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.