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Disturbed anterior prefrontal control of the mesolimbic reward system and increased impulsivity in bipolar disorder.

ABSTRACT: Bipolar disorder (BD) is characterized by recurrent mood episodes ranging from severe depression to acute full-blown mania. Both states of this severe psychiatric disorder have been associated with alterations of reward processing in the brain. Here, we present results of a functional magnetic resonance imaging (fMRI) study on the neural correlates and functional interactions underlying reward gain processing and reward dismissal in favor of a long-term goal in bipolar patients. Sixteen medicated patients diagnosed with bipolar I disorder, euthymic to mildly depressed, and sixteen matched healthy controls performed the 'desire-reason dilemma' (DRD) paradigm demanding rejection of priorly conditioned reward stimuli to successfully pursue a superordinate goal. Both groups exhibited significant activations in reward-related brain regions, particularly in the mesolimbic reward system. However, bipolar patients showed reduced neural responses of the ventral striatum (vStr) when exploiting a reward stimulus, and exhibited a decreased suppression of the reward-related activation of the mesolimbic reward system while having to reject immediate reward in favor of the long-term goal. Further, functional interaction between the anteroventral prefrontal cortex and the vStr in the 'DRD' was significantly impaired in the bipolar group. These findings provide evidence for a reduced responsivity of the vStr to reward stimuli in BD, possibly related to clinical features like anhedonia. The disturbed top-down control of mesolimbic reward signals by prefrontal brain regions in BD can be interpreted in terms of a disease-related enhanced impulsivity, a trait marker of BD.

SUBMITTER: Trost S

PROVIDER: S-EPMC4059900 | biostudies-other | 2014 Jul

REPOSITORIES: biostudies-other

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Disturbed anterior prefrontal control of the mesolimbic reward system and increased impulsivity in bipolar disorder.

Trost Sarah S Diekhof Esther Kristina EK Zvonik Kerstin K Lewandowski Mirjana M Usher Juliana J Keil Maria M Zilles David D Falkai Peter P Dechent Peter P Gruber Oliver O

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20140218 8

Bipolar disorder (BD) is characterized by recurrent mood episodes ranging from severe depression to acute full-blown mania. Both states of this severe psychiatric disorder have been associated with alterations of reward processing in the brain. Here, we present results of a functional magnetic resonance imaging (fMRI) study on the neural correlates and functional interactions underlying reward gain processing and reward dismissal in favor of a long-term goal in bipolar patients. Sixteen medicate ...[more]

PMID: 24535101

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Project description:Bipolar disorder is characterized by impaired decision-making captured in impulsivity and risk-taking. We sought to determine whether this is driven by a failure to effectively weight the lower-order goal of obtaining a strongly desired reward in relation to higher-order goals, and how this relates to trait impulsivity and risk-taking. We hypothesized that in bipolar disorder the weighting of valuation signals converging on ventromedial prefrontal cortex are more heavily weighted towards ventral striatum inputs (lower-order), with less weighting of dorsolateral prefrontal cortex inputs (higher-order). Twenty euthymic patients with bipolar disorder not in receipt of antipsychotic medication and 20 case-matched controls performed a roulette task during functional magnetic resonance imaging. Activity in response to high-probability ('safe') and low-probability ('risky') prospects was measured during both anticipation, and outcome. In control subjects, anticipatory and outcome-locked activity in dorsolateral prefrontal cortex was greater for safe than risky reward prospects. The bipolar disorder group showed the opposite pattern with preferential response to risky rewards. This group also showed increased anticipatory and outcome-locked activity in ventral striatum in response to rewards. In control subjects, however, ventromedial prefrontal activation was positively associated with both ventral striatum and dorsolateral prefrontal activity; patients evidenced a strong positive association with ventral striatum, but a negative association with dorsolateral prefrontal cortex. Response to high-probability rewards in dorsolateral prefrontal cortex was inversely associated with trait impulsivity and risk-taking in the bipolar disorder group. Our findings suggest that clinically impulsive and risky decision-making are related to subjective valuation that is biased towards lower-order preference, with diminished integration of higher-order goals. The findings extend a functional neuroanatomical account of disorders characterized by clinically impulsive decision-making, and provide targets for evaluating interventions that foster self-control.

Project description:Internet Gaming Disorder (IGD) has been considered a potential behavioral or non-substance addiction that requires further investigation. Recognition of the commonalities between IGD and Substance Use disorders (SUD) would be of great help to better understand the basic mechanisms of addictive behaviors and excessive Internet gaming. However, little research has targeted a straightforward contrast between IGD and SUD on neuropsychological aspects. The present study thus aimed to explore the associations of reward processing and inhibitory control with IGD and nicotine dependence (ND) in young adults. Fifty-eight IGD and 53 ND individuals, as well as 57 age- and gender-matched healthy controls, were assessed with a series of measurements including the Delay-discounting Test (DDT), Probability Discounting Test (PDT), the Stroop Color-Word Task, a revised Go/No Go Task, and the Barratt Impulsiveness Scale (BIS-11). Multivariate analysis of variance (mANOVA) models revealed that both IGD and ND groups scored higher than healthy controls on the BIS-11 attentional, motor, and non-planning impulsiveness (Cohen's d = 0.41-1.75). Higher degrees of delay discounting on the DDT were also found in IGD and ND groups compared to healthy controls (Cohen's d = 0.53-0.69). Although IGD group did not differ from healthy controls on the PDT, ND group had a lower degree of probability discounting than healthy controls (Cohen's d = 0.55), suggesting a reduction in risk aversion. Furthermore, ND subjects showed a lower correct accuracy in the incongruent trials of the Stroop task than healthy controls (Cohen's d = 0.61). On the Go/No Go task, both IGD and ND groups had a lower correct accuracy in the No-Go trials than healthy controls (Cohen's d = 1.35-1.50), indicating compromised response inhibition. These findings suggested that IGD was linked to both anomalous reward discounting and dysfunctional inhibitory control, which was comparable with one typical SUD category (i.e., ND). This study might promote a better understanding of the pathogenesis of IGD as a potential addictive disorder similar to SUD.

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Disturbed anterior prefrontal control of the mesolimbic reward system and increased impulsivity in bipolar disorder.

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Disturbed anterior prefrontal control of the mesolimbic reward system and increased impulsivity in bipolar disorder.

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