Dataset Information

Response Inhibition and Binge Drinking During Transition to University: An fMRI Study.

ABSTRACT: Background:Binge Drinking (BD), a highly prevalent drinking pattern among youth, has been linked with anomalies in inhibitory control. However, it is still not well characterized whether the neural mechanisms involved in this process are compromised in binge drinkers (BDs). Furthermore, recent findings suggest that exerting inhibitory control to alcohol-related stimuli requires an increased effort in BDs, relative to controls, but the brain regions subserving these effects have also been scarcely investigated. Here we explored the impact of BD on the pattern of neural activity mediating response inhibition and its modulation by the motivational salience of stimuli (alcohol-related content). Methods:Sixty-seven (36 females) first-year university students, classified as BDs (n = 32) or controls (n = 35), underwent fMRI as they performed an alcohol-cued Go/NoGo task in which pictures of alcoholic or non-alcoholic beverages were presented as Go or NoGo stimuli. Results:During successful inhibition trials, BDs relative to controls showed greater activity in the bilateral inferior frontal gyrus (IFG), extending to the anterior insula, a brain region usually involved in response inhibition tasks, despite the lack of behavioral differences between groups. Moreover, BDs displayed increased activity in this region restricted to the right hemisphere when inhibiting a prepotent response to alcohol-related stimuli. Conclusions:The increased neural activity in the IFG/insula during response inhibition in BDs, in the absence of behavioral impairments, could reflect a compensatory mechanism. The findings suggest that response inhibition-related activity in the right IFG/insula is modulated by the motivational salience of stimuli and highlight the role of this brain region in suppressing responses to substance-associated cues.

SUBMITTER: Suarez-Suarez S

PROVIDER: S-EPMC7296115 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Response Inhibition and Binge Drinking During Transition to University: An fMRI Study.

Suárez-Suárez Samuel S Doallo Sonia S Pérez-García Jose Manuel JM Corral Montserrat M Rodríguez Holguín Socorro S Cadaveira Fernando F

Frontiers in psychiatry 20200609

<h4>Background</h4>Binge Drinking (BD), a highly prevalent drinking pattern among youth, has been linked with anomalies in inhibitory control. However, it is still not well characterized whether the neural mechanisms involved in this process are compromised in binge drinkers (BDs). Furthermore, recent findings suggest that exerting inhibitory control to alcohol-related stimuli requires an increased effort in BDs, relative to controls, but the brain regions subserving these effects have also been ...[more]

PMID: 32581896

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Project description:Disinhibition over drug use, enhanced salience of drug use and decreased salience of natural reinforcers are thought to play an important role substance dependence. Whether this is also true for pathological gambling is unclear. To understand the effects of affective stimuli on response inhibition in problem gamblers (PRGs), we designed an affective Go/Nogo to examine the interaction between response inhibition and salience attribution in 16 PRGs and 15 healthy controls (HCs).Four affective blocks were presented with Go trials containing neutral, gamble, positive or negative affective pictures. The No-Go trials in these blocks contained neutral pictures. Outcomes of interest included percentage of impulsive errors and mean reaction times in the different blocks. Brain activity related to No-Go trials was assessed to measure response inhibition in the various affective conditions and brain activity related to Go trials was assessed to measure salience attribution.PRGs made fewer errors during gamble and positive trials than HCs, but were slower during all trials types. Compared to HCs, PRGs activated the dorsolateral prefrontal cortex, anterior cingulate and ventral striatum to a greater extent while viewing gamble pictures. The dorsal lateral and inferior frontal cortex were more activated in PRGs than in HCs while viewing positive and negative pictures. During neutral inhibition, PRGs were slower but similar in accuracy to HCs, and showed more dorsolateral prefrontal and anterior cingulate cortex activity. In contrast, during gamble and positive pictures PRGs performed better than HCs, and showed lower activation of the dorsolateral and anterior cingulate cortex.This study shows that gambling-related stimuli are more salient for PRGs than for HCs. PRGs seem to rely on compensatory brain activity to achieve similar performance during neutral response inhibition. A gambling-related or positive context appears to facilitate response inhibition as indicated by lower brain activity and fewer behavioural errors in PRGs.

Project description:Cyclic AMP (cAMP)-dependent signaling is highly implicated in the pathophysiology of alcohol use disorder (AUD), with evidence supporting the efficacy of inhibiting the cAMP hydrolyzing enzyme phosphodiesterase 4 (PDE4) as a therapeutic strategy for drinking reduction. Off-target emetic effects associated with non-selective PDE4 inhibitors has prompted the development of selective PDE4 isozyme inhibitors for treating neuropsychiatric conditions. Herein, we examined the effect of a selective PDE4B inhibitor A33 (0-1.0 mg/kg) on alcohol drinking in both female and male mice from two genetically distinct C57BL/6 substrains. Under two different binge-drinking procedures, A33 pretreatment reduced alcohol intake in male and female mice of both substrains. In both drinking studies, there was no evidence for carry-over effects the next day; however, we did observe some sign of tolerance to A33's effect on alcohol intake upon repeated, intermittent, treatment (5 injections of 1.0 mg/kg, every other day). Pretreatment with 1.0 mg/kg of A33 augmented sucrose intake by C57BL/6NJ, but not C57BL/6J, mice. In mice with a prior history of A33 pretreatment during alcohol-drinking, A33 (1.0 mg/kg) did not alter spontaneous locomotor activity or basal motor coordination, nor did it alter alcohol's effects on motor activity, coordination or sedation. In a distinct cohort of alcohol-naïve mice, acute pretreatment with 1.0 mg/kg of A33 did not alter motor performance on a rotarod and reduced sensitivity to the acute intoxicating effects of alcohol. These data provide the first evidence that selective PDE4B inhibition is an effective strategy for reducing excessive alcohol intake in murine models of binge drinking, with minimal off-target effects. Despite reducing sensitivity to acute alcohol intoxication, PDE4B inhibition reduces binge alcohol drinking, without influencing behavioral sensitivity to alcohol in alcohol-experienced mice. Furthermore, A33 is equally effective in males and females and exerts a quantitatively similar reduction in alcohol intake in mice with a genetic predisposition for high versus moderate alcohol preference. Such findings further support the safety and potential clinical utility of targeting PDE4 for treating AUD.

Dataset Information

Response Inhibition and Binge Drinking During Transition to University: An fMRI Study.

Publications

Response Inhibition and Binge Drinking During Transition to University: An fMRI Study.

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