Arthur T. Stimus

Alcoholism is a disinhibitory disorder : neurophysiological evidence from a Go/No-Go task

Response inhibition is considered a core dimension in alcoholism and its co-existing disorders. The major objective of this study is to compare the magnitude and spatial distribution of ERP components during response activation and inhibition in alcoholics (N = 30) and normal controls (N = 30) using a visual Go/No-Go task. The results indicate that alcoholics manifest a decreased P3(00) amplitude during Go as well as No-Go conditions. The difference between Go and No-Go processing was more evident in controls than in alcoholics. The topography of current source density in alcoholics during the P3 response was found to be very different from that of normals, suggesting that alcoholics perhaps activated inappropriate brain circuitry during cognitive processing. The significantly reduced No-Go P3 along with the relatively less anteriorized CSD topography during No-Go condition suggests poor inhibitory control in alcoholics. It is proposed that the No-Go P3, the electrophysiological signature of response inhibition, can be considered as an endophenotypic marker in alcoholism.

Linkage and linkage disequilibrium mapping of ERP and EEG phenotypes.

Linkage analyses of highly heritable electrophysiological phenotypes (EEG, ERP) that can potentially identify individuals at risk for alcoholism were performed on a large sample of families with a high density of alcohol dependence as part of the Collaborative Study on the Genetics of Alcoholism (COGA); these genetic findings are summarized. Quantitative trait loci (QTLs) were identified for several ERP characteristics (P300, N100, N400) and for the beta frequencies of the EEG where we report linkage and linkage disequilibrium at a GABA(A) receptor gene on chromosome 4. Genetic analyses of ERPs suggest that several regions of the human genome contain genetic loci related to the generation of N100, N400 and P300, which are possible candidate loci underlying the functional organization of human neuroelectric activity. The advent of genomics and proteomics and a fuller understanding of gene regulation, will open new horizons on the critical electrical events so essential for human brain function.

Event-related oscillations in offspring of alcoholics: neurocognitive disinhibition as a risk for alcoholism.

BACKGROUND Event-related oscillations (EROs) are increasingly being used to assess neurocognitive functioning in normal and clinical populations. The current study compares different frequency activities in offspring of alcoholics (OA) and in normal control subjects (NC) to examine whether the OA group exhibits any abnormality in oscillatory activity while performing a Go/NoGo task. METHODS The S-transform algorithm was employed to decompose the electroencephalographic (EEG) signals into different time-frequency bands, and the oscillatory responses in the P300 time window (300-700 milliseconds) were statistically analyzed in both groups. RESULTS The OA group manifested significantly decreased activity in delta (1-3 Hz), theta (4-7 Hz), and alpha1 (8-9 Hz) bands during the NoGo condition, as well as reduced delta and theta activity during the Go condition. This reduction was more prominent in the NoGo than in the Go condition. CONCLUSIONS The decreased response in delta, theta, and alpha1 oscillations, especially during the NoGo condition in high-risk individuals, is perhaps suggestive of cognitive and neural disinhibition and may serve as an endophenotypic marker in the development of alcoholism and/or other disinhibitory disorders.

S-transform time-frequency analysis of P300 reveals deficits in individuals diagnosed with alcoholism

OBJECTIVE Decomposition of event-related potential (ERP) waveforms using time-frequency representations (TFRs) is becoming increasingly common in electrophysiology. The P300 potential is an important component of the ERP waveform and has been used to study cognition as well as psychiatric disorders such as alcoholism. In this work, we aim to further understand the nature of the event-related oscillation (ERO) components which form the P300 wave and how these components may be used to differentiate alcoholic individuals from controls. METHODS The S-transform decomposition method is used to derive TFRs from single trial and trial-averaged ERP data acquired during a visual oddball task. These TFRs are averaged within time and frequency windows to provide ERO measures for further investigation. ERO measures are compared with conventional ERP amplitude measures using correlation analyses. Statistical analyses was performed with MANOVA and stepwise logistic regressions to contrast an age-matched sample of control (N=100) and alcoholic male subjects (N=100). RESULTS The results indicate that the P300 waveform, elicited using infrequent salient stimuli, is composed of frontal theta and posterior delta activations. The frontal theta activation does not closely correspond to any of the conventional ERP components and is therefore best analyzed using spectral methods. Between group comparisons and group predictions indicate that the delta and theta band EROs, which underlie the P300, show deficits in the alcoholic group. Additionally, each band contributes unique information to discriminate between the groups. CONCLUSIONS ERO measures which underlie and compose the P300 wave provide additional information to that offered by conventional ERP amplitude measures, and serve as useful genetic markers in the study of alcoholism. SIGNIFICANCE Studying the ERP waveform using time-frequency analysis methods opens new avenues of research in electrophysiology which may lead to a better understanding of cognitive processes, lead to improved clinical diagnoses, and provide phenotypes/endophenotypes for genetic analyses.

Neurocognitive deficits in male alcoholics: An ERP/sLORETA analysis of the N2 component in an equal probability Go/NoGo task

In alcoholism research, studies concerning time-locked electrophysiological aspects of response inhibition have concentrated mainly on the P3 component of the event-related potential (ERP). The objective of the present study was to investigate the N2 component of the ERP to elucidate possible brain dysfunction related to the motor response and its inhibition using a Go/NoGo task in alcoholics. The sample consisted of 78 abstinent alcoholic males and 58 healthy male controls. The N2 peak was compared across group and task conditions. Alcoholics showed significantly reduced N2 peak amplitudes compared to normal controls for Go as well as NoGo task conditions. Control subjects showed significantly larger NoGo than Go N2 amplitudes at frontal regions, whereas alcoholics did not show any differences between task conditions at frontal regions. Standardized low resolution electromagnetic tomography analysis (sLORETA) indicated that alcoholics had significantly lower current density at the source than control subjects for the NoGo condition at bilateral anterior prefrontal regions, whereas the differences between groups during the Go trials were not statistically significant. Furthermore, NoGo current density across both groups revealed significantly more activation in bilateral anterior cingulate cortical (ACC) areas, with the maximum activation in the right cingulate regions. However, the magnitude of this difference was much less in alcoholics compared to control subjects. These findings suggest that alcoholics may have deficits in effortful processing during the motor response and its inhibition, suggestive of possible frontal lobe dysfunction.

Brain signatures of monetary loss and gain: outcome-related potentials in a single outcome gambling task

This study evaluates the event-related potential (ERP) components in a single outcome gambling task that involved monetary losses and gains. The participants were 50 healthy young volunteers (25 males and 25 females). The gambling task involved valence (loss and gain) and amount (50 cent and 10 cent) as outcomes. The outcome-related negativity (ORN/N2) and outcome-related positivity (ORP/P3) were analyzed and compared across conditions and gender. Monetary gain (compared to loss) and higher amount (50 cent compared to 10 cent) produced higher amplitudes and shorter latencies in both ORN and ORP components. Difference wave plots showed that earlier processing (200-400 ms) is dominated by the valence (loss/gain) while later processing (after 400 ms) is marked by the amount (50 cent/10 cent). Functional mapping using Low Resolution Electromagnetic Tomography (LORETA) indicated that the ORN separated the loss against gain in both genders, while the ORP activity distinguished the 50 cent against 10 cent in males. This study further strengthens the view that separate brain processes/circuitry may mediate loss and gain. Although there were no gender differences in behavioral and impulsivity scores, ORN and ORP measures for different task conditions had significant correlations with behavioral scores. This gambling paradigm may potentially offer valuable indicators to study outcome processing and impulsivity in normals as well as in clinical populations.

Spatial-anatomical mapping of NoGo-P3 in the offspring of alcoholics: evidence of cognitive and neural disinhibition as a risk for alcoholism

OBJECTIVE The concept of disinhibition as a behavioral and biological trait has been considered to be involved in the etiology of alcoholism and its co-existing disorders. The magnitude and functional mapping of event-related potential P3(00) components were analyzed, in order to examine the possible response inhibition deficits in the offspring of alcoholics. METHODS The P3 components were compared between 50 offspring of alcoholics (OA) and a matched normal control group (NC) using a visual Go/NoGo task. The low-resolution electromagnetic tomography (LORETA) was used to analyze the functional brain mapping between groups. RESULTS The results indicated that the OA group manifested decreased P3 amplitude during the NoGo but not the Go condition compared to the NC group. The voxel-by-voxel analysis in LORETA showed group differences at several brain regions including prefrontal areas during the processing of NoGo but not Go signals. CONCLUSIONS The decreased NoGo-P3 suggests that cognitive and neural disinhibition in offspring of alcoholics may serve as a neurocognitive index for a phenotypic marker in the development of alcoholism and related disorders. SIGNIFICANCE Dysfunctional neural and response inhibition in the offspring of alcoholics perhaps provides an endophenotypic marker of risk for the development of alcoholism and related disorders.

Theta oscillations during the processing of monetary loss and gain: A perspective on gender and impulsivity

Event-related oscillations (EROs) have proved to be very useful in the understanding of a variety of neurocognitive processes including reward/outcome processing. In the present study, theta power (4.0-7.0 Hz) following outcome stimuli in the time window of the N2-P3 complex (200-500 ms) was analyzed in healthy normals (20 males and 20 females) while performing a gambling task that involved monetary loss and gain. The main aim was to analyze outcome processing in terms of event-related theta power in the context of valence, amount, gender, and impulsivity. The S-transform was used for the signal processing of the ERO data in terms of time-frequency-power. Results from filtered waveforms showed a partially consistent phase-alignment of the increased theta activity corresponding to N2 and P3 components following the outcome stimuli. Gain conditions produced more theta power than loss conditions. While there was anterior involvement in both gain and loss, posterior activation was stronger during gain conditions than during loss conditions. Females exhibited posterior maxima during gain conditions while males had an anterior maxima during both loss and gain conditions. The current source density of theta activity in females involved larger areas with a bilateral frontal activity while males predominantly had a frontal midline activity. Theta power was significantly higher in females than males across all conditions. Low theta (4.0-5.5 Hz) predominantly contributed to the posterior activity during gain conditions. High theta (5.5-7.0 Hz) was more associated with impulsivity measures than low theta activity. These findings may offer valuable clues to understand outcome processing, impulsivity, and gender differences.

Dysfunctional reward processing in male alcoholics: An ERP study during a gambling task

OBJECTIVE A dysfunctional neural reward system has been shown to be associated with alcoholism. The current study aims to examine reward processing in male alcoholics by using event-related potentials (ERPs) as well as behavioral measures of impulsivity and risk-taking. METHODS Outcome-related negativity (ORN/N2) and positivity (ORP/P3) derived from a single outcome gambling task were analyzed using a mixed model procedure. Current density was compared across groups and outcomes using standardized low resolution electromagnetic tomography (sLORETA). Behavioral scores were also compared across groups. Correlations of ERP factors with behavioral and impulsivity factors were also analyzed. RESULTS Alcoholics showed significantly lower amplitude than controls during all outcome conditions for the ORP component and decreased amplitude during the loss conditions for the ORN component. Within conditions, gain produced higher amplitudes than loss conditions. Topographically, both groups had an anterior focus during loss conditions and posterior maxima during gain conditions, especially for the ORN component. Decreased ORP current density at cingulate gyrus and less negative ORN current density at sensory and motor areas characterized the alcoholics. Alcoholics had higher levels of impulsivity and risk-taking features than controls. CONCLUSIONS Deficient outcome/reward processing and increased impulsivity and risk-taking observed in alcoholics may be at least partly due to reward deficiency and/or dysfunctional reward circuitry in the brain, suggesting that alcoholism can be considered as part of the cluster of the reward deficiency syndrome (RDS).

Auditory P3 in Female Alcoholics

BACKGROUND The P3 (P300) has been considered to be a phenotypical marker of the risk for alcoholism. Although reductions in visual P3 in male and female alcoholics have been replicated, studies of auditory target P3 have been inconsistent. Our objective was to study the magnitude of auditory P3 reduction in female alcoholics and to establish the association between P3 reduction and alcoholism while taking into account comorbid depression and psychoactive drug dependence. The characteristics of P3 reduction were further examined by studying the reduction in family history-positive and -negative individuals. METHODS Auditory target P3s recorded from 61 scalp electrodes in female alcoholics (n = 71) were compared with P3s from female controls (n = 159) ranging in age from 18 to 50 years. The amplitudes and latencies were statistically analyzed, by using repeated-measures ANOVA, in six regional electrode arrays and at representative electrode sites, with age and comorbid depression as covariates. The effects of family density and clinical variables such as depression and drug dependence were also examined with correlation analysis. RESULTS Alcoholic women had significantly lower P3 amplitudes in all six regions and at midline electrode sites. The reductions were not associated with comorbid depression, as shown by low correlations and similar P3 amplitudes at Pz in female alcoholics with and without depression. The P3 amplitudes in women with a high family density were smaller than those in women with a low family density of alcohol dependence. Drug dependency did not influence P3 amplitude, as shown by similar responses in drug-dependent and non-drug-dependent alcoholic women. CONCLUSIONS These findings highlight the significance of P3 reductions associated with alcoholism in women, independently of comorbid depression. Family density effects further support the evidence that these findings are heritable. These results suggest that P3 can be considered as a phenotypical marker of vulnerability to alcoholism in women.