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Alcoholism and the Brain: An Overview

Marlene OscarBerman, Ph.D., and Ksenija Marinkovic, Ph.D.
Marlene OscarBerman, Ph.D., is a professor in the Departments of Anatomy and Neurobiology, Psychiatry, and Neurology, Boston
University School of Medicine, and a research career scientist at the U.S. Department of Veterans Affairs Healthcare System, Jamaica
Plain Division, Boston, Massachusetts.
Ksenija Marinkovic, Ph.D., is a research scientist at the Athinoula A. Martinos Center for Biomedical Imaging, instructor in the Radiology
Department at Harvard Medical School, and assistant in Neuroscience at the Massachusetts General Hospital, Boston, Massachusetts.
This work was supported by National Institute on Alcohol Abuse and Alcoholism grants R37AA07112, K05AA00219, K01AA13402,
and by the Medical Research Service of the U.S. Department of Veterans Affairs.
Alcoholism can affect the brain and behavior in a variety of ways, and multiple factors can influence these effects. A persons susceptibility to
alcoholismrelated brain damage may be associated with his or her age, gender, drinking history, and nutrition, as well as with the vulnerability
of specific brain regions. Investigators use a variety of methods to study alcoholismrelated brain damage, including examining brains of
deceased patients as well as neuroimaging, a technique that enables researchers to test and observe the living brain and to evaluate structural
damage in the brain. Key words: neurobehavioral theory of AODU (alcohol and other drug use); alcoholic brain syndrome; brain atrophy;
neuropsychological assessment; neurotransmission; risk factors; comorbidity; disease susceptibility; neuroimaging; treatment factors; survey of research
The brain, like most body organs, is vulnerable to injury from alcohol consumption. The risk of brain damage and related neurobehavioral deficits varies from
person to person. This article reviews the many factors that influence this risk, the techniques used to study the effects of alcoholism
1
on the brain and
behavior, and the implications of this research for treatment. (
1
Alcohol dependence, also known as alcoholism, is characterized by a craving for alcohol,
possible physical dependence on alcohol, an inability to control ones drinking on any given occasion, and an increasing tolerance to alcohols effects
[American Psychiatric Association (APA) 1994].)
About half of the nearly 20 million alcoholics in the United States seem to be free of cognitive impairments. In the remaining half, however,
neuropsychological difficulties can range from mild to severe. For example, up to 2 million alcoholics develop permanent and debilitating conditions that
require lifetime custodial care (Rourke and Lberg 1996). Examples of such conditions include alcoholinduced persisting amnesic disorder (also called
WernickeKorsakoff syndrome) and dementia, which seriously affects many mental functions in addition to memory (e.g., language, reasoning, and
problemsolving abilities) (Rourke and Lberg 1996). Most alcoholics with neuropsychological impairments show at least some improvement in brain
structure and functioning within a year of abstinence, but some people take much longer (Bates et al. 2002; Gansler et al. 2000; Sullivan et al. 2000).
Unfortunately, little is known about the rate and extent to which people recover specific structural and functional processes after they stop drinking.
However, research has helped define the various factors that influence a persons risk for experiencing alcoholismrelated brain deficits, as the following
sections describe.
RISK FACTORS AND COMORBID CONDITIONS THAT INFLUENCE ALCOHOLRELATED BRAIN DAMAGE
Alcoholisms effects on the brain are diverse and are influenced by a wide range of variables (Parsons 1996). These include the amount of alcohol
consumed, the age at which the person began drinking, and the duration of drinking; the patients age, level of education, gender, genetic background, and
family history of alcoholism; and neuropsychiatric risk factors such as alcohol exposure before birth and general health status. Overall physical and mental
health is an important factor because comorbid medical, neurological, and psychiatric conditions can interact to aggravate alcoholisms effects on the brain
and behavior. Examples of common comorbid conditions include:
Medical conditions such as malnutrition and diseases of the liver and the cardiovascular system
Neurological conditions such as head injury, inflammation of the brain (i.e., encephalopathy), and fetal alcohol syndrome (or fetal alcohol
effects)
Psychiatric conditions such as depression, anxiety, posttraumatic stress disorder, schizophrenia, and the use of other drugs (Petrakis et al.
2002).
These conditions also can contribute to further drinking.
MODELS FOR EXPLAINING ALCOHOLRELATED BRAIN DAMAGE
Some of the previously mentioned factors that are thought to influence how alcoholism affects the brain and behavior have been developed into specific
models or hypotheses to explain the variability in alcoholismrelated brain deficits. The accompanying table lists the prevailing models (OscarBerman
2000). It should be noted that the models that focus on individual characteristics cannot be totally separated from models that emphasize affected brain
systems because all of these factors are interrelated. Several of the models have been evaluated using specialized tests that enable researchers to make
inferences about the type and extent of brain abnormalities.
Hypotheses Proposed to Explain the Consequences of Alcoholism for the Brain
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Hypotheses Emphasizing the Personal Characteristics Associated With Vulnerability
Characteristic Hypothesis
Aging Premature aging hypothesis: Alcoholism accelerates aging. Brains of alcoholics resemble brains of
chronologically old nonalcoholics. This may occur at the onset of problem drinking (accelerated aging)
or later in life when brains are more vulnerable (increased vulnerability or cumulative effects).
Gender Alcoholism affects women more than men. Although women and men metabolize alcohol differently, it is
not yet clear if womens brains are more vulnerable than mens brains to the effects of alcoholism.
Family history Alcoholism runs in families; thus, children of alcoholics face increased risk of alcoholism and associated
brain changes.
Vitamin deficiency Thiamine deficiency can contribute to damage deep within the brain, leading to severe cognitive deficits.
Hypotheses Emphasizing the Vulnerability of Brain Regions or Systems
Region/System Hypothesis
Entire brain Vulnerable to cerebral atrophy.
Limbic system, thalamus, and
hypothalamus
Vulnerable to alcoholinduced persisting amnesic disorder (also known as WernickeKorsakoff
syndrome).
Frontal lobe systems More vulnerable to the effects of alcoholism than other brain regions/systems.
Right hemisphere More vulnerable to the effects of alcoholism than the left hemisphere.*
Neurotransmitter systems (e.g., gamma
aminobutyric acid [GABA], glutamate,
dopamine, acetylcholine, and serotonin
systems)
Several neurotransmitter systems are vulnerable to effects of alcoholism.
*The right hemisphere is also believed to be more vulnerable to the effects of normal aging than the left hemisphere, which is taken as support for the
premature aging hypothesis listed above.
NOTE: These hypotheses are not mutually exclusive; some are interrelated. Supporting data for these models come from neurobehavioral and
electrophysiological studies, brain scans, and post mortem neuropathology.
Models Based on Characteristics of Individual Alcoholics
Premature Aging Hypothesis. According to this hypothesis, alcoholism accelerates natural chronological aging, beginning with the onset of problem
drinking.
An alternate version suggests that older patients (age 50 and older) are especially susceptible to the cumulative effects of alcoholism, and aging is
accelerated only later in life. The preponderance of scientific evidence suggests that although alcoholismrelated brain changes may mimic some of the
changes seen in older people, alcoholism does not cause premature aging. Rather, the effects of alcoholism are disproportionately expressed in older
alcoholics (OscarBerman 2000).
Gender. Although it has been hypothesized that womens brain functioning is more vulnerable to alcoholism than mens, studies of gender differences have
not consistently found this to be true (see Wuethrich 2001 for a review), even though women and men metabolize alcohol differently (i.e., women achieve
higher blood alcohol contents [BACs] than men after consuming the same amount of alcohol). However, it is not known whether this comparison between
men and women holds among older populations (OscarBerman 2000).
Family History. Family history of alcoholism has been found to be important because it can influence such things as tolerance for alcohol and the amount
of consumption needed to feel alcohols effects. Also, studies examining brain functioning in people with and without a positive family history of alcoholism
have shown that there are clear differences between the groups on measures of brain electrical activity (Porjesz and Begleiter 1998).
Vitamin Deficiency. Research on malnutrition, a common consequence of poor dietary habits in some alcoholics, indicates that thiamine deficiency
(vitamin B
1
) can contribute to damage deep within the brain, leading to severe cognitive deficits (OscarBerman 2000). The exact location of the affected
parts of the brain and underlying neuropathological mechanisms are still being researched (see the next section).
Models Based on Vulnerable Brain Systems
The outer, convoluted layer of brain tissue, called the cerebral cortex or the gray matter, controls most complex mental activities (see figure 1). Just beneath
it are the nerve fibers, called the white matter, that connect different cortical regions and link cortical cells with other structures deep inside the brain
(subcortical regions).
Figure 1 Schematic drawing of the human brain, showing regions
vulnerable to alcoholismrelated abnormalities.
Areas of the brain that are especially vulnerable to alcoholismrelated damage are the cerebral cortex and subcortical areas such as the limbic system
(important for feeling and expressing emotions), the thalamus (important for communication within the brain), the hypothalamus (which releases hormones in
response to stress and other stimuli and is involved in basic behavioral and physiological functions), and the basal forebrain (the lower area of the front part
of the brain, involved in learning and memory) (OscarBerman 2000). Another brain structure that has recently been implicated is the cerebellum (Sullivan
2000), situated at the base of the brain, which plays a role in posture and motor coordination and in learning simple tasks.
AlcoholRelated Brain Atrophy. According to one hypothesis, shrinkage (i.e., atrophy) of the cerebral cortex and white matter, as well as possible
atrophy of basal forebrain regions, may result from the neurotoxic effects of alcohol (Lishman 1990). Furthermore, thiamine deficiency may result in damage
to portions of the hypothalamus (perhaps because blood vessels break in that region). According to this hypothesis, alcoholics who are susceptible to
alcohol toxicity
2
may develop permanent or transient cognitive deficits associated with brain shrinkage. (
2
Some people may have better immunity than
others to alcohols toxic effects.) Those who are susceptible to thiamine deficiency will develop a mild or transient amnesic disorder, with shortterm
memory loss as the salient feature. Patients with dual vulnerability, those with a combination of alcohol neurotoxicity and thiamine deficiency, will have
widespread damage to large regions of the brain, including structures deep within the brain such as the limbic system. These people will exhibit severe
shortterm memory loss and collateral cognitive impairments (OscarBerman 2000).
Frontal Lobe Vulnerability. Although alcoholics have diffuse damage in the cerebral cortex of both hemispheres of the brain, neuropathological studies
performed on the brains of deceased patients as well as findings derived from neuroimaging studies of living brains point to increased susceptibility of frontal
brain systems to alcoholismrelated damage (Moselhy et al. 2001; OscarBerman 2000; Sullivan 2000). The frontal lobes are connected with all other lobes
of the brain (i.e., the parietal, temporal, and occipital lobes on both halves of the brain; see figure 1), and they receive and send fibers to numerous
subcortical structures. Behavioral neuroscientists have determined that the anterior region of the frontal lobes (i.e., the prefrontal cortex) is important for
engaging in ordinary cognitive, emotional, and interpersonal activities. The prefrontal cortex is considered the brains executivethat is, it is necessary for
planning and regulating behavior, inhibiting the occurrence of unnecessary or unwanted behaviors, and supporting adaptive executive control skills such as
goaldirected behaviors, good judgment, and problemsolving abilities. Disruptions of the normal inhibitory functions of prefrontal networks often have the
interesting effect of releasing previously inhibited behaviors. As a result, a person may behave impulsively and inappropriately, which may contribute to
excessive drinking.
There is evidence that the frontal lobes are particularly vulnerable to alcoholismrelated damage, and the brain changes in these areas are most prominent
as alcoholics age (OscarBerman 2000; Pfefferbaum et al. 1997; Sullivan 2000) (see figure 2). Other studies of frontal lobe function in older alcoholics have
confirmed reports of a correlation between impaired neuropsychological performance (e.g., executive control skills, as noted above) and decreased blood
flow or metabolism (energy use) in the frontal lobes, as seen using neuroimaging techniques (Adams et al. 1998).
Figure 2 Brain MRI scans of ageequivalent men with different histories of alcohol use. The image
shows clear evidence of brain shrinkage in the alcoholic compared with the control subject. The graph
on the right shows that older alcoholics have less cortical tissue than younger alcoholics, and that the
prefrontal cortex is especially vulnerable to alcohols effects. The location of the temporal, parietal, and
occipital regions of the brain can be seen in figure 1.
*Zscore is a mathematical measure that is useful for showing the difference between the recorded
value and a normal value.
SOURCE: Pfefferbaum et al. 1997.
Vulnerability of the Right Hemisphere. Some investigators have hypothesized that functions controlled by the brains right hemisphere are more
vulnerable to alcoholismrelated damage than those carried out by the left hemisphere (see OscarBerman and Schendan 2000 for review). Each
hemisphere of the human brain is important for mediating different functions. The left hemisphere has a dominant role in communication and in
understanding the spoken and written word. The right hemisphere is mainly involved in coordinating interactions with the threedimensional world (e.g.,
spatial cognition).
Differences between the two cerebral hemispheres can easily be seen in patients with damage to one hemisphere but not the other (from stroke, trauma, or
tumor). Patients with left hemispheric damage often have problems with language; patients with right hemispheric damage often have difficulty with maps,
designs, music, and other nonlinguistic materials, and they may show emotional apathy.
Alcoholics may seem emotionally flat (i.e., they are less reactive to emotionally charged situations), and may have difficulty with the same kinds of tasks
that patients with damage to the right hemisphere have difficulty with. New research has shown that alcoholics are impaired in emotional processing, such
as interpreting nonverbal emotional cues and recognizing facial expressions of emotion (Kornreich et al. 2002; Monnot et al. 2002; OscarBerman 2000).
Yet, despite the fact that emotional functioning can be similar in some alcoholics and people with right hemisphere damage, research provides only
equivocal support for the hypothesis that alcoholism affects the functioning of the right hemisphere more than the left (OscarBerman and Schendan 2000).
Impairments in emotional functioning that affect alcoholics may reflect abnormalities in other brain regions which also influence emotional processing, such
as the limbic system and the frontal lobes.
Disruption of Neurotransmitter Systems. Brain cells (i.e., neurons) communicate using specific chemicals called neurotransmitters. Neuronal
communication takes place at the synapse, where cells make contact. Specialized synaptic receptors on the surface of neurons are sensitive to specific
neurotransmitters. Alcohol can change the activity of neurotransmitters and cause neurons to respond (excitation) or to interfere with responding (inhibition)
(Weiss and Porrino 2002), and different amounts of alcohol can affect the functioning of different neurotransmitters. Over periods of days and weeks,
receptors adjust to chemical and environmental circumstances, such as the changes that occur with chronic alcohol consumption, and imbalances in the
action of neurotransmitters can result in seizures, sedation, depression, agitation, and other mood and behavior disorders.
The major excitatory neurotransmitter in the human brain is the amino acid glutamate. Small amounts of alcohol have been shown to interfere with
glutamate action. This interference could affect several brain functions, including memory, and it may account for the shortlived condition referred to as
alcoholic blackout. Chronic alcohol consumption increases glutamate receptor sites in the hippocampus, an area in the limbic system that is crucial to
memory and often involved in epileptic seizures. During alcohol withdrawal, glutamate receptors that have adapted to the longterm presence of alcohol may
become overactive, and this overactivity has been repeatedly linked to neuronal death, which is manifested by conditions such as stroke and seizures.
Deficiencies of thiamine caused by malnutrition may contribute to this potentially destructive overactivity (Crews 2000).
Gammaaminobutyric acid (GABA) is the major inhibitory neurotransmitter. Available evidence suggests that alcohol
3
initially potentiates GABAs effects
(i.e., it increases inhibition, and often the brain becomes mildly sedated). (
3
The amount of alcohol needed to cause this effect depends on the person.)
However, over time, prolonged, excessive alcohol consumption reduces the number of GABA receptors. When the person stops drinking, decreased
inhibition combined with a deficiency of GABA receptors may contribute to overexcitation throughout the brain. This in turn can contribute to withdrawal
seizures within a day or two. It should be noted that the balance between the inhibitory action of GABA and the excitatory action of glutamate is a major
determinant of the level of activity in certain regions of the brain; the effects of GABA and glutamate on withdrawal and brain function are probably interactive
(see Valenzuela 1997 for review).
Alcohol directly stimulates release of the neurotransmitter serotonin, which is important in emotional expression, and of the endorphins, natural substances
related to opioids, which may contribute to the high of intoxication and the craving to drink. Alcohol also leads to increases in the release of dopamine
(DA), a neurotransmitter that plays a role in motivation and in the rewarding effects of alcohol (Weiss and Porrino 2002). Changes in other neurotransmitters
such as acetylcholine have been less consistently defined. Future research should help to clarify the importance of many neurochemical effects of alcohol
consumption. Furthermore, areas amenable to pharmacological treatment could be identified by studying regionally specific brain neurochemistry in vivo
using neuroimaging methods such as positron emission tomography (PET) and single photon emission computerized tomography (SPECT) (described
below). New information from neuroimaging studies could link cellular changes directly to brain consequences observed clinically. In the absence of a cure
for alcoholism, a detailed understanding of the actions of alcohol on nerve cells may help in designing effective therapies.
TECHNIQUES FOR STUDYING ALCOHOLRELATED BRAIN DAMAGE
Researchers use multiple methods to understand the etiologies and mechanisms of brain damage across subgroups of alcoholics. Behavioral neuroscience
offers excellent techniques for sensitively assessing distinct cognitive and emotional functionsfor example, the measures of brain laterality (e.g., spatial
cognition) and frontal system integrity (e.g., executive control skills) mentioned earlier. Followup post mortem examinations of brains of wellstudied
alcoholic patients offer clues about the locus and extent of pathology and about neurotransmitter abnormalities. Neuroimaging techniques provide a window
on the active brain and a glimpse at regions with structural damage.
Behavioral Neuroscience
Behavioral neuroscience studies the relationship between the brain and its functionsfor example, how the brain controls executive functions and spatial
cognition in healthy people, and how diseases like alcoholism can alter the normal course of events. This is accomplished by using specialized tests
designed expressly to measure the functions of interest. Among the tests used by scientists to determine the effects of alcoholism on executive functions
controlled by the frontal lobes are those that measure problemsolving abilities, reasoning, and the ability to inhibit responses that are irrelevant or
inappropriate (Moselhy et al. 2001; OscarBerman 2000). Tests to measure spatial cognition controlled by the right hemisphere include those that measure
skills important for recognizing faces, as well as those that rely on skills required for reading maps and negotiating two and threedimensional space
(visuospatial tasks) (OscarBerman and Schendan 2000). With the advent of sophisticated neuroimaging techniques (described below), scientists can even
observe the brain while people perform many tasks sensitive to the workings of certain areas of the brain.
Neuropathology
Researchers have gained important insights into the anatomical effects of longterm alcohol use from studying the brains of deceased alcoholic patients.
These studies have documented alcoholismrelated atrophy throughout the brain and particularly in the frontal lobes (Harper 1998). Post mortem studies will
continue to help researchers understand the basic mechanisms of alcoholinduced brain damage and regionally specific effects of alcohol at the cellular
level.
Neuroimaging
Remarkable developments in neuroimaging techniques have made it possible to study anatomical, functional, and biochemical changes in the brain that are
caused by chronic alcohol use. Because of their precision and versatility, these techniques are invaluable for studying the extent and the dynamics of brain
damage induced by heavy drinking. Because a patients brain can be scanned on repeated occasions, clinicians and researchers are able to track a
persons improvement with abstinence and deterioration with continued abuse. Furthermore, brain changes can be correlated with neuropsychological and
behavioral measures taken at the same time. Brain imaging can aid in identifying factors unique to the individual which affect that persons susceptibility to
the effects of heavy drinking and risk for developing dependence, as well as factors that contribute to treatment efficacy.
Imaging of Brain Structure. With neuroimaging techniques such as computerized tomography (CT) and magnetic resonance imaging (MRI), which allow
brain structures to be viewed inside the skull, researchers can study brain anatomy in living patients. CT scans rely on xray beams passing through
different types of tissue in the body at different angles. Pictures of the inner structure of the brain are based on computerized reconstruction of the paths
and relative strength of the xray beams. CT scans of alcoholics have revealed diffuse atrophy of brain tissue, with the frontal lobes showing the earliest and
most extensive shrinkage (Cala and Mastaglia 1981).
MRI techniques have greatly influenced the field of brain imaging because they allow noninvasive measurement of both the anatomy (using structural MRI)
and the functioning (using functional magnetic resonance imaging [fMRI], described below) of the brain with great precision. Structural MRI scans are based
on the observation that the protons derived from hydrogen atoms, which are richly represented in the body because of its high water content, can be aligned
by a magnetic field like small compass needles. When pulses are emitted at a particular frequency, the protons briefly switch their alignment and relax
back into their original state at slightly different times in different types of tissue. The signals they emit are detected by the scanner and converted into
highly precise images of the tissue. MRI methods have confirmed and extended findings from post mortem and CT scan studiesnamely, that chronic use
of alcohol results in brain shrinkage. This shrinkage is most marked in the frontal regions and especially in older alcoholics (OscarBerman 2000;
Pfefferbaum et al. 1997; Sullivan 2000). Other brain regions, including portions of the limbic system and the cerebellum, also are vulnerable to shrinkage.
Imaging of Brain Function: Hemodynamic Methods. Hemodynamic methods create images by tracking changes in blood flow, blood volume, blood
oxygenation, and energy metabolism that occur in the brain in response to neural activity. PET and SPECT are used to map increased energy consumption
by the specific brain regions that are engaged as a patient performs a task. One example of this mapping involves glucose, the main energy source for the
brain. When a dose of a radioactively labeled glucose (a form of glucose that is absorbed normally but cannot be fully metabolized, thus remaining trapped
in a cell) is injected into the bloodstream of a patient performing a memory task, those brain areas that accumulate more glucose will be implicated in
memory functions. Indeed, PET and SPECT studies have confirmed and extended earlier findings that the prefrontal regions are particularly susceptible to
decreased metabolism in alcoholic patients (Berglund 1981; Gilman et al. 1990). It is important to keep in mind, however, that frontal brain systems are
connected to other regions of the brain, and frontal abnormalities may therefore reflect pathology elsewhere (Moselhy et al. 2001).
Even though using low doses of radioactive substances that decay quickly minimizes the risks of radiation exposure, newer and safer methods have
emerged, such as MRI methods. MRI is noninvasive, involves no radioactive risks, and provides both anatomical and functional information with high
precision. The fMRI method is sensitive to metabolic changes in the parts of the brain that are activated during a particular task. A local increase in
metabolic rate results in an increased delivery of blood and increased oxygenation of the region participating in a task. The blood oxygenation level
dependent (BOLD) effect is the basis of the fMRI signal. Like PET and SPECT, fMRI permits observing the brain in action, as a person performs cognitive
tasks or experiences emotions.
In addition to obtaining structural and functional information about the brain, MRI methodology has been used for other specialized investigations of the
effects of alcohol on the brain. For example, structural MRI can clearly delineate gray matter from white matter but cannot detect damage to individual nerve
fibers forming the white matter. By tracking the diffusion of water molecules along neuronal fibers, an MRI technique known as diffusion tensor imaging (DTI)
can provide information about orientations and integrity of nerve pathways, confirming earlier findings from post mortem studies which suggested that heavy
drinking disrupts the microstructure of nerve fibers. Moreover, the findings correlate with behavioral tests of attention and memory (Pfefferbaum et al. 2000).
These nerve pathways are critically important because thoughts and goaloriented behavior depend on the concerted activity of many brain areas.
Another type of MRI application, magnetic resonance spectroscopy imaging (MRSI), provides information about the neurochemistry of the living brain. MRSI
can evaluate neuronal health and degeneration and can detect the presence and distribution of alcohol, certain metabolites, and neurotransmitters.
Imaging of Brain Function: Electromagnetic Methods. In spite of their excellent spatial resolutionthat is, the ability to show precisely where the
activation changes are occurring in the brainhemodynamic methods such as PET, SPECT, and fMRI have limitations in showing the time sequence of
these changes. Activation maps can reveal brain areas involved in a particular task, but they cannot show exactly when these areas made their respective
contributions. This is because they measure hemodynamic changes (blood flow and oxygenation), indicating the neuronal activation only indirectly and with
a lag of more than a second. Yet, it is important to understand the order and timing of thoughts, feelings, and behaviors, as well as the contributions of
different brain areas.
The only methods capable of online detection of the electrical currents in neuronal activity are electromagnetic methods such electroencephalography
(EEG), eventrelated brain potentials (ERP),
4
and magnetoencephalography (MEG). (
4
The ERP method is considered derived from
electroencephalography.) EEG reflects electrical activity measured by small electrodes attached to the scalp. Eventrelated potentials are obtained by
averaging EEG voltage changes that are timelocked to the presentation of a stimulus such as a tone, image, or word. MEG uses sensors in a machine
that resembles a large hair dryer to measure magnetic fields generated by brain electrical activity. These techniques are harmless and give us insight into
the dynamic momenttomoment changes in electrical activity of the brain. They show when the critical changes are occurring, but their spatial resolution is
ambiguous and limited.
ERP and MEG have confirmed that alcohol exerts deleterious effects on multiple levels of the nervous system. These effects include impairment of the
lowerlevel brain stem functions resulting in behavioral symptoms such as dizziness, involuntary eye movement (i.e., nystagmus), and insecure gait, as well
as impairment of higher order functioning such as problem solving, memory, and emotion. ERP and MEG are remarkably sensitive to many alcoholrelated
phenomena and can detect changes in the brain that are associated with alcoholism, withdrawal, and abstinence. That is, these methods show different
activity patterns between healthy and alcoholdependent individuals, those in withdrawal, and those with a positive family history of alcoholism. As shown in
figure 3, when brain electrical activity is measured in response to target stimuli (which require the subject to respond in some way) and nontarget stimuli (to
be ignored by the subject), the brains of alcoholics are less responsive than the brains of nonalcoholic control subjects. Some of the ERP abnormalities
observed in alcoholics do not change with abstinence, and similar abnormalities have been reported in patients who do not drink but come from families with
a history of alcoholism. The possibility that such abnormalities may be genetic markers for the predisposition for alcoholism is under intensive scrutiny in
studies combining genetic and electromagnetic measures in people with or without a family history of alcoholism (Porjesz and Begleiter 1998).
Figure 3 Brain electrical activity measured as eventrelated potentials
(ERPs) in response to target stimuli (which require the subject to respond in
some way) and nontarget stimuli (to be ignored by the subject). The brains of
alcoholics are less responsive than the brains of nonalcoholic control
subjects. The heights of the peaks are measured in terms of the strength of
the electrical signal (volts) recorded from the scalp over time (in thousandths
of a second, or mS).
SOURCE: Porjesz and Begleiter 1995.
IMPLICATIONS FOR TREATMENT
Because alcoholism is associated with diverse changes to the brain and behavior, clinicians must consider a variety of treatment methods to promote
cessation of drinking and recovery of impaired functioning. With an optimal combination of neuropsychological observations and structural and functional
brain imaging results, treatment professionals may be able to develop a number of predictors of abstinence and relapse outcomes, with the purpose of
tailoring treatment methods to each individual patient. Neuroimaging methods have already provided significant insight into the nature of brain damage
caused by heavy alcohol use, and the integration of results from different methods of neuroimaging will spur further advances in the diagnosis and treatment
of alcoholismrelated damage. Clinicians also can use brain imaging techniques to monitor the course of treatment because these techniques can reveal
structural, functional, and biochemical changes in living patients across time as a result of abstinence, therapeutic interventions, withdrawal, or relapse. For
example, functional imaging studies might be used to evaluate the effectiveness of drugs such as naltrexone on withdrawalinduced craving. (Naltrexone is
an anticraving medicine that suppresses GABA activity.) Additionally, neuroimaging research already has shown that abstinence of less than a month can
result in an increase in cerebral metabolism, particularly in the frontal lobes, and that continued abstinence can lead to at least partial reversal in loss of
brain tissue (Sullivan 2000). Neuroimaging indicators also can be useful in prognosis, permitting identification and timely treatment of patients at high risk for
relapse.
SUMMARY
Alcoholics are not all alike; they experience different subsets of symptoms, and the disease has different origins for different people. Therefore, to
understand the effects of alcoholism, it is important to consider the influence of a wide range of variables. Researchers have not yet found conclusive
evidence for the idea that any one variable can consistently and completely account for the brain deficits found in alcoholics. The most plausible conclusion
is that neurobehavioral deficits in some alcoholics result from the combination of prolonged ingestion of alcohol, which impairs the way the brain normally
works, and individual vulnerability to some forms of brain damage. Characterizing what makes alcoholics vulnerable remains the subject of active research.
In the search for answers, it is necessary to use as many kinds of tools as possible, keeping in mind that specific deficits may be observed only with
certain methods, specific paradigms, and particular types of people with distinct risk factors. Neuroscience provides sensitive techniques for assessing
changes in mental abilities and observing brain structure and function over time. When techniques are combined, it will be possible to identify the pattern,
timing, and distribution of the brain regions and behaviors most affected by alcohol use and abuse. Electromagnetic methods (ERP and MEG) specify the
timing of alcoholinduced abnormalities, but the underlying neural substrate (i.e., the anatomical distribution of the participating brain areas) cannot be
unequivocally evaluated based on these methods alone. Conversely, the hemodynamic methods (fMRI, PET, and SPECT) have good spatial resolution but
offer little information about the sequence of events. Drawing on the respective advantages of these complementary methods, an integrated multimodal
approach can reveal where in the brain the critical changes are occurring, as well as the timing and sequence in which they happen (Dale and Halgren
2001). Such confluence of information can provide evidence linking structural damage, functional alterations, and the specific behavioral and
neuropsychological effects of alcoholism. These measures also can determine the degree to which abstinence and treatment result in the reversal of atrophy
and dysfunction.
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Prepared: July 2004

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