Elsevier

Biological Psychology

Volume 69, Issue 3, July 2005, Pages 353-373
Biological Psychology

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

https://doi.org/10.1016/j.biopsycho.2004.08.004Get rights and content

Abstract

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.

Introduction

The event-related potentials (ERPs) using Go/No-Go tasks have been widely examined to elucidate the possible neural correlates of response activation and inhibition in normals as well as in clinical groups (Jodo and Inoue, 1990, Falkenstein et al., 1995, Falkenstein et al., 1999, Shibata et al., 1999, Weisbrod et al., 2000, Kaiser et al., 2003). These tasks require the subjects to respond to one type of stimuli (Go condition), but to withhold the response to the other (No-Go condition). In the No-Go condition, two major ERP components have been identified as the markers for response inhibition: first, the N2, a negative deflection with a frontocentral maximum around 200–300 ms, and second, referred to as “No-Go P3”, an augmented positive-going peak usually peaking between 300 and 600 ms (Pfefferbaum et al., 1985, Eimer, 1993, Jodo and Inoue, 1990, Jodo and Kayama, 1992, Kopp et al., 1996). However, the N2 and P3 components during the No-Go condition may represent different processing of response inhibition and hence the dysfunction in either or both of these components in different mental disorders may suggest the deficiency of inhibitory control (Kaiser et al., 2003).

Response inhibition requires the activation of the executive system of the frontal lobes (Barkley, 1997, Weisbrod et al., 2000, Kaiser et al., 2003). On the other hand, the neural basis of this executive system is thought to be a distributed network involving the prefrontal areas and anterior cingulate gyrus (Posner and DiGirolamo, 1998, Smith and Jonides, 1999). However, theories based on the findings of lesion studies stressed the importance of the orbitofrontal cortex in inhibitory control (i.e., Mishkin, 1964, Fuster, 1989). Consistent with the distributed activations that underlie most of the cognitive processes, neuroimaging studies have revealed cerebral activation beyond ventral frontal regions during response inhibition (Brown et al., 1999, Garavan et al., 1999, Garavan et al., 2002). The distributed network thought to underlie inhibitory control, as observed with neuroimaging studies, includes the dorsal and ventral prefrontal regions (Kawashima et al., 1996, Tsujimoto et al., 1997, Smith et al., 1998, Konishi et al., 1998, Watanabe et al., 2002), anterior cingulate cortex (Casey et al., 1997, Liddle et al., 2001, Menon et al., 2001, Garavan et al., 2002, Durston et al., 2002), premotor and supplementary motor areas (Ullsperger and von Cramon, 2001, Garavan et al., 2002, Sylvester et al., 2003), and parietal regions (Garavan et al., 1999, Watanabe et al., 2002, Durston et al., 2002).

A robust finding in ERP studies on alcoholism is that alcoholics as well as individuals at high risk to develop alcoholism have been shown to have low P3 amplitude in various task paradigms (Begleiter et al., 1984, Porjesz et al., 1987, Porjesz and Begleiter, 1990, Porjesz and Begleiter, 1991, Porjesz and Begleiter, 1996, Rodriguez Holguin et al., 1999, Hada et al., 2000, Prabhu et al., 2001, Cohen et al., 2002, Suresh et al., 2003). In Go/No-Go tasks, the anteriorly distributed No-Go P3 potential has a markedly reduced amplitude in alcoholic subjects as well as in high-risk individuals, indicating impaired inhibitory control in these individuals (Pfefferbaum et al., 1991, Cohen et al., 1997a, Cohen et al., 1997b). However, the deficits in inhibitory control have been reported in a variety of behavioral disorders, which share disinhibitory psychopathology in common, including OCD and Tourette syndrome (Schall et al., 1996, Johannes et al., 2001, Johannes et al., 2003), ADHD (Frank et al., 1998, Rubia et al., 1998, Pliszka et al., 2000, Brandeis et al., 2002), ASP and conduct disorder (Bauer and Hesselbrock, 1999a, Bauer and Hesselbrock, 1999b, Kiehl et al., 1999, Kiehl et al., 2000), schizophrenia (Weisbrod et al., 2000, Fallgatter and Muller, 2001), and drug use (Kouri et al., 1996, Bauer, 2001, Kaufman et al., 2003). Based on the patterns of comorbidity, it was suggested that the common psychiatric and substance use syndromes may be divisible into two broad groups of internalizing and externalizing disorder (Kendler et al., 2003). Despite the fact that the addictive disorders inclusive of alcoholism would also involve very specific aspects of disinhibition such as drug incentive salience, drug expectation or craving, and compulsive drug intake, the electrophysiological markers of response inhibition specific to alcoholism, as distinct from other disinhibitory disorders, are poorly understood. Nevertheless, it is important to determine not only the magnitude but also the topographic distribution of averaged brain potentials as well as the estimated surface Laplacian in alcoholism, as this might explain the cortical dynamics and networks during cortical processing.

In the present study, along with ERPs, we have therefore attempted to examine the spatial distribution of current source density (CSD) which may give distinct topographic features specific to alcoholism during response inhibition. The CSD is a method which applies an estimate of surface Laplacian and can provide differential topographic features of cortical surface potentials devoid of volume conduction effects (Nunez, 1995, Srinivasan et al., 1998, Wang and Begleiter, 1999). Although the CSD has successfully differentiated alcoholics and controls in terms of topographic differences (Hada et al., 2000, Hada et al., 2001), this method has not been studied in a Go/No-Go paradigm in alcoholics. The objective of the present study was to examine the ERP as well as CSD correlates of response inhibition in alcoholics and control subjects using a Go/No-Go task. By comparing the magnitude, spatial and temporal characteristics of these measures in alcoholic subjects and healthy controls, it may be possible to elucidate the specific neuro-cognitive abnormalities related to response inhibition in alcoholics. Further, recent advances in understanding the brain mechanisms involved in inhibitory control, impulsivity, motivation, reward, and decision-making might permit a discussion of neural circuitry underlying the pathology of addiction.

Section snippets

Subjects

The demographic and clinical characteristics of the sample are presented in Table 1. A sample of 30 alcoholics (16 males, 14 females) with an age range of 19–42 years and 30 gender-matched healthy controls aged between 18 and 35 years were selected. Control subjects were recruited through newspaper advertisements and notices. The alcoholic group comprised diagnosed alcoholic patients from the de-addiction centers of the hospitals in New York, primarily from Kings County Hospital Center at

Demographic and behavioral data

The behavioral and cognitive performance scores between control and alcoholic subjects are shown in Table 2. The alcoholics were significantly older than the controls (t = 7.832; P = 0.000), and age as a variable has been included in the MANCOVA model for group comparison. Although the control subjects were relatively more educated than the alcoholics (t = 4.147; P = 0.000), education was not included in the MANCOVA model, as this variable has not been consistently shown to affect the

Discussion

The amplitude and topographic features of ERPs and CSD were assessed in alcoholic subjects and in healthy controls using a visual Go/No-Go task. The main objective of this study was to examine P3 characteristics between alcoholics and controls during response inhibition (No-Go condition) as well as response activation (Go condition). The results yielded four important findings: (1) alcoholics manifested significantly lower P3 amplitudes during the No-Go as well as Go conditions, implying

Acknowledgments

The authors are grateful to the valuable assistance of Aquanette Sass, Aleksey Dumer, Lakshmi Krishnamurthy, Glenn Murawski, Tracy Crippen, Carlene Haynes, and Joyce Alonzia. This study was supported by the NIH grant # 5 RO1 AA02686 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA).

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    Present address: Department of Psychology, New York University, New York, NY 10003, USA.

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