Alcohol and the Cerebellum

Effects on Balance, Motor Coordination, and Cognition

EDITH V. SULLIVAN, PH.D., MARGARET J. ROSENBLOOM, M.A.,

ANJALI DESHMUKH, M.D., JOHN E. DESMOND, PH.D., AND ADOLF PFEFFERBAUM, M.D.

Alcoholics often suffer from motor incoordination resulting from alcohol­related cerebellar

damage. However, the effect of cerebellar structural damage on cognitive functioning has not

been clearly demonstrated. It is not known if the relationships observed between cerebellar

damage and functional impairments persist with abstinence from alcohol. Cell death may cause

permanent loss of function, whereas tissue shrinkage without permanent cell loss might

represent the potential for recovery. This article examines research on the interrelationship of

alcohol­related abnormalities in cerebellar structure and function. Research such as this may

provide knowledge to guide future rehabilitation efforts. KEYWORDS: AODE (alcohol and other drug

effects); cerebellum; motor coordination; cognitive process; equilibrium; brain atrophy; AOD impairment

In addition to its role in controlling it contains about as many nerve cells (ap­ ne of the most widely recog­ movement, the cerebellum may play an proximately 5 billion for each structure) nized signs of acute alcohol important role in the acquisition of motor (Ghez 1991). The cerebellum consists of intoxication is staggering gait. skills and the cognitive processes that con­ several subdivisions, each controlling or The motor incoordination trol movement (Ito 1993). The cerebellum element of intoxication is routinely as­ facilitating different behavioral functions. sessed by highway patrol officers when also may help augment cognitive processes The cerebellum includes the left and right they use standard tests of stance imbal­ originating in the cerebrum (Leiner et al. hemispheres and the vermis (figure 1). O 1993), such as language production ance (otherwise known as gait ataxia) and Unlike the cerebrum, where each hemi­ eye­hand incoordination. (Appollonio et al. 1993; Petersen 1993) and sphere controls the opposite side of the The obvious signs of gait and coordi­ mental imagery (Ryding et al. 1993). The body, in the cerebellum each hemisphere nation disturbance demonstrated by these role of the cerebellum in cognition is com­ controls movement on the same side of the simple tests usually resolve once the plex and controversial. body. Thus, damage to the left hemisphere This article reviews current knowledge person has become sober. However, disrupts movement of the left arm or leg, 1 careful study of alcoholics reveals resid­ on the motor and cognitive processes con­ whereas damage to the right hemisphere trolled or facilitated by the cerebellum and ual, subtle, persistent deficits in balance disrupts movement of the right limbs. describes damage to the cerebellum associ­ that may put them at increased risk of The vermis lies between and in front of ated with long­term alcoholism. The article accidents, such as falling. These deficits the cerebellar hemispheres. It has 10 lobules then explains how researchers are seeking may be related to alcohol­induced patho­ and is named for its wormlike appearance. logical changes in the cerebellum, one of to relate this damage both to problems with balance and motor coordination and to Damage to the vermis can result in poor the brain’s main centers of postural con­ control of posture and upright position, trol and motor coordination. some of the characteristic cognitive deficits associated with alcoholism. ataxia (widespread stance and unsteady 1 balance), and dysarthria (irregular and The exact definition of the term “alcoholism” varies explosive cadence of speech). The superior with the article cited. Readers are encouraged to (upper) lobules of the vermis are especially consult the original source for the precise definition. TRUCTURE OF THE EREBELLUM S C In general, however, alcoholism may be defined as involved with refinement of coordination abnormal craving for alcohol accompanied by certain The term cerebellum comes from the Latin and postural stability of the legs and trunk. behavioral manifestations including loss of control and means “little brain.” Although it is only The more inferior (lower) lobules support over alcohol consumption. about one­tenth the weight of the cerebrum, coordinated movement of the arms.

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OGNITIVE UNCTIONS cerebrum. These functions include certain ume also declines with age in nonalcoholics. C F OF THE CEREBELLUM aspects of verbal learning (Bracke­Tolkmitt In contrast to alcohol, which exerts its greatest effect on the anterior superior et al. 1989; Canavan et al. 1994) as well as lobules, normal aging affects mostly the Nerve cells in the cerebellum communicate word production (Petersen et al. 1989), posterior lobules (Raz et al. 1992). Vermal with nerve cells in the cerebrum, brain problem­solving (Kim et al. 1994), and shrinkage appears to be related to daily stem, and spinal cord, including regions planning (Grafman et al. 1992). alcohol consumption but not necessarily to involved in cognitive functions, such as spatial and other sensory perception, age in alcoholics (Karhunen et al. 1994). problem­solving, organization, and plan­ LCOHOL S FFECTS ON A ’ E ning. Skilled performance of motor tasks CEREBELLAR STRUCTURE involves timing, feedback from visual and LCOHOL S FFECTS ON A ’ E sensory cues, coordination, and learned Cerebellar degeneration is common in CEREBELLAR FUNCTION patterns or dynamics of movement that alcoholics (Torvik and Torp 1986; Victor allow movements to be made quickly, and Laureno 1978). Researchers have Postural and Motor Function smoothly, and relatively effortlessly (Gil­ looked at cerebellar damage in the brains of The demonstration that increasing doses man et al. 1981). These functions include alcoholics during postmortem examination. of alcohol are associated with increasing both motor and cognitive processes. The The most consistently reported structural severity of an impairment would provide cerebellum also participates in certain damage in the cerebellum of alcoholics is important evidence that the impairment is aspects of motor skill learning (Sanes et tissue volume loss in the anterior superior alcohol related. However, this type of al. 1990), control of reflexive actions (e.g., vermis (Victor et al. 1989). Tissue volume alcohol dose­response relationship has blinking one’s eye in response to a signal loss in this area is due especially to either been difficult to demonstrate for cerebellar associated with the delivery of a puff of air shrinkage or atrophy of Purkinje cells impairment. In one study (Estrin 1987), to the eye) (McGlinchy­Berroth et al. (Charness 1993; Victor et al. 1989; Pentney degree of ataxia was shown not to be as­ 1994), motor ideation (e.g., the mental 1993), large nerve cells that make up much sociated with total lifetime consumption representation of a movement) (Ryding et of the volume of the vermis. of alcohol; however, degree of eye­foot al. 1993), and tactile learning of complex Structures at the base of the cerebellum incoordination was related to increasing figures (Roland et al. 1989). also may be affected by excessive alcohol alcohol consumption when ataxic alco­ The cerebellum may contribute to cogni­ consumption (Allsop and Turner 1966; holics were pooled with nonataxic alco­ tive functions carried out primarily by the Victor et al. 1989). These regions regulate holics and healthy control subjects. eye movements, particularly when both the Signs of ataxia can wax and wane

DITH ULLIVAN H head and the eyes are in motion. Damage to E V. S , P .D., is an associate corresponding with periods of alcoholic professor in the Department of Psychiatry these regions can cause “slippage” of the drinking and abstinence, providing evi­ visual image (i.e., apparent displacement of and Behavioral Sciences, Stanford Univer­ dence for specific adverse effects of sity School of Medicine, Stanford, CA, and a visually perceived object) and result in alcohol on motor coordination. Abstinent visual illusions and postural instability, a health science specialist in the Psychiatry alcoholics may show improvement in Service, Veterans Affairs (VA) Palo Alto which may be precursors of falling balance (Allsop and Turner 1966; Diener (Radebaugh et al. 1985). In addition, such Health Care System, Palo Alto, California. et al. 1984; Victor et al. 1989) and periph­ visual misperception can result in errors of eral nerve functioning, including percep­

MARGARET J. ROSENBLOOM, M.A., is a eye­hand or eye­foot coordination, such as tion of touch and position sense, that is, is needed for safe driving. health science specialist in the Psy­ the ability to detect the position of the chiatry Service, VA Palo Alto Health Cerebellar volume loss is confirmed by body and its parts (Palliyath and Schwartz neuroimaging techniques that provide Care System. 1993). New research must be conducted quantitative measurement of the different to determine if alcohol­related imbalance

NJALI ESHMUKH tissue types of the brain. Studies using A D , M.D., is a postdoctor­ results from cerebellar pathology or from al fellow in the Psychiatry Service, VA computed tomography and magnetic reso­ poor functioning of the peripheral nervous 2 nance imaging (MRI) (Haubek and Lee Palo Alto Health Care System. system in the body’s extremities, such as 1979; Hillbom et al. 1986; Kennedy et al. the hands and feet. Peripheral neuropathy

OHN ESMOND H 1976) have shown that cerebellar atrophy, J E. D , P .D., is a research (i.e., the deadening of feeling in the hands fellow in the Department of Radiology, shrinkage, or both can occur in the absence and feet) can occur in alcoholics, resulting Stanford University. of clinical signs such as ataxia or clinically in decreased sensation that may lead to detectable cognitive impairment. imbalance. It is unknown whether im­

ADOLF PFEFFERBAUM, M.D., is a profes­ Cerebellar shrinkage is most notable in provement in motor function results from sor in the Department of Psychiatry and older alcoholics with at least a 10­year improvement in the condition of the Behavioral Sciences, Stanford University cerebellum or from the use of new per­ duration of alcoholism (Victor et al. 1989). School of Medicine, and director of psychi­ formance strategies dependent on intact Whether the degree of cerebellar shrinkage atry research in the Psychiatry Service, VA brain regions. is related to the quantity of alcohol con­ Palo Alto Health Care System. sumed is unknown. Cerebellar tissue vol­ In one study (Diener et al. 1984), alcoholics with clinically detectable atax­ 2 Supported by National Institute on Computerized tomography and magnetic resonance ia of stance and gait were tested twice:

Alcohol Abuse and Alcoholism grant imaging provide slicelike structural images of the once after several hours of detoxification

AA–05965 and the Department of brain, the former using X rays and the latter using and again about a year and a half after the

Veterans Affairs. radio waves within a powerful magnetic field. initial examination. At the second testing,

VOL. 19, NO. 2, 1995 139 An MRI study identified significant cerebellar shrinkage in detoxified patients with chronic alcoholism (Davila et al. 1994). These researchers found that older alcohol- ics, ages 40 to 63 years, who were free of clinically detectable Korsakoff’s syndrome, had a deficit in balance and significant cerebellar shrinkage involving the hemi- spheres and vermis. These alcoholics were administered an extensive battery of tests that assessed cognitive and sensory as well as motor functioning. The test results re- vealed mild deficits in problem-solving, ability to sequence and organize informa- tion, and visuospatial capacity but did not reveal any detectable deficit in explicit memory (i.e., ability to remember new information after intervals of interference from irrelevant material) (Shear et al. 1994b; Sullivan et al. 1995). However, the subjects’ balance, as a group, was notably impaired, even though these alcoholics were tested after being abstinent from alcohol for about 1 month (Davila et al. 1994). The degree of vermal shrinkage in these patients was related to the extent of ataxia when some members of the group had remained Based on these findings, it appears that a balance was guided visually but did not abstinent from alcohol, whereas the rest genetic predisposition to alcoholism may relate to scores on the cognitive tests. Thus, had resumed drinking. Relative to initial dampen neuronal receptor sensitivity to cerebellar shrinkage alone could not account testing, the abstainers showed marked alcohol and reduce alcohol’s behavioral for these alcohol-related cognitive defects. improvement in postural stability, whereas effects. These relationships also may ac- the relapsers showed significant increase count for the reduced untoward effect that in measures of ataxia. alcohol consumption has on motor control CONCLUSION A functional neuroimaging study used in alcoholics with positive family histories positron emission tomography (PET) to of alcoholism, compared with those who do The combined disorders of balance and study the ability of the brain regions to not have family histories of alcoholism. visuospatial ability put alcoholics at incorporate glucose, the brain’s primary Neuroimaging might help clarify the increased risk of falls and other accidents. energy source. This study revealed that relationship between cerebellar structural This may be especially true of older alcoholic patients with ataxia showed and functional changes during abstinence. alcoholics (Cherpitel 1992; Malmivaara et hypometabolism (lower than expected A similar approach has been applied to the al. 1993). Such accidents may arise from glucose uptake by the brain) in the superior cerebrum, where researchers have used incoordination between the visual and cerebellar vermis, whereas alcoholics motor systems and from poor adaptation neuroimaging techniques to track the pro- without ataxia did not show cerebellar to changes in sensory and motor input gression and recovery of volume loss hypometabolism (Gilman et al. 1990). resulting from alcohol-related cerebellar during periods of active drinking and absti- These results provide compelling evidence damage. However, a correlation between that alcohol-related ataxia is attributable nence (Shear et al. 1994a; Pfefferbaum in cerebellar structural damage and the specifically to cerebellar dysfunction. press). However, quantitative neuroimaging cognitive functions of the cerebellum has Genetics also may play a role in studies have not yet been reported on the not been clearly demonstrated. alcohol-related motor deficits. Using PET, cerebellum in recovering alcoholics. The reversibility of cerebellar structural Volkow and colleagues (1995) examined changes is not known, and it is not known the link between genetic predisposition to Cognitive Function if the relationships observed between cere- alcoholism and reduced sensitivity to alco- bellar damage and functional impairments hol in the brain. The researchers studied the Alcoholics often exhibit cognitive deficits persist with abstinence. To the extent that effect of a drug that mimics alcohol (lora- in visuospatial processing and problem- the structural change represents cell death, zepam) and which is believed to activate solving (reviewed in Parsons et al. 1987). it may be permanent, and function may not receptors in the brain that are sensitive to These cognitive abilities, controlled pri- recover. Tissue shrinkage without perma- alcohol. Nonalcoholic subjects with family marily by the frontal and parietal lobes of nent cell loss may account for variance in histories of alcoholism showed blunted the cerebrum, also may be compromised the correlation between cerebellar structural metabolism of lorazepam in the cerebellum by damage to the cerebellar hemispheres. and functional impairment and might and smaller adverse effects on motor per- To date, however, no studies have defi- represent the potential for recovery. Future formance relative to nonalcoholic subjects nitely attributed cognitive dysfunction to investigations will need to focus on the without family histories of alcoholism. cerebellar volume loss in alcoholics. reversibility and interrelationship of

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