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 rewardrelated 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.

Reward Processing in Unipolar and Bipolar Depression: A Functional MRI Study

“…Given the differences between our paradigm and that of Chase et al (2013), the findings are not necessarily conflicting. However, in light of recent findings that indicate state-independent elevated striatal activity (Nusslock et al, 2014), but other researchers reporting results in the opposite direction (Trost et al, 2014), it seems to be important to separate the investigation of reward anticipation and reward outcome processing to gain a clearer picture in future studies.…”

“…However, not all available data support this notion. Compared with HCs, individuals with BD showed elevated VS activity during hypomania (O'Sullivan et al, 2011), no differences or elevated activity in euthymic states (Caseras et al, 2013;Nusslock et al, 2012), but activity was decreased in euthymic to mildly depressed patients (Trost et al, 2014). Chase et al (2013) is the first study that examined reward feedback in BD during depressive episodes and directly compared BD and UD.…”

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

“…So, during the RC, subjects were forced to overcome the tendency to acquire immediate reward (reject the previously conditioned reward stimuli) in order to reach the superordinate long-term goal. This situation therefore constituted a 'desire-reason dilemma' (Diekhof et al, 2012;Diekhof and Gruber, 2010;Trost et al, 2014). For more information, see also Supplementary Figure S1.…”

“…Psychophysiological interaction (PPI) (Diekhof and Gruber, 2010;Friston et al, 1997;Trost et al, 2014) was used to assess functional interactions of the ventral striatum with prefrontal brain regions, especially the anteroventral prefrontal cortex (avPFC), in the 'DRD' situation. Previous studies using the DRD paradigm in healthy subjects had shown a significant negative functional interaction between the ventral striatum and the avPFC in the dilemma situation (Diekhof and Gruber, 2010), while this negative functional interaction had been significantly impaired in bipolar patients in our latter study comparing bipolar patients with healthy controls (Trost et al, 2014).…”

“…In a recent functional magnetic resonance imaging (fMRI) study, we found that euthymic to mildly depressed bipolar I patients showed a reduced bottom-up responsiveness of the ventral striatum and a disturbed top-down control of the mesolimbic reward system by prefrontal brain regions while performing a specific reward paradigm, the 'Desire-Reason Dilemma' paradigm (DRD paradigm) (Trost et al, 2014). The DRD paradigm assesses the neural mechanisms underlying reward processing and active reward dismissal in favor of a long-term goal (Diekhof and Gruber, 2010).…”