Evoked potentials: modifications by classical conditioning.

Visual evoked potentials to a positive discriminative stimulus change systematically during sensory conditioning and extinction. Changes due to conditioning are manifested in the increased amplitude of the late component of the evoked response. This effect is attenuated during extinction and reappears after reconditioning.

Evoked brain potentials as indicators of decision-making.

The effects of decision-making processes on evoked brain potentials recorded at the vertex were studied in human subjects. Significantly different visual evoked potentials to the same physical stimulus were obtained in trails that resulted in different behavioral decisions. The results suggest that certain characteristics of evoked potentials may perhaps be used as indicators of specific behavioral outcomes.

Event-related brain potentials in boys at risk for alcoholism.

Recent neurophysiological findings have demonstrated that abstinent chronic alcoholics manifest deficits in event-related brain potentials. To explore possible biological antecedents of alcoholism the present study examined boys at high risk for alcoholism. Event-related brain potentials were recorded from biological sons of alcoholic fathers and matched control boys. Differences in the P3 component of the potentials were obtained between the high-risk and control subjects.

Auditory brainstem potentials in chronic alcoholics.

Auditory brainstem potentials were recorded from abstinent chronic alcoholics and control subjects. The latencies of peaks II, III, IV, and V were significantly delayed in the alcoholic patients compared to control subjects. Brainstem transmission time was longer in alcoholics than in controls. This study provides systematic evidence that chronic alcohol abuse results in brainstem deficits suggesting possible demyelination of auditory tracts.

Evoked potential correlates of expected stimulus intensity.

The electrophysiological responses to a flash of medium intensity have different wave shapes in trials in which the occurrence of bright stimuli or dim stimuli is expected. When a bright or dim stimulus is signaled, the potentials evoked by the medium stimulus resemble the responses evoked by a real bright or dim flash.

A sex-adjusted and age-adjusted genome screen for nested alcohol dependence diagnoses.

Alcohol dependence is a complex disorder with a substantial genetic contribution to susceptibility. The Collaborative Study on the Genetics of Alcoholism is a multi-site study whose purpose is to detect, localize, and characterize genes contributing to this susceptibility. Previous linkage analyses of the trait of alcohol dependence in Collaborative Study on the Genetics of Alcoholism have used affected sib-pair methods with a dichotomous phenotype definition. In contrast, the analysis in this paper uses a sex-adjusted and age-adjusted multiple threshold liability model. The use of such a model, in that it includes unaffected as well as as affected subjects and in that it utilizes the differential severity of a diagnosis scale, should heuristically be more powerful than a straight affected sib-pair analysis. Three regions of interest are found on chromosome 1 (lod 5.17), chromosome 4 (lod 3.46), and chromosome 8 (lod 4.31). The region on chromosome 1 near the marker D1S532 is in the region previously reported as linked to alcohol dependence and correlated phenotypes in this dataset. The region on chromosome 4 near the alcohol dehydrogenase gene cluster has been reported to be linked to alcohol dependence in other studies, as well as to the alcohol consumption phenotype 'Maximum Number of Drinks in a 24-Hour Period' in this dataset. The region on chromosome 8 near the marker D8S1988 is homologous to a section of rat chromosome 5 to which an alcohol consumption phenotype has been linked.

Familial transmission of substance dependence: alcohol, marijuana, cocaine, and habitual smoking: a report from the Collaborative Study on the Genetics of Alcoholism.

BACKGROUND: Alcoholism and substance dependence frequently co-occur. Accordingly, we evaluated the familial transmission of alcohol, marijuana, and cocaine dependence and habitual smoking in the Collaborative Study on the Genetics of Alcoholism. METHODS: Subjects (n=1212) who met criteria for both DSM-III-R alcohol dependence and Feighner definite alcoholism and their siblings (n=2755) were recruited for study. A comparison sample was also recruited (probands, n=217; siblings, n=254). Subjects were interviewed with the Semi-Structured Assessment for the Genetics of Alcoholism. The familial aggregation of drug dependence and habitual smoking in siblings of alcohol-dependent and non-alcohol-dependent probands was measured by means of the Cox proportional hazards model. RESULTS: Rates of alcohol, marijuana, and cocaine dependence and habitual smoking were increased in siblings of alcohol-dependent probands compared with siblings of controls. For siblings of alcohol-dependent probands, 49.3% to 50.1% of brothers and 22.4% to 25.0% of sisters were alcohol dependent (lifetime diagnosis), but this elevated risk was not further increased by comorbid substance dependence in probands. Siblings of marijuana-dependent probands had an elevated risk of developing marijuana dependence (relative risk [RR], 1.78) and siblings of cocaine-dependent probands had an elevated risk of developing cocaine dependence (RR, 1.71). There was a similar finding for habitual smoking (RR, 1.77 in siblings of habitual-smoking probands). CONCLUSIONS: Alcohol, marijuana, and cocaine dependence and habitual smoking are all familial, and there is evidence of both common and specific addictive factors transmitted in families. This specificity suggests independent causative factors in the development of each type of substance dependence.

Event-related brain potentials to high-incentive stimuli in unmedicated schizophrenic patients.

Schizophrenic patients have been observed to have a significantly diminished P300 component of the event-related potential (ERP). We investigated whether this result would be obtained with high-incentive stimuli. We presented 14 unmedicated patients and 14 controls with two easily identified visual stimuli under three conditions: (i) a nonincentive condition, (ii) under the condition of $1 payment for each correct identification, and (iii) under the condition of $1 payment for each correct identification within a criterion time. The patients responded accurately but showed a significantly reduced P300 in the incentive conditions. We interpret our results as neurophysiological evidence for possible limbic system dysfunction in schizophrenia.

Late positive component amplitude in schizophrenics and alcoholics in two different paradigms.

Abstinent alcoholics, unmedicated schizophrenics, and controls were tested in two paradigms designed to elicit the late positive component. Experiment A used frequent stimuli of differing incentive value and Experiment B used infrequent stimuli of differing perceptual discriminability. Alcoholics and schizophrenics showed late positive components that were significantly reduced in amplitude compared to controls. The patient groups were similar in their late component amplitudes. Control subjects showed a substantially wider response range than the patient groups. The narrow response range in both patient groups was manifested in diminished late component amplitudes to both stimuli in both experiments. The intraclass correlation coefficient of late component amplitudes for both patient groups was significantly greater than that of the controls.

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

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 temporooccipital 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.

Auditory P3a assessment of male alcoholics.

BACKGROUND: P3a amplitude differences between alcoholic and control groups have not been well defined. Because event-related potential (ERP) differences between these groups appear to be influenced by task difficulty, the present study employed a new auditory ERP paradigm, in which target/standard tone discriminability was difficult, with infrequent nontarget stimuli used to elicit the P3a. METHODS: A total of n = 27 male alcoholics and n = 25 male controls were assessed using a three-tone discrimination paradigm, in which the discriminability between the target and standard was difficult, with easily discriminable infrequent nontarget tones also presented. A P3a component with a centro-frontal maximum to the rare nontargets and a P3b with a parietal maximum amplitude to the target stimulus were obtained. Current Source Density (CSD) maps were derived from the potential data and employed to assay topographical differences between subject groups. RESULTS: Alcoholics produced smaller P3a amplitudes than control subjects to the rare nontargets with no peak latency differences observed. The most prominent current sources are apparent more anteriorly for the nontarget compared to the target stimulus in both groups. There were more sources and sinks in the alcoholics than in the control subjects for P3a. A bootstrap analysis method showed that P3a CSD maps evinced distinct topographic distributions between alcoholics and control subjects in all brain regions. CONCLUSIONS: The lower P3a amplitude and weaker sources in alcoholics coupled with less topographic specificity in their CSD maps, suggests disorganized inefficient brain functioning. This global electrophysiological pattern suggests cortical disinhibition perhaps reflecting underlying CNS hyperexcitability in alcoholics.

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

The preattentive automatic processing of 63 alcoholics and 27 controls was evaluated with an auditory inattentive event-related oddball paradigm. We examined the mismatch negativity and the N2-P3 complex. Results showed significantly greater amplitude for N2, P3 and the N2-P3 complex for controls but no individual lead (Fz, Cz, Pz) differences by group. A group-by-lead interaction was found for N2 and for the N2-P3 complex. There were no significant latency differences between groups; however, a significant age-by-group interaction effect on latency was greatest at the Cz electrode. Results reflect a possible aberration of automatic processing in alcoholics because of a defect in the mnemonic template necessary to match with an infrequent deviant stimuli. We also found suggestive evidence of a relative weakness of frontal cortical organization in alcoholics. Future studies are suggested that would help clarify these differences in alcoholics.

Neuroelectric correlates of response production and inhibition in individuals at risk to develop alcoholism.

P300 recordings were made from males at high risk (HR) for alcoholism and low-risk (LR) controls, participating in a visual go/no go reaction time paradigm. The go (button press) and no go (inhibit response) stimuli were large and small forms of the same letters. The LR group had significantly larger go than no go P300 amplitudes in the central, parietal, and temporal regions; the HR group manifested no response differences in any region. In the LR group compared to the HR group, both go and no go response amplitudes were larger over the entire head; no group differences in latencies were observed in any region. Surface energy magnitudes paralleled P300 amplitudes and were also larger in the LR group during both go and no go trials. Our findings indicate that HR individuals manifest widespread P300 amplitude deficits while performing a simple information-processing paradigm. These deficits, which may reflect genetic influences, preceded the onset of alcoholism and may function as a phenotypic marker for its development.

Auditory P3a deficits in male subjects at high risk for alcoholism.

BACKGROUND: Substantial evidence indicates that alcoholism is biologically mediated by a genetic predisposition. As the decreased P300 (P3b) event-related brain potential component does not recover with prolonged abstinence, it is unlikely to be related to drinking history but is more likely to be genetically influenced. This is supported by findings that P3b amplitudes are reduced in subjects at high-risk compared to low-risk for alcoholism. Although there are few studies of P3a in HR subjects, lower P3a amplitudes have been reported with a novel nontarget stimulus paradigm, as well as with a difficult three-stimulus visual paradigm. Using a similar three-tone auditory paradigm in which the discriminability between the target and standard tone is difficult, the P3a component can also be reliably elicited with a rare nontarget perceptually distinct stimulus. This technique was employed in young adult subjects at low-risk and high-risk for alcoholism. METHODS: A total of 17 low-risk and 24 high-risk male subjects were employed as subjects in an auditory paradigm that yielded a large amplitude P3a with a centro-frontal maximum to the nontarget and a robust low amplitude prolonged P3b with a parietal maximum amplitude to the target stimulus. Current source density maps were derived to assess topographic differences between low-risk and high-risk subjects. RESULTS: The high-risk group manifested significantly lower P3a amplitudes than the low-risk group at the frontal electrodes to rare nontarget stimuli. High-risk subjects also demonstrated a more disorganized current source density map for P3a compared to low-risk subjects. CONCLUSIONS: The reduction of P3a in the high-risk group may be due to cortical dysfunction including the frontal and prefrontal cortex. The lower P3a amplitude coupled with more disorganized current source density maps suggest inefficient brain functioning in high-risk subjects.

Electrophysiological evidence of memory impairment in alcoholic patients.

In a series of event-related potential (ERP) studies, we have consistently demonstrated an ERP component correlate of visual short-term memory. There have been frequent reports on the deficits of information encoding, retention, and retrieval in chronic alcoholics. In the present study, we investigated that the ERP mnemonic effects could be influenced by long-term alcohol abuse. ERP data were recorded from 48 controls and 77 alcoholics while the subjects performed a modified delayed matching to sample paradigm using a series of object pictures as stimuli. The alcoholics completed the task with more errors and longer response times than the controls. The major differences in the evoked potentials between the two groups are found at the temporo-occipital and frontal regions in the sample and nonmatching trials, and mostly prominent in the right hemisphere. The current study indicates that the ERP technique can be a useful tool to index short-term memory. The ERP mnemonic effect difference between the two groups may be a reflection of a working memory deficit caused by long-term alcohol abuse. Our data also suggest right hemisphere dysfunction in alcoholics, with deficits in information encoding.

Visual P3a in male subjects at high risk for alcoholism.

BACKGROUND: Voltage of the P300 component of event-related potentials (ERPs) has been proposed as a phenotypic marker of risk for alcoholism. P3a elicited by intrusive events is important in the context of deficits in inhibition found during psychophysiological and behavioral evaluations in children of alcoholics. METHODS: ERPs were recorded from a group of adult children of alcoholics (n = 26) and controls (n = 23) with a three-stimulus visual oddball paradigm. The task required a difficult perceptual discrimination between a frequent (.80) vertical line and an infrequent (.10) 2 degrees tilted line (target). An easily discriminable nontarget infrequent horizontal line also occurred (.10). Subjects were required to press a button to the target. P3a was compared using mixed-model ANCOVAs at 31 sites organized in 5 scalp regions. Current source density (CSD) maps were also analyzed. RESULTS: High-risk (HR) subjects manifested reduced P3a amplitudes compared to controls at frontal, central, parietal, and temporal electrodes. CSD analyses supported these findings with group differences found for all the scalp regions. CONCLUSIONS: The results are discussed in relation to previous HR studies. P3a reductions may be related to deficits in neuronal inhibition during stimulus processing. These results suggest that P3a amplitude may be important as a marker for vulnerability to alcoholism.

Frontal P300 decrements, alcohol dependence, and antisocial personality disorder.

BACKGROUND: The purpose of this study was to examine the independent and interactive effects of alcohol dependence, antisocial personality disorder (ASPD), and age on brain function. METHODS: P300 event-related potentials (ERPs) were recorded from 393 alcohol-dependent and 170 non-alcohol-dependent adults while they performed a visual oddball task. The two subject groups were further subdivided based upon age and the presence/absence of ASPD. RESULTS: Alcohol dependence was associated with a significant P300 amplitude decrement at anterior electrode sites only. Antisocial personality disorder was also associated with reduced P300 amplitudes at anterior electrode sites; however, the effects were only significant among subjects 30 years of age or younger. To validate this association between ASPD and P300 amplitude a correlational analysis was performed; the correlation between anterior P300 amplitude and the total number of childhood conduct disorder and adult ASPD symptoms was significant. CONCLUSIONS: The P300 amplitude decrement found at anterior electrode sites among subjects with ASPD is consistent with the results of numerous ERP, neuroimaging, or neuropsychologic studies of anterior brain function. Our study is unique in suggesting that the effects of ASPD on anterior brain function are best detected during early adulthood. The study also suggests that the detrimental neurophysiologic effects of alcohol dependence predominantly involve the anterior brain.

Ethanol-induced alterations in electroencephalographic activity in adult males.

The present investigation examined the effects of placebo (P), low-dose (LD), and high-dose (HD) ethanol on electroencephalographic (EEG) activity in 21 healthy, adult males (X = 22.7 years). Only one condition (P, LD, or HD) was presented per day and the condition order was randomized. For each subject, blood-alcohol levels measured via breathalyzer and EEG activity, using the entire 10/20 International System, were recorded both prior to and at intervals of 35, 70, 105, and 140 minutes after P, LD, or HD administration. The Fast Fourier Transform was used to calculate power spectral densities for each EEG recording. Measures of the relative areas under the power spectral curve were made for each of the following frequency bands: slow alpha (7.5 to 10 Hz); fast alpha (10.5 to 13.0 Hz); slow beta (13.5 to 19.5 Hz); and fast beta (20 to 26 Hz) at electrodes F3, F4, C3, C4, P3, P4, O1, and O2. Repeated-measures multivariate analysis of variance performed on normalized relative area values revealed that ethanol had significant effects on EEG activity at anterior sites: frontal (F3, F4) and central (C3, C4) that presented as increased activity in the slow alpha frequency band. These results suggest a differential responsivity of both cortical region and EEG frequency band to the effects of ethanol ingestion.

A genome screen of maximum number of drinks as an alcoholism phenotype.

The Collaborative Study on the Genetics of Alcoholism (COGA) is a multicenter research program to detect and map susceptibility genes for alcohol dependence and related phenotypes. The measure M of "maximum number of drinks consumed in a 24-hour period" is closely related to alcoholism diagnosis in this dataset and provides a quantitative measure to grade nonalcoholic individuals. Twin studies have shown log(M) to have a heritability of approximately 50%. Genome screens for this trait were performed in two distinct genotyped samples (wave 1 and wave 2), and in the combined sample. MAPMAKER/SIBS was used to carry out Haseman-Elston based regression analyses. On chromosome 4, an unweighted all-pairs multipoint LOD of 2.2 was obtained between D4S2407 and D4S1628 in wave 1; in wave 2, the region flanked by D4S2404 and D4S2407 gave a LOD of 1.5. In the combined sample, the maximal LOD was 3.5 very close to D4S2407. This evidence for linkage is in the region of the alcohol dehydrogenase gene cluster on chromosome 4. These findings on chromosome 4 are consistent with a prior report from COGA in which strictly defined nonalcoholic subjects in wave 1 were analyzed. The present analysis on log(M) allows more individuals to be included and thus is potentially more powerful.

Heritability of event-related brain potentials in families with a history of alcoholism.

Event-related brain potentials (ERPs) are altered in patients with a variety of psychiatric disorders and may represent quantitative correlates of disease liability that are more amenable to genetic analysis than disease status itself. Estimates of heritability are presented for amplitude and latency of the N1 and P3 components of the ERP measured at 19 scalp locations in response to visual and auditory stimuli for 604 individuals in 100 pedigrees ascertained as part of the Collaborative Study on the Genetics of Alcoholism. Significant heritabilities were found for visual P3 amplitude in response to all stimuli and for visual P3 latency in response to target and novel, but not non-target, stimuli. Heritability of visual N1 latencies was uniformly low, whereas heritability of visual N1 amplitude was significant for all electrodes in response to the non-target stimuli but only for posterior electrodes in the other two stimulus conditions. Heritabilities for auditory target P3 were similar to those of the visual stimuli, with auditory target P3 amplitudes and latencies both demonstrating significant heritability. For auditory P2 in response to non-target stimuli, peak amplitude was heritable, but latency was not. Auditory N1 amplitude and latency were significantly heritable for both target and non-target conditions and did not demonstrate the anterior/posterior patterning obtained for visual N1 amplitude. This study represents the first systematic assessment of heritability of these potential neurophysiological markers in families with a history of alcoholism and suggests that many of these ERP phenotypes have heritabilities strong enough to justify genomic screening for loci jointly influencing ERP abnormalities and liability to alcoholism.