Waiting to win: elevated striatal and orbitofrontal cortical activity during reward anticipation in euthymic bipolar disorder adults

Abstract

Objective Bipolar disorder may be characterized by a hypersensitivity to reward-relevant stimuli, potentially underlying the emotional lability and dysregulation that characterizes the illness. In parallel, research highlights the predominant role of striatal and orbitofrontal cortical (OFC) regions in reward-processing and approach-related affect. We aimed to examine whether bipolar disorder, relative to healthy, participants displayed elevated activity in these regions during reward processing. Methods Twenty-one euthymic bipolar I disorder and 20 healthy control participants with no lifetime history of psychiatric disorder underwent functional magnetic resonance imaging (fMRI) scanning during a card-guessing paradigm designed to examine reward-related brain function to anticipation and receipt of monetary reward and loss. Data were collected using a 3T Siemens Trio scanner. Results Region-of-interest analyses revealed that bipolar disorder participants displayed greater ventral striatal and right-sided orbitofrontal [Brodmann area (BA) 11] activity during anticipation, but not outcome, of monetary reward, relative to healthy controls (p < 0.05, corrected). Wholebrain analyses indicated that bipolar disorder, relative to healthy, participants also displayed elevated left-lateral OFC activity (BA 47) activity during reward anticipation (p < 0.05, corrected). Conclusions Elevated ventral striatal and OFC activity during reward anticipation may represent a neural mechanism for predisposition to expansive mood and hypo/mania in response to reward-relevant cues that characterizes bipolar disorder. Our findings contrast with research reporting blunted activity in the ventral striatum during reward processing in unipolar depressed individuals, relative to healthy controls. Examination of reward-related neural activity in bipolar disorder is a promising research focus to facilitate identification of biological markers of the illness.

Common and Dissociable Dysfunction of the Reward System in Bipolar and Unipolar Depression

“…In contrast, several studies in non-depressed subjects with bipolar disorder have found evidence of reward system hyper-responsivity. Elevated reward system responses have been reported in both manic (Abler et al, 2008) and euthymic bipolar patients (Nusslock et al, 2012;Caseras et al, 2013). However, only one study to our knowledge has examined reward-related signaling in bipolar depression: Chase et al (2013) who did not find differences in ventral striatum prediction error responses between controls and subjects with bipolar or unipolar depression.…”

“…However, prior research suggests that bipolar patients studied during mania or euthymic states may have enhanced reward responses (Abler et al, 2008;Nusslock et al, 2012;Caseras et al, 2013). Although speculative, it is possible that patients with bipolar disorder may have tonically elevated reward system activation and connectivity, which is dimensionally blunted in depressive episodes.…”

Investigating the Impact of a Genome-Wide Supported Bipolar Risk Variant of MAD1L1 on the Human Reward System

“…Recent fMRI studies showed alterations in reward-related striatal and cortical brain activations, state-dependent, but also during euthymia (Abler et al, 2008;Caseras et al, 2013;Nusslock et al, 2012;Trost et al, 2014;Whitton et al, 2015). A number of studies have reported elevated striatal activations in response to rewarding stimuli in hypomanic individuals (O'Sullivan et al, 2011), euthymic (Mason et al, 2014;Nusslock et al, 2012) and manic (Abler et al, 2008) bipolar patients. However, other studies in bipolar patients have shown a reduced reward responsiveness challenging the hypothesis of a general reward hypersensitivity model of bipolar disorder.…”

Hypoactivation of the Ventral and Dorsal Striatum During Reward and Loss Anticipation in Antipsychotic and Mood Stabilizer-Naive Bipolar Disorder

“…Studies of medicated patients with BD have reported increased activity in the ventral striatum (VS) during reward and affective processing (Lawrence et al, 2004;Nusslock et al, 2012;Caseras et al, 2013), and this has been interpreted as reflecting increased reward sensitivity and more generally a 'reward hypersensitivity model for BD' (Caseras et al, 2013). However, nascent data suggest ameliorative effects of antipsychotic and mood-stabilizing medications on neural activity within limbic circuits, making accurate interpretation of data from medicated individuals difficult (Haldane et al, 2008;Phillips et al, 2008;Passarotti et al, 2011).…”