Altered intrinsic brain activity and cognitive impairment in euthymic, unmedicated individuals with bipolar disorder

Cognitive impairment in euthymic bipolar disorder (BD) contributes to poor functional outcomes. Resting-state magnetic resonance imaging (MRI)may help us understand the neurobiology of cognitive impairment in BD. Here, forty unmedicated euthymic BD patients and thirty-nine healthy controls were recruited, undergoing MRI scans and neuropsychological measures. The amplitude of low-frequency fluctuation (ALFF) and ALFF-based functional connectivity (FC) analysis was employed to explore the potential alterations of neural activity. Voxel-wised correlation was calculated between clinical and cognitive variables and abnormal brain activity. Compared with healthy controls, euthymic BD patients showed worse cognitive performance in Trail Making Test, Digit Span Test, and Stroop Color-Word Test (SCWT). The euthymic BD group had significantly lower ALFF in the left medial frontal gyrus, right middle frontal gyrus, right postcentral gyrus, and left superior frontal gyrus. Furthermore, we found decreased ALFF values in the right middle frontal gyrus that was negatively correlated with cognitive inhibition, (r = -0.43, P = 0.015). ALFF-based FC analysis showed that BD group showed significantly decreased FC between the right middle frontal gyrus (seed) and left middle temporal gyrus and left medial frontal gyrus, (Two-tailed, P_FWE < 0.05, TFCE corrected). The findings demonstrated that individuals with BD during the euthymic phase exhibited decreased ALFF and hypoconnectivity of key brain areas within the frontoparietal network. These altered spontaneous brain activity in euthymic BD patients may be involved in the pathophysiology mechanism of cognitive deficits.