Alcoholism and Human Electrophysiology : Part 3

by National Institute of Health

(Page 3 of 5)

P300 (P3a, P3b)

Most studies investigating electrophysiological deficits in alcoholics have focused on the P300 or P3 component. The P3 is a large positive component that occurs between 300 and 700 ms after a "significant" stimulus and is not related to the physical features of the stimulus (brightness and shape for visual stimuli, or loudness and pitch for auditory stimuli). A stimulus can be "significant" by being relevant to a task (the subject must press a button whenever a specific stimulus, such as a blue triangle, occurs), by having a motivating influence (the subject wins money after responding to the stimulus correctly), or by occurring rarely or unpredictably. The P3 is thought to reflect aspects of working memory, the temporary storage of information required for complex cognitive tasks such as learning, reasoning, and comprehension. Specifically, P3 may reflect attention allocation and updating processes. P3 also is thought to reflect cognitive closure, or the termination of a mental process, which involves inhibition over widespread cortical areas. The amplitude of P3 reflects inhibition of responses to irrelevant stimuli that the subject must ignore in order to respond effectively to the relevant targets. The timing of P3 occurrence (latency) reflects mental processing speed; the earlier and larger the P3, the easier the processing.

The ERP task most commonly used to elicit the P3 is the so-called "oddball" task, in which rare "oddball" stimuli are embedded in a series of frequent stimuli (standards or nontargets). For example, in an auditory task, the subject listens to frequent "boops" and rare "beeps" in a random stream of tone bursts. If the subject is asked to attend or respond to the rare "beep" stimulus, it is designated as a target; the P3s recorded in response to these task-relevant targets are largest posteriorly on the scalp (over the parietal region) and are designated as P3b components. If the subject is not asked to attend to rare "beep" stimuli, P3s recorded to these unattended rare nontarget stimuli in a repetitive background have a more frontal distribution and are designated as P3a; although rare nontargets elicit these P3as, frequent nontargets usually do not elicit any P3s.

Studies over the last few decades have found that the amplitudes of P3s to task-relevant target stimuli (P3b) are significantly lower in abstinent alcoholics than in nonalcoholics. This deficit in alcoholics occurs with both auditory and visual tasks but is seen more consistently with visual tasks. More recent studies have indicated that low P3 amplitudes are present not only in male alcoholics but also in female alcoholics, though not to the same extent as in males. Figure 2A illustrates reduced P3 amplitudes in alcoholics, compared with control subjects, in response to target stimuli in a visual paradigm.

Not only do alcoholics manifest low amplitude P3b components in response to target stimuli, they also manifest low P3a components in response to rare nontargets in both visual and auditory modalities. Recent reports have indicated that alcoholics manifest reduced P3 amplitudes to both Go (target) and No-Go stimuli. Furthermore, alcoholics manifest less differentiation between their responses to target and nontarget stimuli. In keeping with various neurophysiological explanations of the P3 component, the amplitude of P3 is thought to reflect CNS inhibition (the larger the P3, the greater the inhibition). An increase in theta power, an inhibitory rhythm, underlies P3 (see the following section on event-related oscillations). Most information a person is exposed to is irrelevant and must be suppressed while the person selectively responds to the relevant information; this accounts for the large amplitude of the P3. The low-amplitude P3 components manifested by alcoholics indicate that they have less CNS inhibition than control subjects. Researchers have hypothesized that this lack of inhibition, or underlying CNS disinhibition (hyperexcitability), is involved in a predisposition to alcoholism.

As expected, nonalcoholics manifest their largest P3b amplitudes in response to targets over parietal regions of the scalp, and their largest P3a amplitudes in response to rare nontargets. However, alcoholics manifest similar low-amplitude P3s across all areas of the scalp in response to rare target and nontarget stimuli.

Despite P3's maximal amplitude over parietal areas in response to targets when scalp electrodes are used, studies with electrodes inserted into the brain (depth electrodes) in humans indicate that P3s originate in the frontal cortex; the hippocampus, which is important in the consolidation of new memories; and the amygdala, a part of the limbic system involved in producing and controlling emotional behavior. Recent functional magnetic resonance (fMRI) studies support these findings and implicate another part of the limbic system, the anterior cingulate area of the frontal cortex, as critical for P3 generation. The lower amplitude P3 components, along with the weaker and less well organized sources in alcoholics, suggest disorganized and inefficient brain functioning. This global neurophysiological pattern suggests cortical disinhibition, providing further support for underlying CNS hyperexcitability in alcoholics.

Event-Related Oscillations (EROS)

The neural oscillations that underlie ERPs are called EROs. Although EROs are measured in the same frequency bands as spontaneous resting EEGs - namely, delta (1-3 Hz), theta, alpha, beta, and gamma - functionally they are different from spontaneous resting EEG rhythms. EROs temporally are related to the sensory and cognitive processing of stimuli. During sensory reception, groups of neurons that are close together fire together at fast rates in the gamma range. Cognitive processing (attention to an auditory rather than a visual stimulus), however, involves communication between brain regions that are somewhat farther apart. This processing involves synchronization between the brain regions in the alpha and beta frequency ranges. Higher cognitive processing (working memory, determining if a stimulus has been seen before) involves interactions between widely separated brain regions (frontal and parietal lobes). Higher cognitive processing involves slow synchronization in the theta or delta frequency range. Thus, faster frequencies represent synchronization of groups of neurons in more local areas, whereas slower frequencies are involved in synchronization over longer distances in the brain.

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