Electroencephalography and Clinical Neurophysiology, 1979, 47:637--647
637
© Elsevier/North-Holland Scientific Publishers, Ltd.
EVENT-RELATED POTENTIAL CHANGES IN CHRONIC ALCOHOLICS 1 ADOLF PFEFFERBAUM, THOMAS B. HORVATH, WALTON T. ROTH and BERT S. KOPELL Laboratory of Clinical Psychopharmacology and Psychophysiology, Veterans Administration Medical Center, Palo Alto and Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif. 94305 (U.S.A.)
(Accepted for publication: April 10, 1979)
The long term excessive use of alcohol is injurious to physical and mental health. While peripheral somatic sequelae are often the most visible changes, central nervous system disease is also prominent. Alcohol-related dementia was seen in 9% of a series of consecutive patients screened for treatment in an outpatient program for alcoholics (Horvath 1975} and subtle forms of cognitive malfunction are even more c o m m o n (Cutting 1978). Alcohol-associated CNS disease can involve sub-cortical structures as seen in the Wernicke-Korsakoff Syndrome (Victor et al. 1971) and cortical structures in the form of atrophy, as demonstrated by pneumoencephalography (Haug 1968; Brewer and Perrett 1971), computerized axial tomography (Carlen et al. 1977), and examination at postmortem (Courville 1966; Neuberger 1957). It might be expected that the structural alterations induced by chronic alcoholism are accompanied by functional alterations observable in the EEG and behavioral performance. There are, indeed, behavioral changes reflective of long term alcoholism. The clinical EEG, however, can be 'normal' despite structural changes (i.e., cerebral atrophy as demon-
1 This work was supported by the Medical Research Service of the Veterans Administration and NIMH Specialized Research Center Grant MH 30854. Reprint requests should be addressed to: Adolf Pfefferbaum, M.D., Psychiatry Service, 116A3, VA Medical Center, Palo Alto, Calif. 94304.
strated by CT scan), especially in alcoholics under 60 years of age (Newman 1978). Similarly, the efforts to demonstrate significant increase in EEG abnormalities in patients with uncomplicated alcoholism as compared to normals have been relatively unsuccessful (Begleiter and Platz 1972). Sensory evoked potentials have been used extensively to demonstrate the acute effects of ethanol on the CNS (Salamy 1973; Porjesz and Begleiter 1975; Roth et al. 1977; Pfefferbaum et al. 1979). This approach has been less widely used to investigate the chronic effects of ethanol, and the results are less conclusive (Malerstein and Callaway 1969; von Knorring 1976; Coger et al. 1976). Eventrelated potentials (ERPs), especially the P3 component which has been linked in m a n y studies with cognitive and perceptual functioning (Roth et al. 1976, 1978; Kutas etal. 1977), may provide the functional evidence for structural deficits which have not been demonstrated with sensory evoked potentials. Goodin et al. (1978a) found a high correlation between impaired cognitive functioning as seen in dementia, and P3 latency and amplitude characteristics. Cognitive impairm e n t is also a characteristic of some phases of chronic alcoholism (Goodwin and Hill 1975). It is especially prominent in those persons with a greater than ten year history of alcoholic drinking, and with large life-time volumes of alcohol consumption (Eckardt et al. 1978). Therefore, it is proposed that the latency and amplitude of the P3 c o m p o n e n t
638 may serve as clinical indicators in assessing CNS deterioration in an alcoholic population. The current study was designed to test the hypothesis th at there are CNS functional impairments associated with chronic alcoholism which can be d e m o n s t r a t e d with eventrelated potentials.
Methods Ten chronic alcoholics and ten age and sex matched controls participated in this experiment. The alcoholics were all inpatients in an alcohol t r e a t m e n t program at the Palo Alto Veterans Administration Medical Center. The alcoholics had been abstinent from alcohol for at least two weeks {mean = 21 days) and o ff all psychotropic medications for at least ten days (mean = 15 days). The controls had no alcohol in the 24 h prior to testing. The alcoholics had a ten year or greater history of alcoholic drinking and m e t the Research Diagnostic Criteria (RDC) for alcoholism (Spitzer et al. 1977). Subjects with manifest CNS pathology on neurological examination were excluded b u t several patients with mild peripheral n e u r o p a t h y were included. Neuropsychologic functioning was assessed with the Halstead--Reitan screening bat t er y (Golden 1978). The ALCADD test (Manson 1949) was used to quantify drinking behavior. The alcoholics had a mean ALCADD score of 52 (range o f 41--61); the controls were social drinkers with ALCADD scores less than 10. The alcoholics were aged 42--55 years (mean = 50.1); the controls were aged 42--58 years (mean = 4 8 . 2 ) . Patients and controls were excluded if th ey had significant renal, pulm o n a r y , or cardiovascular disease. All subjects had auditory thresholds less than 20 dB at 1000 Hz bilaterally. For the EEG testing the subjects were seated in a dimly lit acoustical chamber and auditory stimuli were delivered t h r o u g h s t e r e o headphones. EEG was recorded f r om Fz, Cz, and Pz electrode placements, referenced to
A. PFEFFERBAUM ET AL. linked ears, and amplified with a nominal bandpass of 0.03--100 Hz (3 dB points of 6 dB per octave roll-off rate). EOG was recorded from above and below the right eye with the same bandpass. A PDP-12 minic o m p u t e r was used to generate the stimuli and to collect the reaction time, EEG, and EOG. The data were collected at 4 msec sampling intervals. The P3 paradigm was a version of the paradigm of Rot h et al. (1978). It consisted of a series of computer-generated tone bursts 40 msec in duration with 8 msec onset and offset envelopes which prevented high frequency speaker transients. The stimuli were delivered at 70 dB above sensation threshold with an interstimulus interval (ISI) of one second. Tones o f 1000 Hz, 500 Hz, and 2000 Hz were presented random l y with the 1000 Hz tone occurring 72% of the time, and the 500 Hz and 2000 Hz tones each occurring 14% of the time. The 1000 Hz tone, referred to as the F r e q u e n t Stimulus, was presented 320 times. The 500 Hz and 2000 Hz tones, referred to as Infrequent Stimuli, were each presented 60 times in the series. The subject was instructed to press a reaction-time key when one of the t w o types of infrequent tones occurred, i.e., the subject was told, 'press when y o u hear the high-pitched tone'. In this case, the 2000 Hz t o n e would be the 'target' and the 500 Hz t one would be the 'non-target' I n f r e q u e n t Stimulus. Thus, there were three classes of stimuli: Frequent , I n f r e q u e n t target and I n f r e q u e n t non-target. Half the subjects had the 500 Hz tone as target and half had 2000 Hz targets. Speed and accuracy were emphasized equally in the task instructions. ERPs to the F r e q u e n t Stimuli were averaged on-line across all four leads. Trials t hat saturated the analog to digital (A--D) converter for any lead were rejected. The Frequent Stimuli produced an evoked potential which had a p r o m i n e n t N1 and P2 but no P3. The N1 was defined as the largest negative peak from 75 to 150 msec; P2 was the largest positive peak from N1 to 275 msec. The N1 and P2 c o m p o n e n t s of the ERPs to the Fre-
ERP CHANGES IN CHRONIC ALCOHOLICS quent Stimuli were determined on unfiltered data (0.03--100 Hz bandpass). The single trial EEG responses to the two classes of Infrequent Stimuli (target and non-target) were recorded on-line and ERP averages and single trial analyses were subsequently performed off-line. ERPs to the Infrequent Stimuli were constructed as follows. Trials were rejected if the A-D converter was saturated for any lead. Target trials in which the reaction time was less than 100 or greater than 1000 msec were rejected. Non-target trials with reaction time responses were also rejected. The stored EEG and EOG data were reduced to 8 msec intervals by omitting every other point. The data were subjected to a digital filter which approximated an ideal zero phase-shift filter when applied to stored data (Wilcock and Kirsner 1969). The digital filtering produced a high frequency c u t o f f at 6.8 Hz (down 3 dB). EOG artifact was dealt with by calculating a fractional representation of EOG activity at each EEG electrode site from a calibration run of eye blinking for each subject separately (Corby and Kopell 1972). The EOG was multiplied by the factor for each lead (Fz, Cz, Pz) and this resultant activity was subtracted from the EEG. The latency and amplitude of the P3 c o m p o n e n t were determined by computer algorithm which identified the largest positive point between 280 and 520 msec. The P3 amplitude was calculated by measuring the voltage difference between the prestimulus baseline and the P3 peak. The single trial adaptive filter analysis (Woody 1967) was performed only on the Pz recorded data. Exclusion and digital filtering were as above. The EOG subtraction factor was determined again for the Pz lead from the data collected during the run and the EOG was subtracted for each single trial. The adaptive filtering proceeded as follows: (1) the peak P3 latency of the averaged ERP was determined by identifying the largest positive point between 280 and 520 msec; (2) a portion of the averaged ERP -- the P3 peak -+ 128 msec -- was defined as a template; (3) the 256
639 msec wide template (P3 peak + 128 msec) was moved at 8 msec increments across each single trial; (4) the 'distance' (time in 8 msec increments) moved by the template in order to produce the highest correlation between the template and the single trial was determined; (5) the single trial P3 latency was calculated by adding this 'distance' to the template P3 latency; (6) a new average was created by aligning the single trials on the points of maxim u m correlation (e.g., aligning each single trial with every other on its P3 latency); (7) the operation then returned to step 1, and determined a new template from this new average; (8) the entire process was repeated for a total of three iterations. The target and non-target responses were analyzed separately. In addition, the correlation between the reaction time (RT) and the latency of the point of m a x i m u m template correlation for each single trial was determined. This produced an estimate of the correlation between the RT and P3 latency for each subject based on his single trial data.
Results
The alcoholics and controls did not differ significantly in the number of correct target responses, false alarms (button presses to nontarget stimuli), or reaction time (see Table I). The controls had a mean reaction time of 345 msec, and the alcoholics had a mean reaction time of 328 msec (t = 0.70, P = 0.50). Six of the alcoholics had normal scores (less than 120) on the Halstead-Reitan screening battery, one was 'borderline' (180) and three had TABLE I Behavioral data.
Alcoholics Controls
% Non-target
% Target
Mean
false alarms
hits
reaction time (msec)
0.67%
93.8%
0.16%
96.8%
328 345
640
A. PFEFFERBAUM ET AL.
AMPLITUDE N 1 and P2
d e f i n i t e p a t h o l o g y (greater t h a n 2 2 0 ) . O n l y five c o n t r o l s w e r e t e s t e d a n d all h a d n o r m a l scores o n this b a t t e r y .
8-
F values from analyses of variance: frequent stimuli.
*** P < 0.001.
P2
4-
>
2-
"O
0
-.,= Q.
, O
150-
C (D J
TABLE II
N1 amplitude N1 latency P2 amplitude P2 latency
Alcoholics o- - --o Controls
•
6-
Averaged ERPs Frequent stimuli. T a b l e I I p r e s e n t s t h e results o f t w o - w a y analyses o f variance ( g r o u p = alcoholic vs. c o n t r o l , lead = Fz, Cz, Pz) perf o r m e d o n t h e N1 a n d P2 a m p l i t u d e a n d l a t e n c y . T h e r e was a significant lead e f f e c t f o r N1 a n d P2 a m p l i t u d e ( P < 0 . 0 0 1 ) , r e f l e c t i n g t h e larger a m p l i t u d e f o r b o t h c o m p o n e n t s at Cz. T h e r e w e r e n o statistically significant g r o u p d i f f e r e n c e s (alcoholics did n o t d i f f e r f r o m n o r m a l s ) n o r g r o u p × lead i n t e r a c t i o n s f o r t h e a m p l i t u d e or l a t e n c y o f N1 or P2. T h e s e d a t a are graphically p r e s e n t e d in Figs. 1 and 2. Infrequent stimuli. B o t h t h e t a r g e t a n d n o n t a r g e t I n f r e q u e n t Stimuli p r o d u c e d large, easily i d e n t i f i a b l e P3 c o m p o n e n t s in t h e ERPs. T h e o n l y e x c e p t i o n was t h e t a r g e t cond i t i o n f o r o n e o f t h e c o n t r o l s w h i c h was n o t i n c l u d e d in t h e analyses. T h e a m p l i t u d e and l a t e n c y o f t h e P3 to t h e t a r g e t a n d n o n - t a r g e t stimuli w e r e a n a l y z e d b y s e p a r a t e analyses o f variance p r e s e n t e d in T a b l e III. T h e t a r g e t stimuli p r o d u c e d a P3 in t h e alcoholics w h i c h was significantly p r o l o n g e d in l a t e n c y ( P < 0 . 0 2 ) b u t did n o t d i f f e r in a m p l i t u d e as c o m p a r e d t o t h e c o n t r o l s . T h e r e w e r e significant lead e f f e c t s f o r b o t h amplit u d e a n d l a t e n c y o f t h e P3 t o t h e t a r g e t stimuli across t h e t w o g r o u p s o f s u b j e c t s (alcoholics a n d c o n t r o l s ) . I t can be seen in Figs. 3 a n d 4 t h a t t h e P3 t o t h e t a r g e t s t i m u l u s was
T .~-~.
Group
Lead
Group X lead
0.03 3.75 1.39 0.24
8.61 *** 0.01 13.23 *** 1.86
1.22 0.01 0.56 0.49
100-
50
,
,
I
Fz
Cz
Pz
Fig. 2. Group mean (alcoholics and controls) N1 and P2 latencies for Fz, Cz, and Pz recorded ERPs to the Frequent Stimuli.
E R P C H A N G E S IN C H R O N I C A L C O H O L I C S
641
P3 LATENCY
TABLE III F values from analyses of variance: infrequent stimuli. Group
Lead
Group × lead
6.44 ** 20.8 ***
0.19 0.38
•
~ Alcoholics
c---o Controls
450425-
Target P3 a m p l i t u d e P3 l a t e n c y
0.36 6.72 *
O (D
400-
E
Non-target P3 a m p l i t u d e P3 l a t e n c y
1.07 1 6 . 1 1 ***
8.65 *** 0.03
1.90 0.86
O c(D ._1
* P < 0.02. ** P < 0.01. * * * P < 0.001.
375350325300
larger and later at Pz, smaller at Cz and smallest at Fz. The P3 to the non-target stimuli was markedly prolonged in latency for the alcoholics as compared to the controls ( P < 0.001). Like the target stimuli, the non-target stimuli produced no significant P3 amplitude
P3 AMPLITUDE 20-- Alcoholics o--.o Controls
•
I
I'
I
Fz Cz Pz Target
I
Fz
I
I
Cz Pz
Non-target
Fig. 4. Group mean (alcoholics and controls) I)3 latencies for Fz, Cz, and Pz recorded ERPs to the target and non-target Infrequent Stimuli.
difference between the alcoholics and controis. The non-target stimuli also produced significant lead effects with the P3 amplitude larger over parietal than frontal recording sites. There were no statistically significant group × lead interactions for the target or non-target stimuli.
Single trial analysis >
T
:-q
"10
.__=
637
© Elsevier/North-Holland Scientific Publishers, Ltd.
EVENT-RELATED POTENTIAL CHANGES IN CHRONIC ALCOHOLICS 1 ADOLF PFEFFERBAUM, THOMAS B. HORVATH, WALTON T. ROTH and BERT S. KOPELL Laboratory of Clinical Psychopharmacology and Psychophysiology, Veterans Administration Medical Center, Palo Alto and Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif. 94305 (U.S.A.)
(Accepted for publication: April 10, 1979)
The long term excessive use of alcohol is injurious to physical and mental health. While peripheral somatic sequelae are often the most visible changes, central nervous system disease is also prominent. Alcohol-related dementia was seen in 9% of a series of consecutive patients screened for treatment in an outpatient program for alcoholics (Horvath 1975} and subtle forms of cognitive malfunction are even more c o m m o n (Cutting 1978). Alcohol-associated CNS disease can involve sub-cortical structures as seen in the Wernicke-Korsakoff Syndrome (Victor et al. 1971) and cortical structures in the form of atrophy, as demonstrated by pneumoencephalography (Haug 1968; Brewer and Perrett 1971), computerized axial tomography (Carlen et al. 1977), and examination at postmortem (Courville 1966; Neuberger 1957). It might be expected that the structural alterations induced by chronic alcoholism are accompanied by functional alterations observable in the EEG and behavioral performance. There are, indeed, behavioral changes reflective of long term alcoholism. The clinical EEG, however, can be 'normal' despite structural changes (i.e., cerebral atrophy as demon-
1 This work was supported by the Medical Research Service of the Veterans Administration and NIMH Specialized Research Center Grant MH 30854. Reprint requests should be addressed to: Adolf Pfefferbaum, M.D., Psychiatry Service, 116A3, VA Medical Center, Palo Alto, Calif. 94304.
strated by CT scan), especially in alcoholics under 60 years of age (Newman 1978). Similarly, the efforts to demonstrate significant increase in EEG abnormalities in patients with uncomplicated alcoholism as compared to normals have been relatively unsuccessful (Begleiter and Platz 1972). Sensory evoked potentials have been used extensively to demonstrate the acute effects of ethanol on the CNS (Salamy 1973; Porjesz and Begleiter 1975; Roth et al. 1977; Pfefferbaum et al. 1979). This approach has been less widely used to investigate the chronic effects of ethanol, and the results are less conclusive (Malerstein and Callaway 1969; von Knorring 1976; Coger et al. 1976). Eventrelated potentials (ERPs), especially the P3 component which has been linked in m a n y studies with cognitive and perceptual functioning (Roth et al. 1976, 1978; Kutas etal. 1977), may provide the functional evidence for structural deficits which have not been demonstrated with sensory evoked potentials. Goodin et al. (1978a) found a high correlation between impaired cognitive functioning as seen in dementia, and P3 latency and amplitude characteristics. Cognitive impairm e n t is also a characteristic of some phases of chronic alcoholism (Goodwin and Hill 1975). It is especially prominent in those persons with a greater than ten year history of alcoholic drinking, and with large life-time volumes of alcohol consumption (Eckardt et al. 1978). Therefore, it is proposed that the latency and amplitude of the P3 c o m p o n e n t
638 may serve as clinical indicators in assessing CNS deterioration in an alcoholic population. The current study was designed to test the hypothesis th at there are CNS functional impairments associated with chronic alcoholism which can be d e m o n s t r a t e d with eventrelated potentials.
Methods Ten chronic alcoholics and ten age and sex matched controls participated in this experiment. The alcoholics were all inpatients in an alcohol t r e a t m e n t program at the Palo Alto Veterans Administration Medical Center. The alcoholics had been abstinent from alcohol for at least two weeks {mean = 21 days) and o ff all psychotropic medications for at least ten days (mean = 15 days). The controls had no alcohol in the 24 h prior to testing. The alcoholics had a ten year or greater history of alcoholic drinking and m e t the Research Diagnostic Criteria (RDC) for alcoholism (Spitzer et al. 1977). Subjects with manifest CNS pathology on neurological examination were excluded b u t several patients with mild peripheral n e u r o p a t h y were included. Neuropsychologic functioning was assessed with the Halstead--Reitan screening bat t er y (Golden 1978). The ALCADD test (Manson 1949) was used to quantify drinking behavior. The alcoholics had a mean ALCADD score of 52 (range o f 41--61); the controls were social drinkers with ALCADD scores less than 10. The alcoholics were aged 42--55 years (mean = 50.1); the controls were aged 42--58 years (mean = 4 8 . 2 ) . Patients and controls were excluded if th ey had significant renal, pulm o n a r y , or cardiovascular disease. All subjects had auditory thresholds less than 20 dB at 1000 Hz bilaterally. For the EEG testing the subjects were seated in a dimly lit acoustical chamber and auditory stimuli were delivered t h r o u g h s t e r e o headphones. EEG was recorded f r om Fz, Cz, and Pz electrode placements, referenced to
A. PFEFFERBAUM ET AL. linked ears, and amplified with a nominal bandpass of 0.03--100 Hz (3 dB points of 6 dB per octave roll-off rate). EOG was recorded from above and below the right eye with the same bandpass. A PDP-12 minic o m p u t e r was used to generate the stimuli and to collect the reaction time, EEG, and EOG. The data were collected at 4 msec sampling intervals. The P3 paradigm was a version of the paradigm of Rot h et al. (1978). It consisted of a series of computer-generated tone bursts 40 msec in duration with 8 msec onset and offset envelopes which prevented high frequency speaker transients. The stimuli were delivered at 70 dB above sensation threshold with an interstimulus interval (ISI) of one second. Tones o f 1000 Hz, 500 Hz, and 2000 Hz were presented random l y with the 1000 Hz tone occurring 72% of the time, and the 500 Hz and 2000 Hz tones each occurring 14% of the time. The 1000 Hz tone, referred to as the F r e q u e n t Stimulus, was presented 320 times. The 500 Hz and 2000 Hz tones, referred to as Infrequent Stimuli, were each presented 60 times in the series. The subject was instructed to press a reaction-time key when one of the t w o types of infrequent tones occurred, i.e., the subject was told, 'press when y o u hear the high-pitched tone'. In this case, the 2000 Hz t o n e would be the 'target' and the 500 Hz t one would be the 'non-target' I n f r e q u e n t Stimulus. Thus, there were three classes of stimuli: Frequent , I n f r e q u e n t target and I n f r e q u e n t non-target. Half the subjects had the 500 Hz tone as target and half had 2000 Hz targets. Speed and accuracy were emphasized equally in the task instructions. ERPs to the F r e q u e n t Stimuli were averaged on-line across all four leads. Trials t hat saturated the analog to digital (A--D) converter for any lead were rejected. The Frequent Stimuli produced an evoked potential which had a p r o m i n e n t N1 and P2 but no P3. The N1 was defined as the largest negative peak from 75 to 150 msec; P2 was the largest positive peak from N1 to 275 msec. The N1 and P2 c o m p o n e n t s of the ERPs to the Fre-
ERP CHANGES IN CHRONIC ALCOHOLICS quent Stimuli were determined on unfiltered data (0.03--100 Hz bandpass). The single trial EEG responses to the two classes of Infrequent Stimuli (target and non-target) were recorded on-line and ERP averages and single trial analyses were subsequently performed off-line. ERPs to the Infrequent Stimuli were constructed as follows. Trials were rejected if the A-D converter was saturated for any lead. Target trials in which the reaction time was less than 100 or greater than 1000 msec were rejected. Non-target trials with reaction time responses were also rejected. The stored EEG and EOG data were reduced to 8 msec intervals by omitting every other point. The data were subjected to a digital filter which approximated an ideal zero phase-shift filter when applied to stored data (Wilcock and Kirsner 1969). The digital filtering produced a high frequency c u t o f f at 6.8 Hz (down 3 dB). EOG artifact was dealt with by calculating a fractional representation of EOG activity at each EEG electrode site from a calibration run of eye blinking for each subject separately (Corby and Kopell 1972). The EOG was multiplied by the factor for each lead (Fz, Cz, Pz) and this resultant activity was subtracted from the EEG. The latency and amplitude of the P3 c o m p o n e n t were determined by computer algorithm which identified the largest positive point between 280 and 520 msec. The P3 amplitude was calculated by measuring the voltage difference between the prestimulus baseline and the P3 peak. The single trial adaptive filter analysis (Woody 1967) was performed only on the Pz recorded data. Exclusion and digital filtering were as above. The EOG subtraction factor was determined again for the Pz lead from the data collected during the run and the EOG was subtracted for each single trial. The adaptive filtering proceeded as follows: (1) the peak P3 latency of the averaged ERP was determined by identifying the largest positive point between 280 and 520 msec; (2) a portion of the averaged ERP -- the P3 peak -+ 128 msec -- was defined as a template; (3) the 256
639 msec wide template (P3 peak + 128 msec) was moved at 8 msec increments across each single trial; (4) the 'distance' (time in 8 msec increments) moved by the template in order to produce the highest correlation between the template and the single trial was determined; (5) the single trial P3 latency was calculated by adding this 'distance' to the template P3 latency; (6) a new average was created by aligning the single trials on the points of maxim u m correlation (e.g., aligning each single trial with every other on its P3 latency); (7) the operation then returned to step 1, and determined a new template from this new average; (8) the entire process was repeated for a total of three iterations. The target and non-target responses were analyzed separately. In addition, the correlation between the reaction time (RT) and the latency of the point of m a x i m u m template correlation for each single trial was determined. This produced an estimate of the correlation between the RT and P3 latency for each subject based on his single trial data.
Results
The alcoholics and controls did not differ significantly in the number of correct target responses, false alarms (button presses to nontarget stimuli), or reaction time (see Table I). The controls had a mean reaction time of 345 msec, and the alcoholics had a mean reaction time of 328 msec (t = 0.70, P = 0.50). Six of the alcoholics had normal scores (less than 120) on the Halstead-Reitan screening battery, one was 'borderline' (180) and three had TABLE I Behavioral data.
Alcoholics Controls
% Non-target
% Target
Mean
false alarms
hits
reaction time (msec)
0.67%
93.8%
0.16%
96.8%
328 345
640
A. PFEFFERBAUM ET AL.
AMPLITUDE N 1 and P2
d e f i n i t e p a t h o l o g y (greater t h a n 2 2 0 ) . O n l y five c o n t r o l s w e r e t e s t e d a n d all h a d n o r m a l scores o n this b a t t e r y .
8-
F values from analyses of variance: frequent stimuli.
*** P < 0.001.
P2
4-
>
2-
"O
0
-.,= Q.
, O
150-
C (D J
TABLE II
N1 amplitude N1 latency P2 amplitude P2 latency
Alcoholics o- - --o Controls
•
6-
Averaged ERPs Frequent stimuli. T a b l e I I p r e s e n t s t h e results o f t w o - w a y analyses o f variance ( g r o u p = alcoholic vs. c o n t r o l , lead = Fz, Cz, Pz) perf o r m e d o n t h e N1 a n d P2 a m p l i t u d e a n d l a t e n c y . T h e r e was a significant lead e f f e c t f o r N1 a n d P2 a m p l i t u d e ( P < 0 . 0 0 1 ) , r e f l e c t i n g t h e larger a m p l i t u d e f o r b o t h c o m p o n e n t s at Cz. T h e r e w e r e n o statistically significant g r o u p d i f f e r e n c e s (alcoholics did n o t d i f f e r f r o m n o r m a l s ) n o r g r o u p × lead i n t e r a c t i o n s f o r t h e a m p l i t u d e or l a t e n c y o f N1 or P2. T h e s e d a t a are graphically p r e s e n t e d in Figs. 1 and 2. Infrequent stimuli. B o t h t h e t a r g e t a n d n o n t a r g e t I n f r e q u e n t Stimuli p r o d u c e d large, easily i d e n t i f i a b l e P3 c o m p o n e n t s in t h e ERPs. T h e o n l y e x c e p t i o n was t h e t a r g e t cond i t i o n f o r o n e o f t h e c o n t r o l s w h i c h was n o t i n c l u d e d in t h e analyses. T h e a m p l i t u d e and l a t e n c y o f t h e P3 to t h e t a r g e t a n d n o n - t a r g e t stimuli w e r e a n a l y z e d b y s e p a r a t e analyses o f variance p r e s e n t e d in T a b l e III. T h e t a r g e t stimuli p r o d u c e d a P3 in t h e alcoholics w h i c h was significantly p r o l o n g e d in l a t e n c y ( P < 0 . 0 2 ) b u t did n o t d i f f e r in a m p l i t u d e as c o m p a r e d t o t h e c o n t r o l s . T h e r e w e r e significant lead e f f e c t s f o r b o t h amplit u d e a n d l a t e n c y o f t h e P3 t o t h e t a r g e t stimuli across t h e t w o g r o u p s o f s u b j e c t s (alcoholics a n d c o n t r o l s ) . I t can be seen in Figs. 3 a n d 4 t h a t t h e P3 t o t h e t a r g e t s t i m u l u s was
T .~-~.
Group
Lead
Group X lead
0.03 3.75 1.39 0.24
8.61 *** 0.01 13.23 *** 1.86
1.22 0.01 0.56 0.49
100-
50
,
,
I
Fz
Cz
Pz
Fig. 2. Group mean (alcoholics and controls) N1 and P2 latencies for Fz, Cz, and Pz recorded ERPs to the Frequent Stimuli.
E R P C H A N G E S IN C H R O N I C A L C O H O L I C S
641
P3 LATENCY
TABLE III F values from analyses of variance: infrequent stimuli. Group
Lead
Group × lead
6.44 ** 20.8 ***
0.19 0.38
•
~ Alcoholics
c---o Controls
450425-
Target P3 a m p l i t u d e P3 l a t e n c y
0.36 6.72 *
O (D
400-
E
Non-target P3 a m p l i t u d e P3 l a t e n c y
1.07 1 6 . 1 1 ***
8.65 *** 0.03
1.90 0.86
O c(D ._1
* P < 0.02. ** P < 0.01. * * * P < 0.001.
375350325300
larger and later at Pz, smaller at Cz and smallest at Fz. The P3 to the non-target stimuli was markedly prolonged in latency for the alcoholics as compared to the controls ( P < 0.001). Like the target stimuli, the non-target stimuli produced no significant P3 amplitude
P3 AMPLITUDE 20-- Alcoholics o--.o Controls
•
I
I'
I
Fz Cz Pz Target
I
Fz
I
I
Cz Pz
Non-target
Fig. 4. Group mean (alcoholics and controls) I)3 latencies for Fz, Cz, and Pz recorded ERPs to the target and non-target Infrequent Stimuli.
difference between the alcoholics and controis. The non-target stimuli also produced significant lead effects with the P3 amplitude larger over parietal than frontal recording sites. There were no statistically significant group × lead interactions for the target or non-target stimuli.
Single trial analysis >
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