Neural correlates of impulsivity in bipolar disorder: A systematic review and clinical implications

Abstract

Impulsivity is a common feature of bipolar disorder (BD) with ramifications for functional impairment and premature mortality. This PRISMA-guided systematic review aims to integrate findings on the neurocircuitry associated with impulsivity in BD. We searched for functional neuroimaging studies that examined rapid-response impulsivity and choice impulsivity using the Go/No-Go Task, Stop-Signal Task, and Delay Discounting Task. Findings from 33 studies were synthesized with an emphasis on the effect of mood state of the sample and affective salience of the task. Results suggest trait-like brain activation abnormalities in regions implicated in impulsivity that persist across mood states. During rapid-response inhibition, BD exhibit under-activation of key frontal, insular, parietal, cingulate, and thalamic regions, but over-activation of these regions when the task involves emotional stimuli. Delay discounting tasks with functional neuroimaging in BD are lacking, but hyperactivity of orbitofrontal and striatal regions associated with reward hypersensitivity may be related to difficulty delaying gratification. We propose a working model of neurocircuitry dysfunction underlying behavioral impulsivity in BD. Clinical implications and future directions are discussed.

Keywords: Choice impulsivity; Delay discounting; Functional neuroimaging; Go/no-go; Inhibition; Neurocircuitry; Rapid-response impulsivity; Stop-signal task.

Fig. 1.

PRISMA flow diagram for study selection.

Fig. 2.

Proposed model of key regions in disrupted neural circuits contributing to impulsivity in bipolar disorder (BD) based on findings from task-based functional magnetic resonance imaging studies (see Table 1 and 2). In rapid-response impulsivity, key regions involved in refraining from action initiation resemble those of the executive control network and include dorsolateral prefrontal cortex, inferior frontal gyrus, posterior parietal cortex, and anterior insula. Key regions involved in stopping an ongoing action include the inferior frontal gyrus, anterior insula, pre-supplementary motor area, cingulate cortex, subthalamic nucleus, and thalamus. The circuit involved in refraining from action initiation is largely underactive in BD compared with healthy controls, but becomes overactivated when affective stimuli are presented. We postulate this pattern to also be evident for the neurocircuitry involved in stopping an ongoing action, although this needs to be verified by studies using affective stimuli in tasks of stopping an ongoing action (noted with a question mark). Over-activation to affective stimuli may reflect a “compensatory” mechanism in which more effort is required to engage brain regions responsible for action inhibition in the context of affective stimuli due to hypersensitivity in affective contexts. These functional neuroimaging abnormalities are generally present without associated performance deficits and evident across mood states. Decisional choice impulsivity in BD is thought to be associated with hyperactivation in the frontostriatal reward network involving the medial orbital frontal cortex and ventral striatum (including nucleus accumbens) during reward anticipation and reward receipt. Over-activation in this network may reflect difficulty in prefrontal control systems to modulate reward sensitivity resulting in reward hypersensitivity, which may drive BD individuals to seek reward as soon as possible despite the availability of a later larger reward. Not all connections among regions are provided and not all regions involved in each type of impulsivity is shown.