The concurrent disturbance of dynamic functional and structural brain connectome in major depressive disorder: the prefronto-insular pathway

Background Robust evidence has shown that abnormal function networks, particularly the salience network (SN), are observed in depressed patients. Although white matter structural connectivity may predict time-varying functional connectivity, including symptom phenotype, in psychiatric disorders, there is still a gap in elucidating the concurrent dynamic functional and structural connectivity profiles of the SN in depressed patients. Methods We measured static and dynamic functional connectivity (FC) of the SN using resting-state fMRI BOLD time series in 76 subjects (21 with major depressive disorder (MDD), 27 with bipolar depression (BD), and 28 healthy controls (HC)). Hamilton Depression Scale total score was used to measure depression severity. Furthermore, we investigated the concurrent structural connectivity using diffusion kurtosis imaging (DKI)-based tractography. Results Our findings suggested that in the presence of MDD, both structural and dynamic (but not static) FC were reduced in the SN, particularly affecting the left prefronto-insular pathways (L.aPFC-L.insula). MDD patients showed decreased connectivity variability within the SN compared with HC. The aberrant dynamic FC in the prefronto-insular pathways of the SN related to severity of depressive symptoms in MDD. Furthermore, compared with BD patients, those with MDD showed significantly decreased dynamic FC in the left prefronto-parietal system (L.aPFC-lateral parietal cortex). Limitations The generalizability of our findings is, to some extent, constrained by the small sample size. Conclusions The integrity of SN connectivity, particularly the prefronto-insular pathway, appears to be a crucial signature of MDD. The perturbed dynamic interaction of SN with prefrontal regions may underlie the clinical severity in depressed patients.