Treatment Resistance in Bipolar Disorder is Associated with Intrinsic Network Power

Background Treatment for bipolar disorder (BD) is often suboptimal, with over 50% of patients becoming treatment refractory. To better understand the neural mechanisms underlying treatment response, we investigated the functional magnetic resonance imaging (fMRI) signal of resting-state networks (RSNs) and compared network connectivity and spectral power across treatment-refractory BD, remitted BD, and psychiatrically healthy control groups. Methods Resting-state fMRI time series underwent group independent component analysis. Signal components were anatomically assigned to intrinsic RSNs. Time-course spectral power and spatial map intensity were compared across groups, adjusting for age, sex, and mood state. Results Group differences in power spectra were found across several RSNs. The central executive network (CEN) differed across all groups in the superior parietal lobule and left middle frontal gyrus, and between both BD groups and the control group (n=13) in the frontal pole and supramarginal gyrus. The default mode network (DMN) differed between refractory (n=12) and remitted (n=13) groups in the frontal cortex. The salience network (SN) showed differences between the refractory and control groups in the cingulate, insular, frontal operculum, and middle frontal gyrus. Lastly, the lateral visual network differed between the remitters and control groups. Conclusion Resting state oscillations in the CEN, DMN, and SN, networks previously implicated in BD and treatment-resistant major depressive disorder, may be a signature of treatment response in BD. Frequency-specific alterations, particularly in frontal and cingulate regions, align with prior structural findings, suggesting entrenched neural disruptions and possible functional reorganization in treatment-refractory BD, highlighting potential targets for future interventions.