widespread damage to large regions of of the hypothesis exist, each with vulnerability hypothesis, but the evi- the cerebral cortex as well as to struc- different propositions concerning the dence is inconsistent (for reviews, see tures deep within the brain. These period in an alcoholic’s life during Ellis and Oscar-Berman 1989; Evert VOL. 21, NO. 1, 1997 71
  8. 8. and Oscar-Berman 1995). In support tions common among the elderly (e.g., information. The left hemisphere usu- of the hypothesis, one study demon- chronic pain and heart disease) also ally is more efficient than the right strated that on the parts of IQ tests may increase alcohol-related problems with linguistic signals, and the right that normally pose difficulties for in this group. For example, alcohol- hemisphere is more efficient than the elderly nonalcoholic people, alco- medication interactions can have left for nonverbal signals. Scientists holics between the ages of 48 and 74 neuropsychological consequences can study differences in hemispheric performed significantly worse than ranging from drowsiness to disorien- asymmetries using procedures called same-age nonalcoholic control sub- tation; physical effects can include laterality tasks, which are sensitive to jects and younger alcoholics (Ellis hemorrhage, malnutrition, and liver left and right hemisphere functioning. 1990). The increased vulnerability damage, which also can lead to neuro- Figure 4 illustrates the neuroanatomy hypothesis leads to a second predic- psychological problems. of human laterality (for a detailed tion, however, which was not sup- description of laterality tasks, see ported by the study. Gender Oscar-Berman 1992). The second prediction hinges on Laterality tasks allow researchers the considerable evidence from a Controversy exists over whether and to conduct experiments in which con- separate line of research into possible to what extent chronic alcoholism flicting visual, auditory, or tactual right-hemisphere brain dysfunction in affects women’s brains differently stimuli are sent simultaneously to the alcoholics (see Oscar-Berman 1992). from men’s brains (Glenn 1993). two halves of the brain. These tasks Like patients with damage to the right Results of studies using the same allow researchers to measure whether techniques to measure brain structure hemisphere, alcoholics typically per- the left or the right side of the brain and function in men and women have form poorly on visuospatial tasks. copes better with the competing infor- been inconsistent. However, The similarity in performance between mation. With visual laterality tasks, researchers have found evidence of alcoholics and patients with right- the signals are presented on a computer similar degrees of brain shrinkage and hemisphere damage led researchers to screen; with auditory laterality tasks, impairment on tests of mental func- hypothesize that right-brain functions the signals are presented through stereo tioning in men and women, even are more vulnerable than left-brain earphones; and with touch tasks, the though the women participating in the functions to the effects of alcohol. Thus, stimuli are given to the right and left study had shorter drinking histories the increased vulnerability hypothesis hands. When research participants than the men (Lishman et al. 1987). predicts that older alcoholics, the Such evidence has led investigators to receive the stimuli, the side of the group in whom the effects of aging hypothesize that women’s brains may brain that is dominant for that material and alcoholism are combined, would differ from men’s brains in their sus- will favor the information coming into show deficits out of proportion to ceptibility to alcohol-related damage. the side that is contralateral, or oppo- their age on specialized tests of right- Since research suggests that alcohol site, to that hemisphere. In experi- hemisphere functioning.7 This was not may affect brain structure differently ments using auditory laterality tasks, the case in the study just described in men and women, one might also for example, researchers may present (Ellis 1990). The results of numerous expect to see gender differences in the two words (e.g., “bin” and “pin”) or other studies examining right-hemi- neuropsychological consequences of two excerpts of music simultaneously sphere functional decline in relation alcoholism. One way of studying to a subject, who then may be asked to to alcoholism and aging have not been possible neuropsychological dispari- identify the words or melodies he or sufficiently consistent to resolve the ties between male and female alco- she just heard. The left side of the premature aging issue (for a review, holics is to examine gender differences brain, which is dominant for language, see Ellis and Oscar-Berman 1989). in the functioning of the brain’s two will favor words coming into the right Regardless of alcohol’s role in hemispheres (i.e., differences in their ear, and the right half of the brain, aging, older alcoholics, by virtue of functional cerebral laterality patterns). which is dominant for music, will favor their chronological age, may be partic- This question may be important be- melodies coming into the left ear. ularly susceptible to the effects of cause structural differences in men’s Studies comparing the separate alcohol. For example, elderly alco- and women’s brains may be one factor functions of the left and right cerebral holics have an increased risk of acci- underlying gender differences in per- hemispheres have relied mainly on dents, deleterious side effects, and ceptual asymmetries and other neu- male research participants; no consis- overt toxicity resulting from alcohol ropsychological responses to alcohol. tent pattern of abnormalities in alco- intake. Treatment for medical condi- Normally, in both men and women, holics has emerged (for a review, see the left and right sides of the brain Oscar-Berman 1992). In a study that 7 Specialized tests that compare right- have disproportionate (i.e., asymmetri- included both male and female alco- hemisphere functioning with left-hemisphere functioning are called laterality tests. Laterality cal) abilities to process linguistic (e.g., holics and nonalcoholic control partic- tests are discussed in a later section; see also letters, words, and phrases) and non- ipants, however, Drake and colleagues Oscar-Berman (1992). verbal (e.g., visuospatial and musical) (1990) measured gender differences in 72 ALCOHOL HEALTH & RESEARCH WORLD
  9. 9. Brain and Behavior Impairments hemispheric asymmetries using words and music presented simultaneously in each ear (i.e., dichotic listening). The investigators found that compared with control subjects, male alcoholics were better able to identify words com- L R ing into the right ear (a left-hemisphere function) and not as able to identify melodies coming into the left ear (a right-hemisphere function). In con- trast, female alcoholics’ laterality patterns did not differ from those of control subjects on either of the di- R L R L chotic listening tasks. The authors interpreted their results to mean that male alcoholics showed evidence of right hemisphere dysfunction. Results of numerous other perceptual laterali- Olfaction Olfaction ty studies using visual, tactual, and L nostril Rnostril auditory signals have been inconsis- tent in showing abnormal asymme- Speech tries in alcoholics; these studies, Writing however, have not addressed gender differences (Oscar-Berman 1992). Continuing research on how alco- R L holism may affect the two halves of Stereognosis Stereognosis the brain differently in men and wom- R ear (i.e., tactual learning) (i.e., tactual learning) L ear en may suggest gender-specific strate- L. ear R. ear Spatial gies for treatment. construction Main language Simple language Family History center comprehension Researchers have found that adoles- Calculation Nonverbal cent and adult children of alcoholics ideation who do not drink alcohol nevertheless show deficits in neuropsychological Visual Visual functioning (for reviews, see Babor et half half al. 1994; Porjesz and Begleiter 1993). field field Evidence suggests that children of alcoholics have difficulty regulating their own behavior, organizing and R L remembering information, and learn- ing tasks that involve two- and three- Figure 4 Schematic representation of perceptual and language functions in the dimensional space. In other studies, right and left cerebral hemispheres of the human brain. abnormal brain electrical activity, measured as a reduced peak in ampli- tude in one of the electrical compo- potential alcoholism in children of planning and judgment) however, only nents of the ERP (i.e., the P300 alcoholics even before the initiation of alcoholics with a positive family histo- wave), has been observed in drinking behavior. ry of alcoholism performed poorly nondrinking sons of alcoholics who Family history of alcoholism has (Peterson et al. 1992). were performing cognitive tasks. been associated with other notable Because the electrophysiological results. In one study, intoxicated alco- abnormalities in the children of alco- holics, both with and without a family RECOVERY AND TREATMENT holics are similar to those displayed history of alcoholism, had problems on by abstinent alcoholics, researchers cognitive tests sensitive to temporal Studies suggest that slow recovery of have inferred that brain waves may lobe functions (e.g., memory). On tests cognitive functioning occurs in alco- provide an observable marker for sensitive to frontal lobe functions (e.g., holics who remain abstinent for at VOL. 21, NO. 1, 1997 73
  10. 10. least 4 weeks, and certain indicators SUMMARY AND CONCLUSIONS absence of a cure for alcohol addic- of impairment (i.e., CT and MRI tion, a detailed understanding of the images and brain glucose metabolism) Several hypotheses have been pro- biochemical actions of alcohol on have been shown to improve with posed to explain the diversity of neu- nerve cells may help in designing ropsychological abnormalities shown therapies to ameliorate its devastating prolonged abstinence (Pfefferbaum et by chronic alcoholics: (1) In patients neurological effects. s al. 1995; Volkow et al. 1994). Al- with KS, alcoholism can selectively though numerous pharmacological interfere with short-term memory, treatments have been given to alco- emotion, and other functions associat- ACKNOWLEDGMENTS holics to improve neuropsychological ed with damage to limbic system and functioning, none has proved entirely diencephalic structures; and (2) alco- The authors thank Dr. Mark Lewis successful (Martin and Nimmerrichter holics can also suffer diffuse cortical and Mr. Michael Ward for their help- 1993). Researchers have not estab- damage that affects the functioning of ful comments. lished whether recovery is complete in both brain hemispheres (e.g., abstract- most alcoholics (or what constitutes ing and problem-solving abilities, poor attention, disinhibition, and per- REFERENCES complete recovery), and they have not yet determined the typical length of severative responding). No definite BABOR, T.F.; HESSELBROCK, V.; MEYER, R.; the recovery period. 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JOIN US IN CHICAGO, NEW ORLEANS, BALTIMORE, AND INDIANAPOLIS The National Institute on Alcohol Abuse and Alcoholism (NIAAA) invites you to visit its scientific exhibit at these upcoming conferences: s American Psychological Association s American Society of Human Genetics August 15–19, 1997 October 28–November 1 Hyatt Regency Hotel Baltimore Convention Center Chicago, IL Baltimore, MD s Society for Neuroscience s American Public Health Association October 25–30, 1997 November 9–13, 1997 Morial Convention Center Indiana Convention Center New Orleans, LA Indianapolis, IN The Alcohol and Alcohol Problems Science Database (ETOH), recent NIAAA publications, and research grant information will be on display. VOL. 21, NO. 1, 1997 75

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