Cross-frequency coupling between low frequency and gamma oscillations altered in cognitive biotype of depression

The cognitive biotype of depression has been conceptualized as a distinct subtype characterized by unique distinct neural correlates and specific clinical features. Abnormal neural oscillations related to cognitive dysfunction have been extensively studied, with particular attention given to gamma oscillations due to their crucial role in neurocircuit operations, emotional processing, and cognitive functions. Nevertheless, cross-frequency coupling between low frequency and gamma oscillations in the cognitive biotype of depression have yet to be fully elucidated.

The study identified the cognitive biotype in depression by MATRICS Consensus Cognitive Battery (MCCB). We enrolled 141 depressed patients in remission, including 56 identified as cognitive biotype and 85 as the non-cognitive impairment subgroup. Cross-frequency coupling between low frequency and gamma oscillations were analyzed using specific computational methods based on the data collected by Electroencephalogram (EEG). Furthermore, we did correlation analysis to explore the relationship between cross-frequency coupling of neural oscillations with cognitive function in depression.

We found that phase-amplitude coupling (PAC) values decreased in cognitive biotype. Specifically, cross-frequency coupling between theta (Pz: t =-3.512, FDR-corrected p = 0.011), alpha (P3: t =-3.377, FDR-corrected p = 0.009; Pz: t =-3.451, FDR-corrected p = 0.009), beta (P3: t =-3.129, FDR-corrected p = 0.020; Pz: t =-3.333, FDR-corrected p = 0.020) with low gamma decreased at eyes-closed state in cognitive biotype. However, cross-frequency coupling between delta with gamma increased in cognitive biotype (P4: t = 3.314, FDR-corrected p = 0.022) While cross-frequency coupling exhibited no significant differences at eyes-opened state in two subgroups (FDR-corrected p > 0.05). Furthermore, significant correlations between cognitive function and cross-frequency coupling at eyes-closed state were observed.

These results indicated that the cross-frequency coupling between low frequency and gamma occurred in the parietal lobe in cognitive biotype of depression. These results advance the understanding of neurophysiological mechanisms underlying cognitive deficits and highlight potential biomarkers for precision depression.