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Disrupted regulation of social exclusion in alcohol-dependence: an fMRI study.

ABSTRACT: Alcohol-dependence is associated with cognitive and biological alterations, and also with interpersonal impairments. Although overwhelming in clinical settings and involved in relapse, these social impairments have received little attention from researchers. Particularly, brain alterations related to social exclusion have not been explored in alcohol-dependence. Our primary purpose was to determine the neural correlates of social exclusion feelings in this population. In all, 44 participants (22 abstinent alcohol-dependent patients and 22 paired controls) played a virtual game ('cyberball') during fMRI recording. They were first included by other players, then excluded, and finally re-included. Brain areas involved in social exclusion were identified and the functional connectivity between these areas was explored using psycho-physiological interactions (PPI). Results showed that while both groups presented dorsal anterior cingulate cortex (dACC) activations during social exclusion, alcohol-dependent participants exhibited increased insula and reduced frontal activations (in ventrolateral prefrontal cortex) as compared with controls. Alcohol-dependence was also associated with persistent dACC and parahippocampal gyrus activations in re-inclusion. PPI analyses showed reduced frontocingulate connectivity during social exclusion in alcohol-dependence. Alcohol-dependence is thus linked with increased activation in areas eliciting social exclusion feelings (dACC-insula), and with impaired ability to inhibit these feelings (indexed by reduced frontal activations). Altered frontal regulation thus appears implied in the interpersonal alterations observed in alcohol-dependence, which seem reinforced by impaired frontocingulate connectivity. This first exploration of the neural correlates of interpersonal problems in alcohol-dependence could initiate the development of a social neuroscience of addictive states.

SUBMITTER: Maurage P

PROVIDER: S-EPMC3398714 | biostudies-other | 2012 Aug

REPOSITORIES: biostudies-other

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Project description:INTRODUCTION: With the progression of substance dependence, drug cue-related brain activation is thought to shift from motivational towards habit pathways. However, a direct association between cue-induced brain activation and dependence duration has not yet been shown. We therefore examined the relationship between alcohol cue-reactivity in the brain, cue-induced subjective craving and alcohol dependence duration and severity. Since alcohol dependence is highly comorbid with depression/anxiety, which may modulate brain responses to alcohol cues, we also examined the relation between comorbid depression/anxiety and cue-reactivity. METHODS: We compared 30 alcohol dependent patients with 15 healthy controls and 15 depression/anxiety patients during a visual alcohol cue-reactivity task using functional magnetic resonance imaging blood oxygenated level-dependent responses and subjective craving as outcomes. Within the alcohol dependent group we correlated cue-reactivity with alcohol dependence severity and duration, with cue-induced craving and with depression/anxiety levels. RESULTS: Alcohol dependent patients showed greater cue-reactivity in motivational brain pathways and stronger subjective craving than depression/anxiety patients and healthy controls. Depression/anxiety was not associated with cue-reactivity, but depression severity in alcohol dependent patients was positively associated with craving. Within alcohol dependence, longer duration of alcohol dependence was associated with stronger cue-related activation of the posterior putamen, a structure involved in habits, whereas higher alcohol dependence severity was associated with lower cue-reactivity in the anterior putamen, an area implicated in goal-directed behavior preceding habit formation. CONCLUSION: Cue-reactivity in alcohol dependence is not modulated by comorbid depression or anxiety. More importantly, the current data confirm the hypothesis of a ventral to dorsal striatal shift of learning processes with longer dependence duration, which could underlie increasingly habitual substance use with progressing substance dependence.

Project description:BackgroundOur previous work characterized altered cerebral activations during cognitive control in individuals with alcohol dependence (AD). A hallmark of cognitive control is the ability to anticipate changes and adjust behavior accordingly. Here, we employed a Bayesian model to describe trial-by-trial anticipation of the stop signal and modeled fMRI signals of conflict anticipation in a stop signal task. Our goal is to characterize the neural correlates of conflict anticipation and its relationship to response inhibition and alcohol consumption in AD.MethodsTwenty-four AD and 70 age and gender matched healthy control individuals (HC) participated in the study. fMRI data were pre-processed and modeled with SPM8. We modeled fMRI signals at trial onset with individual events parametrically modulated by estimated probability of the stop signal, p(Stop), and compared regional responses to conflict anticipation between AD and HC. To address the link to response inhibition, we regressed whole-brain responses to conflict anticipation against the stop signal reaction time (SSRT).ResultsCompared to HC (54/70), fewer AD (11/24) showed a significant sequential effect - a correlation between p(Stop) and RT during go trials - and the magnitude of sequential effect is diminished, suggesting a deficit in proactive control. Parametric analyses showed decreased learning rate and over-estimated prior mean of the stop signal in AD. In fMRI, both HC and AD responded to p(Stop) in bilateral inferior parietal cortex and anterior pre-supplementary motor area, although the magnitude of response increased in AD. In contrast, HC but not AD showed deactivation of the perigenual anterior cingulate cortex (pgACC). Furthermore, deactivation of the pgACC to increasing p(Stop) is positively correlated with the SSRT in HC but not AD. Recent alcohol consumption is correlated with increased activation of the thalamus and cerebellum in AD during conflict anticipation.ConclusionsThe current results highlight altered proactive control that may serve as an additional behavioral and neural marker of alcohol dependence.

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Disrupted regulation of social exclusion in alcohol-dependence: an fMRI study.

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