Frequency-Dependent Spatial Distribution of Functional Hubs in the Human Brain and Alterations in Major Depressive Disorder

Alterations in large-scale brain intrinsic functional connectivity (FC), i.e., coherence between fluctuations of ongoing activity, have been implicated in major depressive disorder (MDD). Yet, little is known about the frequency-dependent alterations of FC in MDD. We calculated frequency specific degree centrality (DC) - a measure of overall FC of a brain region - within 10 distinct frequency sub-bands accessible from the full range of resting-state fMRI BOLD fluctuations (i.e., 0.01-0.25 Hz) in 24 healthy controls and 24 MDD patients. In healthy controls, results reveal a frequency-specific spatial distribution of highly connected brain regions - i.e., hubs - which play a fundamental role in information integration in the brain. MDD patients exhibited significant deviations from the healthy DC patterns, with decreased overall connectedness of widespread regions, in a frequency-specific manner. Decreased DC in MDD patients was observed predominantly in the occipital cortex at low frequencies (0.01-0.1 Hz), in the middle cingulate cortex, sensorimotor cortex, lateral parietal cortex, and the precuneus at middle frequencies (0.1-0.175 Hz), and in the anterior cingulate cortex at high frequencies (0.175-0.25 Hz). Additionally, decreased DC of distinct parts of the insula was observed across low, middle, and high frequency bands. Frequency-specific alterations in the DC of the temporal, insular, and lateral parietal cortices correlated with symptom severity. Importantly, our results indicate that frequency-resolved analysis within the full range of frequencies accessible from the BOLD signal - also including higher frequencies (> 0.1 Hz) - reveals unique information about brain organization and its changes, which can otherwise be overlooked.