Frequency-resolved connectome alterations in major depressive disorder: A multisite resting fMRI study

Background: Functional connectome studies have revealed widespread connectivity alterations in major depressive disorder (MDD). However, the low frequency bandpass filtering (0.01–0.08 Hz or 0.01–0.1 Hz) in most studies have impeded our understanding on whether and how these alterations are affected by frequency of interest. Methods: Here, we performed frequency-resolved (0.01–0.06 Hz, 0.06–0.16 Hz and 0.16–0.24 Hz) connectome analyses using a large-sample resting-state functional MRI dataset of 1002 MDD patients and 924 healthy controls from seven independent centers. Results: We reported significant frequency-dependent connectome alterations in MDD in left inferior parietal, inferior temporal, precentral, and fusiform cortices and bilateral precuneus. These frequency-dependent connectome alterations are mainly derived by abnormalities of medium- and long-distance connections and are brain network-dependent. Moreover, the connectome alteration of left precuneus in high frequency band (0.16–0.24 Hz) is significantly associated with illness duration. Limitations: Multisite harmonization model only removed linear site effects. Neurobiological underpinning of alterations in higher frequency (0.16–0.24 Hz) should be further examined by combining fMRI data with respiration, heartbeat and blood flow recordings in future studies. Conclusions: These results highlight the frequency-dependency of connectome alterations in MDD and the benefit of examining connectome alteration in MDD under a wider frequency band.