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Like other brain regions, the hippocampus does not operate in isolation. Information processing in the hippocampus depends on coordinated input from a variety of other structures, which gives alcohol and other drugs additional opportunities to disrupt hippocampal functioning. One brain region that is central to hippocampal functioning is a small structure in the fore brain known as the medial septum. The medial septum sends rhythmic excitatory and inhibitory signals to the hippocampus, causing rhythmic changes in the activity of hippocampal pyramidal cells. In electroencephalograph recordings, this rhythmic activity, referred to as the theta rhythm, occurs within a frequency of roughly 6 to 9 cycles per second (hertz) in actively behaving rats. The theta rhythm is thought to act as a gatekeeper, increasing or decreasing the likelihood that information entering the hippocampus from cortical structures will be processed. Information entering the hippocampus when pyramidal cells are slightly excited (slightly depolarized) has a better chance of influencing hippocampal circuitry than signals that arrive when the cells are slightly suppressed (slightly hyperpolarized).

Manipulations that disrupt the theta rhythm also disrupt the ability to perform tasks that depend on the hippocampus. Alcohol disrupts the theta rhythm in large part by suppressing the output of signals from medial septal neurons to the hippocampus. Given the powerful influence that the medial septum has on information processing in the hippocampus, the impact of alcohol on cellular activity in the medial septum is likely to play an important role in the effects of alcohol on memory. Indeed, in rats, putting alcohol directly into the medial septum alone produces memory impairments.

Other Brain Regions Involved in Alcohol-Induced Memory Impairments

The hippocampus is not the only structure involved in memory formation. A host of other brain structures also are involved in memory formation, storage, and retrieval. Recent research with humans has yielded compelling evidence that key areas of the frontal lobes play important roles in short-term memory and the formation and retrieval of long-term explicit memories. Damage to the frontal lobes leads to profound cognitive impairments, one of which is a difficulty forming new memories. Recent evidence suggests that memory processes in the frontal lobes and the hippocampus are coordinated via reciprocal connections, raising the possibility that dysfunction in one structure could have deleterious effects on the functioning of the other.

Considerable evidence suggests that chronic alcohol use damages the frontal lobes and leads to impaired performance of tasks that rely on frontal lobe functioning. "Shrinkage" in brain volume, changes in gene expression, and disruptions in how performing certain tasks affects blood flow in the brain all have been observed in the frontal lobes of alcohol-dependent subjects.

Although much is known about the effects of chronic use of alcohol on frontal lobe function, little is known about the effects of one-time use of alcohol on activity in the frontal lobes, or the relationship of such effects to alcohol-induced memory impairments. Compelling evidence indicates that acute alcohol use impairs the performance of a variety of frontal lobe-mediated tasks, like those that require planning, decisionmaking, and impulse control, but the underlying mechanisms are not known. Research also suggests that baseline blood flow to the frontal lobes increases during acute intoxication, that metabolism in the frontal lobes decreases and that alcohol reduces the amount of activity that occurs in the frontal lobes when the frontal lobes are exposed to pulses from a strong magnetic field. Although the exact meaning of these changes remains unclear, the evidence suggests that acute intoxication alters the normal functioning of the frontal lobes. Future research is needed to shed more light on this important question. In particular, research in animals will be an important supplement to studies in humans, affording a better understanding of the underlying prefrontal circuitry involved in alcohol-induced memory impairment.

Summary and Conclusions

As detailed in this brief review, alcohol can have a dramatic impact on memory. Alcohol primarily disrupts the ability to form new long-term memories; it causes less disruption of recall of previously established long-term memories or of the ability to keep new information active in short-term memory for a few seconds or more. At low doses, the impairments produced by alcohol are often subtle, though they are detectable in controlled conditions. As the amount of alcohol consumed increases, so does the magnitude of the memory impairments. Large quantities of alcohol, particularly if consumed rapidly, can produce a blackout, an interval of time for which the intoxicated person cannot recall key details of events, or even entire events. En bloc blackouts are stretches of time for which the person has no memory whatsoever. Fragmentary blackouts are episodes for which the drinker's memory is spotty, with "islands" of memory providing some insight into what transpired, and for which more recall usually is possible if the drinker is cued by others. Blackouts are much more common among social drinkers than previously assumed and should be viewed as a potential consequence of acute intoxication regardless of age or whether one is clinically dependent upon alcohol.

Tremendous progress has been made toward an understanding of the mechanisms underlying alcohol-induced memory impairments. Alcohol disrupts activity in the hippocampus via several routes - directly, through effects on hippocampal circuitry, and indirectly, by interfering with interactions between the hippocampus and other brain regions. The impact of alcohol on the frontal lobes remains poorly understood, but probably plays an important role in alcohol-induced memory impairments.

Modern neuroimaging techniques, such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), provide incredible opportunities for investigating the impact of drugs like alcohol on brain function during the performance of cognitive tasks. The use of these techniques will no doubt yield important information regarding the mechanisms underlying alcohol-induced memory impairments in the coming years. Memory formation and retrieval are highly influenced by factors such as attention and motivation. With the aid of neuroimaging techniques, researchers may be able to examine the impact of alcohol on brain activity related to these factors, and then determine how alcohol contributes to memory impairments.

Despite advances in human neuroimaging techniques, animal models remain absolutely essential in the study of mechanisms underlying alcohol-induced memory impairments. Hopefully, future work will reveal more regarding the ways in which the effects of alcohol on multiple transmitter systems interact to disrupt memory formation. Similarly, recent advances in electrophysiological recording techniques, which allow for recordings from hundreds of individual cells in several brain regions simultaneously, could provide much-needed information regarding the impact of alcohol on the interactions between disparate brain regions involved in the encoding, storage, and retrieval of information.

Tags: Memory Improvement

About the Author

NIH is the nation's medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research.