Elsevier

Biological Psychiatry

Volume 45, Issue 4, 15 February 1999, Pages 494-507
Biological Psychiatry

Original Articles
Event-related potential index of semantic mnemonic dysfunction in abstinent alcoholics

https://doi.org/10.1016/S0006-3223(98)00062-6Get rights and content

Abstract

Background: The objective of the study was to expand the investigation of the match/mismatch mnemonic impairment in the semantic domain in sober alcoholics.

Methods: Event-related potentials (ERPs) were recorded from 28 healthy adults and 36 sober alcoholics in a category (either animals or fruits/vegetables) match/nonmatch S1–S2 paradigm.

Results: There was a significant interaction of ERP amplitude (c3) between groups (controls vs. alcoholics) and stimulus conditions (category match vs. nonmatch) at the posterior brain regions; the c3 component was smaller for the category match than for nonmatch trials in controls, with the absence of such c3 differences in alcoholics. There were no significant ERP differences between the two groups in processing the sample stimuli. The ERPs (c2) elicited by the animal category were larger than those for the vegetable category in both groups. The alcoholics showed prominent suppressed activation of left temporo-occipital brain regions under both matching and nonmatching conditions, as demonstrated by the current source density maps. The alcoholics were also slower and less accurate than the controls in judging both category matching and nonmatching stimuli, while neither of the two groups demonstrated shorter response times to the matching stimuli.

Conclusions: These data suggest that alcoholics are less efficient in the semantic mnemonic match/nonmatch process, and are less likely to be deteriorated in the stage of forming the template for such match/nonmatch comparisons.

Introduction

Alcohol dependence and abuse affects approximately 13% of the adult American population (American Psychiatric Association 1987). Compared to the deleterious effect of alcohol on the various organ systems (liver, peripheral nervous system, etc.), where the pathological processes are relatively clear, the underlying mechanisms of the psychoactive effects of alcohol are poorly understood; however, the neuropsychological literature does reveal a wide range of cognitive deficits associated with alcohol dependence, including impairment in perceptual–motor skills, visual–spatial functions, learning, memory, and abstraction and problem solving Parsons and Nixon 1993, Glenn et al 1994, Porjesz and Begleiter 1996, Braun and Richer 1993. Among these deficits, the alcohol-related memory problems have received special attention (Oscar-Berman 1990). This is not only due to the existence of Wernicke–Korsakoff’s syndrome, whose distinguishing symptoms are memory problems Glass and Butters 1985, Jacobson et al 1990, Pollux et al 1995, but also because mnemonic difficulties might be especially sensitive indicators of alcoholism-related cognitive impairment (Ryan and Butters 1986). In sober alcoholics who failed to meet criteria of organic mental syndromes, the cognitive impairments have been more diverse, generalized, and subtle, and up to half of sober alcoholics often failed to manifest any apparent impairments with the usual neuropsychological measures Parsons 1986, Parsons and Nixon 1993.

The assessment and evaluation of subtle memory dysfunction in sober alcoholics requires appropriate methods. The typical tests to assess mnemonic aspects in nonhuman primates have been forced-choice tests of recognition, either the delayed nonmatching-to-sample (DNMS) or the delayed matching-to-sample (DMS) Oscar-Berman 1990, Zola-Morgan and Squire 1985, Zhou and Fuster 1996, Webster et al 1995. The basic steps of DNMS/DMS are: a sample stimulus (S1) is presented to an animal; after some delay, the animal is exposed to the test stimulus (S2, which is either identical to S1 or is novel) and gets rewarded upon its correct choice of the nonmatching or matching stimulus. It is reported that human subjects have a strong bias to match in comparison to monkeys’ spontaneous preference for novelty in these forced-choice recognition tests (Aggleton et al 1988). The DMS has thus been widely accepted to test anterograde amnesia, visual short-term memory, and other mnemonic processing in human subjects Holdstock et al 1995, Lange et al 1995, Swearer and Kane 1996.

Event-related potentials (ERPs) are neuroelectric indices shown to be sensitive to various aspects of alcohol use, such as alcohol intoxication, tolerance, and withdrawal (Porjesz and Begleiter 1987). A cluster of ERP components (P3, N400, N2, N1) have been found to be aberrant in sober alcoholics Realmuto et al 1993, Frank et al 1994, Porjesz and Begleiter 1995, Cohen et al 1995. These aberrations are associated with certain information processing deficits that are involved in the various operations of ERP paradigms, such as oddball tasks for the P300, semantic processing paradigm for the N400, and discrimination tasks for the N2. It is interesting that, despite the different cognitive emphasis involved in each ERP paradigm, rudimentary template match–mismatch memory processes are somehow shared by these ERP paradigms (Porjesz and Begleiter 1996). To distinguish deviant stimuli from repetitive background stimuli, or to discriminate stimuli on the basis of semantic congruity/incongruity, a template needs to be formed for comparison. The ERP aberrations of the alcoholics (reduced P3 amplitude, prolonged N2 latency) indicate that they have less efficient match/mismatch processes than controls; it has been speculated that either the template is not formed or retained or that the match/mismatch processes themselves are impaired (Porjesz and Begleiter 1996).

In a modified DMS task using visual line fragment stimuli that were difficult to name, Begleiter et al (1993) detected an ERP component peaking around 247 msec that differentiates recognized from unrecognized stimuli; it is termed the visual memory potential (VMP). In previous studies in our laboratory, similar VMPs were elicited in DMS tasks by nonsense lines (Begleiter et al 1993), faces and face scrambles (Hertz et al 1994), familiar and unfamiliar faces (Begleiter et al 1995), and concrete object pictures (Zhang et al 1995). In these tasks, the VMP occurs at almost the same peak latency; higher voltages are obtained to the nonmatching S2 compared to the matching S2, and the strongest sources are over occipitotemporal regions in healthy adults. This temporal and spatial pattern of the VMP in combination with its cognitive features resembles the functional role of inferior temporal (IT) neurons of monkeys, which has been hypothesized to compare the representations of current visual stimuli with the internal representations of remembered stimuli (Eskandar et al 1992). In particular, the VMP proved to be sensitive to a subset of processes that contribute to the visual mnemonic comparison between the trace held in short-term memory and the current input stimuli. Not surprisingly, the VMP was significantly increased to novel, unfamiliar stimuli compared to previously observed, familiar stimuli in controls but not in alcoholics, suggesting visual memory aberrance in alcoholics (Porjesz and Begleiter 1996). Unlike the oddball tasks, where neither ERP waveforms elicited to novel stimuli nor frequent stimuli could index the neural representation of the template for comparison, the VMP was found to be involved in the encoding processes of the sample (Ji et al in press), which actually serves as the template in matching-to-sample processes. Therefore, the VMP could be an appropriate tool to test the aforementioned speculation proposed by BP and HB on the impaired match/mismatch processes in alcoholics, i.e., whether the alcoholics have problems in forming the template and/or they are simply impaired in match/mismatch processes per se. This study attempts to further investigate the match/mismatch mnemonic impairment in sober alcoholics by additional examination of the ERP elicited by the template sample in DMS tasks.

Evidence from a series of studies conducted in our laboratory also demonstrated that the VMP could reflect differences between the processing of object pictures with and without verbal labels Hertz et al 1994, Begleiter et al 1995, Zhang et al 1995. To elaborate the semantic sensitive feature possessed by the VMP, this study employed a paradigm similar to those delayed matching-to-sample tasks where the VMP was elicited in healthy subjects, with one modification. Rather than judging whether the S1 and S2 are matched on physical identity, subjects judged whether sequentially presented pairs of stimuli were in the same superordinate category. This modification requires subjects to use information other than that available in the surface features of the pictures; that is, they must respond with the superordinate labels. For example, when pictures of cow and cat are presented sequentially, instead of responding to the visual features (recognizing the picture as “cow” and “cat”), responding at the superordinate label (categorizing the two pictures as “animals”) is required. We hypothesized that the semantic information was extracted explicitly to make correct judgments for this experiment. By investigating the effect of semantic information on the VMP, we are able to examine mnemonic processes that were semantically mediated, which has been found to be impaired in abstinent alcoholics (Porjesz and Begleiter 1996).

Section snippets

Subjects

There were 64 adults in this study. The experimental subjects (male:female = 27:9, n = 36, mean age = 36.8 years, SD ± 6.7 years) were recruited from the Addictive Disease Hospital of Kings County Hospital Center and were diagnosed as alcohol dependent without concomitant diagnosis of alcohol-induced organic mental disorders (DSM-III-R). Over the past 6 months, 7 alcoholics claimed to be abstinent from alcohol; the remaining 29 subjects had 17.4 ± 13.7 (4–60) drinks per day (a drink is a 12-oz.

Results

The alcoholic group consisted of 27 men (36.5 ± 6.9 years old) and 9 women (37.3 ± 6.2 years old); there was no significant difference [F(1,34) = 0.09, p = .77] between the group mean age of male and female subjects. The control group consisted of 17 men (25.8 ± 4.4 years old) and 11 women (24.2 ± 3.5 years old); there also was no significant difference [F(1,26) = 1.00, p = .33] between the group mean age of male and female subjects; however, there was a significant age difference [F(1,60) =

Discussion

Neither in processing the sample stimuli (S1) as a whole, nor in processing the two different samples (animal S1 and vegetable S1) respectively, do alcoholics manifest any significant differences from controls. Both groups demonstrate larger ERPs (mainly the c2 component) response to the animal sample compared to the vegetable sample to the same extent (no interaction of group × stimulus condition). Since encoding/extracting information from the sample stimulus enables the forming of the

Acknowledgements

Supported by NIH grants AA05524 and AA02686.

The authors wish to thank Arthur Stimus, David Chorlian, Brian Beckrich, Sergio Valentini, Elisabeth Iskander, Vladimir Kotlyarevsky, and Howard L. Cohen for their valuable assistance.

References (46)

  • B.W Patterson et al.

    Alcoholism and family history of alcoholismEffects on visual and auditory event-related potentials

    Alcohol

    (1987)
  • A Pfefferbaum et al.

    Late event-related potential changes in alcoholics

    Alcohol

    (1987)
  • P.M Pollux et al.

    Random generation deficit in alcoholic Korsakoff patients

    Neuropsychologia

    (1995)
  • G Realmuto et al.

    Event-related potential evidence of dysfunction in automatic processing in abstinent alcoholics

    Biol Psychiatry

    (1993)
  • M.J Wright et al.

    Event related potentials during covert orientation of visual attentionEffects of cue validity and directionality

    Biol Psychology

    (1995)
  • X.L Zhang et al.

    Event related potentials during object recognition tasks

    Brain Res Bull

    (1995)
  • American Electroencephalographic Society guidelines for standard electrode position nomenclature

    J Clin Neurophysiol

    (1991)
  • H Begleiter et al.

    Neuroradiological and neurophysiological evidence of brain deficits in chronic alcoholics

    Acta Psychiatr Scand

    (1980)
  • C.M Braun et al.

    A comparison of functional indexes, derived from screening tests, of chronic alcoholic neurotoxicity in the cerebral cortex, retina and peripheral nervous system

    J Stud Alcohol

    (1993)
  • F Cadaveira et al.

    Multimodality exploration of event-related potentials in chronic alcoholics

    Alcohol Clin Exp Res

    (1991)
  • H.L Cohen et al.

    Auditory P300 in young alcoholicsRegional response characteristics

    Alcohol Clin Exp Res

    (1995)
  • D Deacon et al.

    Variation in the latencies and amplitudes of N400 and NA as a function of semantic priming

    Psychophysiology

    (1995)
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