Alcoholism is a disinhibitory disorder: neurophysiological evidence from a Go/No-Go task
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).
References (114)
CNS recovery from cocaine, cocaine and alcohol, or opioid dependence: a P300 study
Clinical Neurophysiology
(2001)- et al.
P300 decrements in teenagers with conduct problems: implications for substance abuse risk and brain development
Biological Psychiatry
(1999) - et al.
Subtypes of family history and conduct disorder: effects on P300 during the stroop test
Neuropsychopharmacology
(1999) - et al.
Quantitative trait loci analysis of human event-related brain potentials: P3 voltage
Electroencephalography and Clinical Neurophysiology
(1998) - et al.
Multicenter P300 brain mapping of impaired attention to cues in hyperkinetic children
Journal of the American Academy of Child and Adolescent Psychiatry
(2002) - et al.
Dissociable contributions of prefrontal and parietal cortices to response selection
Neuroimage
(2002) - et al.
Evidence for a mechanistic model of cognitive control
Clinical Neuroscience Research
(2001) - et al.
Neuroelectric correlates of response production and inhibition in individuals at risk to develop alcoholism
Biological Psychiatry
(1997) - et al.
Brain imaging of the central executive component of working memory
Neuroscience and Biobehavioral Reviews
(2002) Neural correlates of attention and arousal: insights from electrophysiology, functional neuroimaging and psychopharmacology
Progress in Neurobiology
(1998)
The effect of preceding context on inhibition: an event-related fMRI study
Neuroimage
Effects of attention and stimulus probability on ERPs in a Go/Nogo task
Biological Psychology
ERP components in Go/Nogo tasks and their relation to inhibition
Acta Psychologica
Late ERP components in visual and auditory Go/Nogo tasks
Electroencephalography and Clinical Neurophysiology
Electrophysiological signs of reduced prefrontal response control in schizophrenic patients
Psychiatry Research
“Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician
Journal of Psychiatric Research
Dissociable executive functions in the dynamic control of behavior: inhibition, error detection, and correction
Neuroimage
Auditory P3a assessment of male alcoholics
Biological Psychiatry
Auditory P3a deficits in male subjects at high risk for alcoholism
Biological Psychiatry
An on-line transformation of EEG scalp potentials into orthogonal source derivations
Electroencephalography and Clinical Neurophysiology
Effects of practice on the P300 in a Go/NoGo task
Electroencephalography and Clinical Neurophysiology
Relation of a negative ERP component to response inhibition in a Go/No-go task
Electroencephalography and Clinical Neurophysiology
Executive control deficit in depression: event-related potentials in a Go/Nogo task
Psychiatry Research
The role of brain oscillations as functional correlates of cognitive systems: a study of frontal inhibitory control in alcoholism
International Journal of Psychophysiology
Motor performance and sensory-evoked potentials
Electroencephalography and Clinical Neurophysiology
Functional anatomy of GO/NO-GO discrimination and response selection—a PET study in man
Brain Research
Reduced P300 responses in criminal psychopaths during a visual oddball task
Biolical Psychiatry
An event-related potential investigation of response inhibition in schizophrenia and psychopathy
Biolical Psychiatry
N2, P3 and the lateralized readiness potential in a nogo task involving selective response priming
Electroencephalography and Clinical Neurophysiology
P300 assessment of opiate and cocaine users: effects of detoxification and buprenorphine treatment
Biological Psychiatry
Attention shifts and anticipatory mechanisms in hyperactive children: an ERP study using the Posner paradigm
Biological Psychiatry
ERPs to stimuli requiring response production and inhibition: effects of age, probability and visual noise
Electroencephalography and Clinical Neurophysiology
Reorganization of frontal systems used by alcoholics for spatial working memory: an fMRI study
Neuroimage
Age-related changes in auditory event-related potentials
Electroencephalography and Clinical Neurophysiology
ERPs to response production and inhibition
Electroencephalography and Clinical Neurophysiology
Clinical application of the P3 component of event-related potentials. I. Normal aging
Electroencephalography and Clinical Neurophysiology
Inhibitory control in children with attention-deficit/hyperactivity disorder: event-related potentials identify the processing component and timing of an impaired right-frontal response-inhibition mechanism
Biological Psychiatry
Event-related potentials in individuals at risk for alcoholism
Alcohol
Event-related brain potentials to high incentive stimuli in abstinent alcoholics
Alcohol
Linkage and linkage disequilibrium mapping of ERP and EEG phenotypes
Biological Psychology
Attentional networks
Trends in Neuroscience
A functional MRI study of visual oddball: evidence for frontoparietal dysfunction in subjects at risk for alcoholism
Neuroimage
Mapping P300 waves onto inhibition: Go/No-Go discrimination
Electroencephalography and Clinical Neurophysiology
Inhibitory dysfunction in hyperactive boys
Behavioural Brain Research
Event-related dynamics of the gamma-band oscillation in the human brain: information processing during a GO/NOGO hand movement task
Neuroscience Research
The scalp topography of potentials in auditory and visual Go/NoGo tasks
Electroencephalography and Clinical Neurophysiology
A bootstrap method to compare the shapes of two scalp fields
Electroencephalography and Clinical Neurophysiology
Heritability of event-related brain potentials in families with a history of alcoholism
American Journal of Medical Genetics
Genetic correlation between the P300 event-related brain potential and the EEG power spectrum
Behavior Genetics
Behavioral inhibition, sustained attention, and executive functions: constructing a unifying theory of ADHD
Psychological Bulletin
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2021, Clinical NeurophysiologyCitation Excerpt :Lower N2 amplitudes in both Go and NoGo trials in AUD patients compared to controls have been found (e.g., Pandey et al., 2012). While NoGo-N2 components were furthermore shown to be attenuated in heavy compared to light drinkers (Oddy and Barry, 2009), other studies were unable to find such group differences (Petit et al., 2014, Stein et al., 2018, Kamarajan et al., 2005a). However, in subjects with strong craving, the conflict reflected in the NoGo-N2 was shown to be enhanced when inhibition had to be executed in alcohol-related contexts (Stein et al., 2018).
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Present address: Department of Psychology, New York University, New York, NY 10003, USA.