Yongqiang Tang

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.

Association of single nucleotide polymorphisms in a glutamate receptor gene (GRM8) with theta power of event-related oscillations and alcohol dependence†‡

Evidence suggests the P3 amplitude of the event‐related potential and its underlying superimposed event‐related oscillations (EROs), primarily in the theta (4–5 Hz) and delta (1–3 Hz) frequencies, as endophenotypes for the risk of alcoholism and other disinhibitory disorders. Major neurochemical substrates contributing to theta and delta rhythms and P3 involve strong GABAergic, cholinergic and glutamatergic system interactions. The aim of this study was to test the potential associations between single nucleotide polymorphisms (SNPs) in glutamate receptor genes and ERO quantitative traits. GRM8 was selected because it maps at chromosome 7q31.3–q32.1 under the peak region where we previously identified significant linkage (peak LOD = 3.5) using a genome‐wide linkage scan of the same phenotype (event‐related theta band for the target visual stimuli). Neural activities recorded from scalp electrodes during a visual oddball task in which rare target elicited P3s were analyzed in a subset of the Collaborative Study on the Genetics of Alcoholism (COGA) sample comprising 1,049 Caucasian subjects from 209 families (with 472 DSM‐IV alcohol dependent individuals). The family‐based association test (FBAT) detected significant association (P < 0.05) with multiple SNPs in the GRM8 gene and event‐related theta power to target visual stimuli, and also with alcohol dependence, even after correction for multiple comparisons by false discovery rate (FDR). Our results suggest that variation in GRM8 may be involved in modulating event‐related theta oscillations during information processing and also in vulnerability to alcoholism. These findings underscore the utility of electrophysiology and the endophenotype approach in the genetic study of psychiatric disorders.

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.

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.

Single-Nucleotide Polymorphisms in Corticotropin Releasing Hormone Receptor 1 Gene (CRHR1) Are Associated With Quantitative Trait of Event-Related Potential and Alcohol Dependence

BACKGROUND Endophenotypes reflect more proximal effects of genes than diagnostic categories, hence providing a more powerful strategy in searching for genes involved in complex psychiatric disorders. There is strong evidence suggesting the P3 amplitude of the event-related potential (ERP) as an endophenotype for the risk of alcoholism and other disinhibitory disorders. Recent studies demonstrated a crucial role of corticotropin releasing hormone receptor 1 (CRHR1) in the environmental stress response and ethanol self-administration in animal models. The aim of the present study was to test the potential associations between single-nucleotide polymorphisms (SNPs) in the CRHR1 gene and the quantitative trait, P3 amplitude during the processing of visual target signals in an oddball paradigm, as well as alcohol dependence diagnosis. METHODS We analyzed a sample from the Collaborative Study on the Genetics of Alcoholism (COGA) comprising 1049 Caucasian subjects from 209 families (including 472 alcohol-dependent individuals). Quantitative transmission disequilibrium test (QTDT) and family-based association test (FBAT) were used to test the association, and false discovery rate (FDR) was applied to correct for multiple comparisons. RESULTS Significant associations (p < 0.05) were found between the P3 amplitude and alcohol dependence with multiple SNPs in the CRHR1 gene. CONCLUSIONS Our results suggest that CRHR1 may be involved in modulating the P3 component of the ERP during information processing and in vulnerability to alcoholism. These findings underscore the utility of electrophysiology and the endophenotype approach in the genetic study of psychiatric disorders.

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).

Heritability of EEG coherence in a large sib-pair population.

The additive genetic heritability of bipolar EEG coherence in a sample of 305 non-twin sibships comprising 690 individuals (age range 7-65) was estimated. Heritabilities were examined in 6 frequency bands for each of 15 coherence pairs, both interhemispheric and intrahemispheric. The heritabilities of the bipolar EEG coherence ranged from 0.22 to 0.63 in 79 of the 90 phenotypes which had coherences high enough to provide meaningful values for the estimation of heritability. Heritabilities were greatest in the low and high alpha frequency bands, while theta and beta bands had comparable heritabilities. Coherences themselves were greatest in the low and high alpha frequency bands, while theta coherences were somewhat larger than beta. Higher heritability values were not associated with higher coherences. The examination of bivariate genetic correlations suggests that there is a difference between theta and alpha bands in genetic control of interhemispheric coherence.