Vol. 15, No.4 July/August 199 1

0145-6oO8/9I/ 1504-0607$3.00/0 ALCOHOLISM: CLINICAL

AND

EXPERIMENTAL RESEARCH

Multimodality Exploration of Event-Related Potentials in Chronic Alcoholics Fernando Cadaveira, Cartes Grau, Margarita Roso, and Miquel Sanchez-Turet

Short- and long-latency auditory evoked potentials (SAEPs and LAEPs), visual-evoked potentials (VEPs), and contingent negative variation (CNV) were studied in 32 chronic alcoholics and their age-, sex-, and education-matched control subjects. The alcoholics exhibited a delayed SAEP peak V and an increase in the Ill-V and IV intervals, increasedVEP PlOO latency, increased LAEP N2 and P3 latencies and increased LAEP N1-P2 amplitude. The analysis of the anomalies at a clinical level indicates a differential sensitivity of the event-related potentials. The parameters most sensitive to chronic alcohol consumption were (in descending order) P3 latency, peak V latency, the I-V and I l l 4 intervals, and PlOO latency. Key Words: Alcoholism, Event-relatedPotentials, Multimodality.

HE CHRONIC consumption of alcohol leads to alterT ations in the central nervous system, though many patients do not show any other clinical signs than those proper to the alcoholism, especially if they are young or in the initial stages of the illness. Even in patients who are clinically only slightly affected, structural and functional alterations can be detected by neuroradiological',2 and neuropsych~logical~*~ methods. Measurement of event-related potentials (ERPs) allows noninvasive examination of the functional integrity of various neural systems in normal and neurologically or psychically diseased subjects. In the case of alcoholics, this technique has proved valuable for evaluation of the integrity of various stages of information processing (for a review see Porjesz and Begleiter'~~ and Williams7). Up to now, however, most studies of ERPs in alcoholics have each examined only one potential and since the subject groups have varied from study to study in age, sex, severity of the illness, etc, it is difficult to relate the data for different ERPs so as to obtain an integrated picture of the functional effects of alcoholism. In our work, we have examined a group of chronic alcoholic patients by means of a neurophysiological battery comprising visual evoked potentials (VEPs), contingent negative variation (CNV), and short- and long-latency From the Department of Psychiatry and Clinical Psychobiology, Universitat de3arcelona (C.G., M.R., MS-T.); and the Department of Clinical Psychology and Psychobiology, University of Santiago de Compos&a, Coruria, Spain. Received for publication March 2, 1990; accepted January 16, 1991. This work was partially supported by a Foment0 de Investigacion CientiJica e Tecnica grant from the Xunta de Galicia. Reprint requests: Fernando Cadaveira, Departamento de Psicoloxia Clinica e Psicobioloxia, Universidadede Santiago de Compostela, Campus Universitario,15702 Santiago de Compostela, Coruiia, Spain. Copyright 0 1991 by The Research Society on Alcoholism. Alcohol Clin Exp Res, Vol 15, No 4, 1991: pp 607-61 1

auditory evoked potentials (SAEPs and LAEPs), the latter by means of a paradigm that enables the P3 component to be measured. By simultaneous evaluation of various types of ERP, we pursue two general objectives: first to describe and analyze the characteristics of the ERP waveforms in alcoholics and second to examine the differential sensitivity of each test for the detection of clinical anomalies in these patients. The multimodal examination also permits the description at a clinical level of the alterations that each patient has in the different ERPs. METHOD Subjects We examined 32 patients diagnosed as chronic alcoholics according to the criteria of the DSM-HI, and 32 healthy volunteer controls matched with the alcoholics by sex, age, and education. The mean age of the patients was 38.6 years (SD = 9.4, minimum 23 years, maximum 57 years) and each had a history of alcoholism going back at least 8 years (mean = 19.1, maximum 30 years). At the time of examination, they had been abstinent for between 25 and 35 days and had not had any medication in the previous 72 hr. The control group subjects were abstemious or sporadic drinkers (under 20 gm alcohol/day) of mean age 39.9 years (SD = 9.3, minimum 22 years, maximum 55 years). Neither patients nor controls had history of head trauma, coma, anoxia-ischaemia, cardiovascular,hepatic, or respiratory disease, psychiatric disorders, or other addictions (except tobacco).

EEG Recording Stimulation and amplification, filtering, averaging, and graphical analysis of the EEG signal were camed out using a SICAN neurophysiologicalrecording apparatus. Electroencephalographic(EEG) activity was recorded using pure tin electrodes, positioned in an elastic cap according to the 10-20 system (Electrocap, Inc). Electroocular (EOG) activity was recorded using Ag/AgCl cup electrodes in sub- and supraorbitallocations. The contaminated trials were eliminated from further analysis for automatic artifact rejection. Impedance remained under 5 kohms during all sessions.

SAEPs Ipsilateral and contralateral SAEP records were obtained simultaneously by using reference electrodes located on both mastoids and an active electrode at the vertex. The ground electrode was placed on the forehead. Potentials were evoked by monaural auditory stimuli consisting of clicks of alternate polarity with a duration of 100 psec, an intensity of 110 dBpeSPL, and a stimulation frequency of 10 Hz.The EEG signal was amplified 100,000 times and filtered with a bandpass of 200 to 3000 Hz (12 dB/octave). Each potential was obtained from the average of 2000 responses for a 10-msec period. 607

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VEPs VEPs were recorded using active electrodes at 01 and 02, a reference electrode at Cz, and a forehead ground electrode. Stimulation consisted of a black and white checkerboard pattern, presented for 500 msec to both eyes, that inverted the position of the black and white checks with a frequency of 1 Hz. The checkerboard was displayed on a CRT monitor placed 50 cm from the patient's eyes, where each square subtended an angle of 30 min. The EEG activity was amplified 20,000 times and filtered with a bandpass of 0.5 to 100 Hz. Each potential was obtained from the average of 100 responses of 250 msec.

CNV data for the alcoholic and control groups were subiected to oneway ANOVA. In all cases, the Bonferroniprocedure was used to correct the significance level of the F values. To evalute differences among the ERPs regarding their sensitivity to chronic alcohol consumption, we calculated, for each ERP, the percentage of patients with anomalous values of some parameter for that ERP, and compared the percentages using a x2 test. ERP parameters were deemed pathological if more than 2.5 control group SD from the control group mean. Association among different anomalies was evaluated in the alcoholic group by calculating a Pearson correlation matrix for those variables for which the patients differed significantly from the controls.

LAEPs and P3

To obtain both LAEPs and P3, an oddball paradigm was used in which ERPs were elicited by binaural 1,000 Hz tones with an amplitude of 70 or 90 dBpeSPL. The stimuli were randomly intermixed in series in which the louder tones, more frequent (80%), were the standard stimulation, and the sofier tones, less frequent (20%), were the target stimulation. The subjects had to count the soft tones. Active electrodes were located at Cz and Pz, the reference was the signal from linked electrodes placed on both mastoids, and the ground was on the forehead. Signals were amplified 20,000 times and filtered with a bandpass of 0.5 to 50 Hz. Each record was obtained from the average of 32 target-evoked responses of 820 msec. CNV CNV was obtained by a reaction time paradigm with a previous warning signal; the interstimulus interval was 2 sec, and the interval between successive tests, 15 sec. The warning stimulus (Sl) was a flash and the imperative stimulus (S2), a sound emitted by a loudspeaker placed behind the subject, who had to respond as quickly as possible by pressing a key with his dominant hand. EEG activity was recorded using an active electrode placed at the vertex, linked mastoid electrodes as reference and a forehead ground. The signal was amplified 20,000 times and filtered through a lowpass filter of 50 Hz cutoff, with a time-constant of 10 sec. The 2 sec prior to S1 were used to establish the baseline. For each subject, 15 valid 10-sec responses were averaged. Procedure To effect the neurophysiological tests, the subjects were seated in a comfortable armchair in a sound-attenuated and dim-lighted room (14 foot-candles). To avoid the possible influence of circadian variations, all recording sessions took place between 11:30 AM and 14:30 PM. Audiometry performed before the sessions confirmed that the subjects had hearing thresholds lower than 50 dBpeSPL. SAEPs, LAEPs and P3, VEPs, and CNV were recorded in that order. At least two records were obtained for each ERP modality. All records were stored on diskettes for subsequent analysis. Data Analysis ERP components were identified by computer program without regard to subject diagnosis. Thirty-three parameters were extracted for each subject: 12 for SAEPs (the latencies of peaks I, 111, and V and the interpeak intervals 1-111, 111-V, and I-V for both ears); 2 for VEPs (the latency of PlOO for scalp locations 01 and 02); 14 for LAEPs (the latencies of the N 1, p2, N2, and p3 components and the Pak-to-Wd amplitudes of the N1-P2, P2-N2, and N2-P3 complexes for locations Cz and Pz); and 5 for CNV (the inter-stimulus interval was divided into five 400msec segments and the average amplitude of each above the prestimulus baseline was calculated). Statistical analysis was performed using the SPSS software package. Data for SAEP, VEP, and LAEP parameters and P3 were subjected to two-way ANOVA, SAEPs for group (alcoholics or controls) X ear (left or right) and VEPs, LAEPS,and P3 for group x electrode placement.

RESULTS

Effects of Chronic Alcohol Consumption of ERPs Table 1 shows the results of two-way ANOVA of the SAEP, VEP, LAEP, and P3 values for each ear or lead of alcoholics and controls. After a month of abstinence, the alcoholic group SAEP values were significantly greater than those of the control group for the peak V latency ( p < 0.01) and for the interpeak intervals 111-V ( p < 0.0 1) and I-V ( p < 0.0 1). A lengthening of the latency of the PlOO component is also found in the VEPs ( p < 0.0 1). For the LAEPs and the P3 component, the alcoholics present a significant increase in the N1-P2 amplitude ( p < 0.01) and an elongation in the N2 and P3 latencies ( p < 0.01). The LAEP peak-topeak amplitudes were all greater for Cz than Pz leads, significantly so for P1-N1 ( p < 0.01), N1-P2 ( p < 0.05) and N2-P3 ( p < 0.05). SAEP parameters were unaffected by ear, and no parameters were significantly affected by interactions between the effects of group and ear or lead. One-way ANOVA of CNV data did not show any statistically significant differences between alcoholics and controls, although the average amplitude of all five segments analyzed was lower for the alcoholic group. In Fig. 1 the SAEP, VEP, and LAEP plots of three alcoholic patients are compared with those of a control of the same age. It shows, at an individual level, some of the anomalies described for the group as a whole. Differential Sensitivity of the ERP Parameters to Chronic Alcohol Consumption The ERP parameters differed considerably regarding the number of alcoholics with pathological values (Table 2). The most sensitive parameters were P3 latency (pathological in 15 patients); peak V latency (1 3), the I-V (1 2), and 111-V ( 1 1) intervals, PlOO latency (9), and the N1-P2 amplitude (5). In all, SAEP parameters were pathological in 18 patients, VEP parameters in 9, LAEP parameters in 17, and CNV in 1. The various potentials differed regarding the number of patients with pathological waveforms ( X 2 = 16.78 for 3 df;p < 0.00 1). Intersubject Differences The multimodal analysis performed I33ealed diffelWNXs among the patients regarding the ERP alterations suffered.

MULTIMODALITY EXPLORATION OF ERPs IN ALCOHOLICS

609

Table 1. F Values Given by Two-way ANOVA of SAEPs (Group x Ear) and of VEPs and LAEPs (Group x Lead) of Abstinent Chronic Alcoholics and Their Controls

SAEPs (n = 32) Latencies I Ill V Intervals 1-111

Ill-v

I-v

Group (G)

Ear (E)

GxE

0.05 1.13 61.61**

1.61 0.28 0.59

0.13 0.09 0.92

0.71 43.14" 50.65"

1.09 1.31 0.02

0.18 1.31 0.51

Lead (01,02)

Lead (Cz,Pz)

GxL

VEPs PI 00

45.67"

LAEPs Latencies P1 N1 P2 N2 P3 Amplitudes P1-N1 N1-P2 P2-N2 N2-P3

p < 0.05; ** p

1-

0.19

0.07 1.30 0.36 14.89" 78.85"

0.88 2.08 3.21 2.30 2.56

0.00 11.55" 3.07 0.01

23.35" 10.85' 7.03 9.24'

0.02 0.01 0.02

0.37 0.21 0.87 1.53 0.12 1.02

-=0.01, as corrected by the Bonferroni procedure.

%yV w & p3

I11

P

I

I I

p2

I

+

+

I

ZXdL L I-v

I

I

-

] .2

uv

'u

8

0.06

*

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] 10 uv

I

I

I

I u

1 *qJ-& I

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I

& 0 5 lo

' *

*

I

1

I

I

I

0

125

1 250

I 0

I

20

I

400

I

600

1

8oo.I.cc

Fig. 1. SAEPs, VEPs, LAEPs, and P3 of three abstinent chronic alcoholics and a control of the same age. Besides some anomalies described for the sample group as a whole, different abnormalities in the ERPs can be detected in each of the three patients. (3 variables exceeding the mean of the control group by 2.5 SD or more.

For three patients, only visual potentials were pathological, for five, only brainstem potentials, and for seven, only LAEPs and P3; both visual and brainstem potentials were pathological for two patients, both visual and P3 for one, and both brainstem and P3 for five; P3 and visual and brainstem potentials were all pathological for two patients, and all four ERP signals were pathological for one patient. Finally, there are four patients that do not present any alteration in ERPs. Pearson correlation analysis failed to reveal significant associations among the various potentials.

DISCUSSION

Event-Related Potentials in Abstinent Chronic Alcoholics Few studies of ERPs in alcoholics have been carried out, and agreement among different reports has depended on the potential studied. Our results coincide with those of most authors in showing increases in the SAEP 111-V and I-V intervals'-" and a significant delay in peak V.*,'* A lengthened VEP PlOO latency wave in response to flash stimuli has been reported both in alcoholics showing clinical signs of visual a l t e r a t i ~ n ' ~and , ' ~ in those that do not have such signs.'' The response to a checkerboard

610

CADAVEIRA ET AL.

Table 2. Numbers (N)and Percentages (YO) of Alcoholics with Pathological SAEP, VEP, LAEP, and CNV Parameters (Values 2.5 so Higher Than Control Group Mean)

N

(W

3 2 13 2 11 12 14

(9.37) (6.25) (40.62) (6.25) (34.37) (37.50) (56.25) (43.75)

VEPs P100 No alterations

9 23

(28.13) (71.87)

IAEPs N2 P3 PI-N1 Nl-P2 Alteration in some parameter No alterations

2 15 1 5 17 15

(6.25) (46.87) (3.12) (15.62) (53.13) (46.87)

1 1

(3.12) (3.12) (3.12) (96.88)

SAEPs I 111 V 1-111 Ill-v I-v Alteration in some parameter No alterations

CNV CNV2 CNV3 Alteration in some parameter No alterations

18

1

31

alcoholic patients. Augmentation/reduction studies and our own recent finding of increased amplitudes among middle-latency auditory evoked potentials3 further suggest that N1-P2 amplitude is also a reflection of deficient modulation of sensorial input in these patients. Like Skerchok and C ~ h e and n ~ Van ~ den B o s ~ hwe ,~~ found alcoholics to have lower CNV amplitudes than controls, though in our work the differences were not statistically significant probably because we used a central electrode; Skerchok and Cohen and Van den Bosch found greater CNV depression for frontal electrodes. This decrease in CNV amplitude may reflect attentional deterioration in alcoholic patients, perhaps as a result of deficiencies in the central inhibition system^.^^,^^

Diflerential Sensitivity of the ERP Parameters to Chronic Alcohol Consumption Recording several different ERPs for the same group of subjects allowed comparison among the ERPs regarding their sensitivity to chronic alcohol consumption. Taking the normality criterion chosen (M f 2.5 SD) SAEP parameters were pathological in 56% of the patients, VEPs in 28%, LAEPs in 53%, and CNV in 3% (Table 2). Since the different potentials reflect the activity of different functional systems, the present results support the notion that alcohol has different effects on different levels of information processing in the brain.34Data of this kind may throw light on the neurotoxic action of alcohol. An interesting feature of our results is the apparent lack of a uniform pattern in the effects of alcohol: different patients seem to exhibit different sets of pathological ERP parameters, among which there was no correlation. Though further work using a more appropriate experimental design is needed to confirm this finding, it is in keeping with the results of other studies carried out using other methodologies. The clinical effects of chronic alcohol consumption vary greatly from one individual to another: many abusive drinkers do not become alcoholic, and in those who do, alcoholism can take various forms. Even among alcoholics with clear alterations of the nervous system, the alterations vary widely; the clinical patterns presented by the patients can be different and include a variable number of neurological complication^.^^ Patients can have different neuropsychological d e f i ~ i t s , ~ - ~ and structural alterations may or may not be observed’; even the only detectable alteration may be dependence on alcohol. As suggested by on the basis of neuropsychological studies, the organic alterations caused by alcohol seem to be a “continuum” rather than a clearly differentiated set of pathological features.

pattern has always been observed to be altered in some alcoholics, but not all studies have found a statistically significant delay in PlOO latency.’6,17The significance of the results seems to depend on the severity of the patients’ neurological alterations. l8 The lengthening of the N2 and P3 latencies that we observed in alcoholics agrees with what has been reported in previous ~ t u d i e s , ’ but ~ - ~we ~ did not find the reduction in the N2-P3 amplitude reported by Begleiter et al.25A possible explanation for this discrepancy could lie in differences in the characteristics of the patients or in the paradigms used. The finding of an increased Nl-P2 amplitude in our work was unexpected and further complicates interpretation of the data available for early LAEP components. Buchsbaum and Ludwig26and Von K n ~ r r i n gfound ~ ~ that alcoholics presented with repeated visual stimuli had increased PI and N1 or P1-N1 amplitudes. Others found increased amplitudes for the early VEP components (N60P80 and P80-N 1 10) and decreased amplitudes for the late components (N1 10-PI90) when flashesz8or geometrical were used as stimuli. Pfefferbaum and coworkers reported finding equal amplitudes in alcoholics and their controls for N1 and a nonsignificantly greater P2 amplitude in the alcoholics,22and equal peak-to-peak Nl;P2 amplitudes in both groups.z3Although they found a decrease in the Nl-P2 amplitude in patients after 1 week‘s abstinence in the records obtained from F3, F4, P3, and P4, Salamy et noticed that the amplitudes had nor- Conclusion malized in parietal electrodes 3 weeks later. In short, the In this work we have confirmed the alteration of ERPs type of stimulus, the placement of the electrodes, and the in alcoholic patients. The ability of the multimodal ERP period of abstinence all seem to affect N 1-P2 variations in approach to quantify the relative sensitivity of different

MULTIMODALITY EXPLORATION OF ERPs IN ALCOHOLICS

ERP modes to alcohol effects, and the observation of great interpatient heterogeneity regarding the parameters affected suggests that this approach may be capable of providing valuable information on the degeneration of neural systems in alcoholics. REFERENCES 1. Bergman H: Brain dysfunction related to alcoholism: Some results from the KARTAD Project, in Parsons OA, Butters N, Nathan PE (eds): Neuropsychology of Alcoholism. New York, Guilford Press, 1987, pp 21-44 2. Wilkinson DA: Neuroradiologicalinvestigationsof alcoholism, in Tarter RE, Van Thiel D (eds): Alcohol and the Brain: Chronic Effects. New York, Plenum Press, 1985, pp 183-2 15 3. Miller WR, Saucedo C F Assessment of neuropsychologkal impairment and brain damage in problem drinkers, in Golden CJ, Moses JA, Coffman JA, Miller WR, Strider FD (eds): Clinical Neuropsychology: Interface with Neurologic and Psychiatric Disorders. New York, Grune and Stratton, 1983, pp 141-271 4. Parsons OA: Neuropsychological consequences of alcohol abuse: Many questions-some answers, in Parsons OA, Butters N, Nathan PE (eds):Neuropsychology of Alcoholism. New York, Guilford Press, 1987, p~ 153-175 5. Pojesz B, Begleiter H: Evoked brain potential deficits in alcoholism and aging. Alcohol Clin Exp Res 653-63, 1982 6. Porjesz B, Begleiter H: Evoked brain potentials and alcoholism, in Parsons OA, Butters N, Nathan PE (eds): Neuropsychology of Alcoholism. New York, Guilford Press, 1987, pp 45-63 7. Williams HL: Evoked brain potentials and alcoholism:Questions, hypotheses, new approaches, in Parsons OA, Butters N, Nathan PE (eds): Neuropsychology of Alcoholism. New York, Guilford Press, 1987, pp 103- 128 8. Begleiter H, Pojesz B, Chou C L Auditory brainstem potentials in chronic alcoholics. Science (Wash DC) 21 1:1064-1066, 1981 9. Chan YW, McLeod JG, Tuck RR, Feary PA: Brainstem auditory evoked responses in chronic alcoholics. J Neurol Neurosurg Psychiatry 48:1107-1I12, 1985 10. Chu NS: Computed tomographic correlates of auditory brainstem responses in alcoholics. J Neurol Neurosurg Psychiatry 48:348-353,1985 11. Chu NS, Squires KC, Starr A: Auditory brainstem responses in chronic alcoholic patients. Electroencephalogr Clin Neurophysiol 54418-425, 1982 12. Touchon J, Rondovin G, De Lustrac C , Billiard M, BaldyMoulinier M, Cadilhac J Potentials evoques auditifs du tronc cerebral dans “l’epilepsie ethylique.” Rev ElectroencephalogrNeurophysiol Clin 14~133-137,1984 13. Ikeda A, Tremain K, Sanders M D Neurophysiologkal investigation in optic nerve disease: Combined assessment of the visual evoked response and electroretinogram. Br J Ophthalmol62:227-239, 1978 14. Kriss A, Carrol WM, Blumhardt LD, Halliday AM: Pattern- and flash-evoked potential changes in toxic (nutritional) optic neuropathy, in Coujon J, Mauguitre F, Revol M (eds): Clinical Application of Evoked Potentials in Neurology. New York, Raven Press, 1982, pp 1 1-20 15. Dustman RE, Snyder.WW, Calner DA, Beck EC: The evoked response as a measure of cerebral dysfunction, in Begleiter H (ed): Evoked Brain Potentials and Behavior. New York, Plenum Press, 1979, pp 321364 16. Chan YW, Mcleod JG, Tuck RR, Walsh JG, Perry PA: Visuh

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evoked responses in chronic alcoholics. J Neurol Neurosurg Psychiatry 49:945-950, 1986 17. Janaky N, Benedek G, Drovanovics I: Visual evoked potentials in chronic alcoholics. Electroencephalogr Clin Neurophysiol 50:124P, 1980 18. Posthuma J, Visser SL: Visual evoked potentials and alcoholinduced brain damage, in Courjon J, Mauguiere F, Revol M (eds): Clinical Applications of Evoked Potentials in Neurology. New York, Raven Press, 1982, pp 149-155 19. Johnson R, Pfefferbaum A, Hart T, Kopell BS Cognitive changes in long term alcoholics. Paper presented at the 2 1th Annual Meeting of the Society for Psychophysiological Research, Minneapolis, Minnesota, 1982 20. Johnson R, Pfefferbaum A, Hart T, Kopell BS: P300 latency in chronic alcoholics and depressed patients: A preliminary report. Ann NY Acad Sci 425585-591, 1984 2 1. Kostandov EA, Arsumanov YL, Genkina OA, Restchikova TN, Shostakovich GS: The effects of alcohol on hemispheric functional asymmetry. J Stud Alcohol 43:411-426, 1982 22. Pfefferbaum A, Horvath TB, Roth WT, Kopell BS: Event-related potential changes in chronic alcoholics. Electroencephalogr Clin Neurophysiol47:637-647, 1979 23. Pfefferbaum A, Horvath TB, Roth WT, Clifford ST, Kopell BS: Acute and chronic effects of ethanol on event-related potentials. Adv Exp Med Biol 126:625-639, 1980 24. Porjesz B, Begleiter H, Bihari B, Kissin B: The N2 component of the event-related potentials in abstinent alcoholics. Electroencephalogr Clin Neurophysiol66:121-131, 1987 25. Begleiter H, Porjesz B, Tenner M: Event-related brain potentials and computerized tomography in chronic alcoholics. Wien Z Suchtforschung 2:3-6, 1981 26. Buchsbaum MS, Ludwig AM: Effects of sensory input and alcohol administration on visual evoked potentials in normal subjects and alcoholics, in Begleiter H (ed): Biological Effects of Alcohol. New York, Plenum Press, 1980, pp 561-572 27. Von Knorring L Visual averaged evoked responses in patients suffering from alcoholism. Neuropsychobiology 2:233-238, 1976 28. Porjesz B, Begleiter H: Visual evoked potentials and brain dysfunction in chronic alcoholics, in Begleiter H (ed): Evoked Brain Potentials and Behavior. New York, Plenum Press, 1979, pp 277-301 29. Porjesz B, Begleiter H, Samuelly I: Cognitive deficits in chronic alcoholics and elderly subjects assessed by evoked brain potentials. Acta Psychiatr Scand 62 (Suppl286):15-29, 1980 30. Salamy JG, Wright JR, Faillace LA: Changes in averaged evoked responses during abstention in chronic alcoholics. J Nerv Ment Dis 168:19-25, 1980 3 I . Diaz F, Cadaveira F, Grau C Short- and middle-latency auditory evoked potentials in abstinent chronic alcoholics: Preliminary findings. Electroencephalogr Clin Neurophysiol77: 145- 150, 1990 32. Skerchock JA, Cohen J: Alcoholism, organicity and event-related potentials. Ann NY Acad Sci 425:623-628, 1984 33. Van den Bosch RJ: Contingent negative variation and psychopathology: Frontal-central distribution, an association with performance measures. Biol Psychiatry 18:615-634, 1984 34. Freund G: Neuropathology of alcohol abuse, in Tarter RE, Van Thiel DH (eds): Alcohol and the Brain. New York, Plenum Press, 1985, pp 3-17 35. Ron MA: The brain of alcoholics: an overview, in Parsons OA, Butters N, Nathan PE (eds): Neuropsychology of Alcoholism. New York, Guilford Press, 1987, pp 11-20