Neural correlates of cognitive improvement over time in patients newly diagnosed with bipolar disorder

There is currently no known effective long-term treatment for cognitive impairments in bipolar disorder (BD) and understanding of the neurobiological mechanisms underlying cognitive impairments in BD is lacking. Identifying potential biomarkers for cognitive improvement is essential to aid targeted interventions. This study investigates the neural correlates of cognitive improvement versus lack of improvement over time in BD. Forty-six patients newly diagnosed with BD who recently began treatment in a specialized outpatient clinic and 38 healthy control individuals (HC) were assessed with a battery of neuropsychological tests and a verbal n-back working memory test during functional magnetic resonance imaging (fMRI) at baseline and follow-up (mean: 15 months). Patients were divided into two groups: those who improved cognitively over time, defined as global cognition change $\ge$ .2 SD, (BD+: n = 27) and those who showed a lack of normative improvement (BD-: n = 19). BD + showed hypoactivity in dorsolateral prefrontal cortex (dlPFC) and dorsomedial prefrontal cortex (dmPFC) compared to HC, both at baseline and follow-up. Hypoactivity in these prefrontal regions correlated with poorer out-of-scanner working memory and executive function for BD- and HC, but not for the BD + group. While hypoactivity did not predict change in cognition for BD+, it did predict improvement in functioning for both patient subgroups. The findings from this exploratory study suggest that dlPFC hypoactivity may identify those who are likely to respond well to treatment and show an improvement in functioning over time.