Left ventrolateral prefrontal cortical activity during reward expectancy predicts mania risk up to one year post scan.

INTRODUCTION: Identification of neural markers associated with risk for manic symptoms is an important challenge for neuropsychiatric research. Previous work has highlighted the association between predisposition for mania/hypomania and elevated reward sensitivity. Elevated activity in the left ventrolateral prefrontal cortex (L vlPFC) during reward expectancy (RE) is associated with measures predictive of risk for manic/hypomanic symptoms. However, no studies have examined this relationship longitudinally. The goal of this study was to identify a neural marker associated with longitudinal risk for manic/hypomanic symptoms. METHODS: We used a card guessing functional magnetic resonance imaging (fMRI) paradigm to examine RE-related L vlPFC activity. One hundred and three young adults who were either healthy or experiencing psychological distress completed a single baseline fMRI scan and self-report measures of manic/hypomanic symptoms. Self-report measures were repeated up to two follow up visits over one year. RESULTS: We identified a significant positive relationship between baseline RE-related L vlPFC activity and MOODS Manic Domain scores up to one-year post scan. This relationship was specific to manic symptoms and was not present for MOODS depression-related domains. LIMITATIONS: This study was not designed to predict conversion to bipolar disorder, but rather the more proximal construct of lifetime risk for mania/hypomania. CONCLUSIONS: RE-related L vlPFC activity may serve as an important marker of risk for future manic/hypomanic symptoms and may also be a potential target for intervention.

The impact of targeted cathodal transcranial direct current stimulation on reward circuitry and affect in Bipolar Disorder.

Bipolar Disorder is costly and debilitating, and many treatments have side effects. Transcranial Direct Current Stimulation (tDCS) is a well-tolerated neuromodulation technique that may be a useful treatment for Bipolar Disorder if targeted to neural regions implicated in the disorder. One potential region is the left ventrolateral prefrontal cortex (vlPFC), which shows abnormally elevated activity during reward expectancy in individuals with Bipolar Disorder. We used a counterbalanced repeated measures design to assess the impact of cathodal (inhibitory) tDCS over the left vlPFC on reward circuitry activity, functional connectivity, and affect in adults with Bipolar Disorder, as a step toward developing novel interventions for individuals with the disorder. -1mA cathodal tDCS was administered over the left vlPFC versus a control region, left somatosensory cortex, concurrently with neuroimaging. Affect was assessed pre and post scan in remitted Bipolar Disorder (n = 27) and age/gender-matched healthy (n = 31) adults. Relative to cathodal tDCS over the left somatosensory cortex, cathodal tDCS over the left vlPFC lowered reward expectancy-related left ventral striatal activity (F(1,51) = 9.61, p = 0.003), and was associated with lower negative affect post scan, controlling for pre-scan negative affect, (F(1,49) = 5.57, p = 0.02) in all participants. Acute cathodal tDCS over the left vlPFC relative to the left somatosensory cortex reduces reward expectancy-related activity and negative affect post tDCS. Build on these findings, future studies can determine whether chronic cathodal tDCS over the left vlPFC has sustained effects on mood in individuals with Bipolar Disorder, to guide new treatment developments for the disorder.