TASK-BASED ONGOING THETA-GAMMA COUPLING TRACKS PROCESSING SPEED GAINS FOLLOWING SIX-WEEK PREFRONTAL TRANSCRANIAL DIRECT CURRENT STIMULATION IN MAJOR DEPRESSIVE DISORDER

Processing-speed deficits are a core cognitive feature of major depressive disorder (MDD) that often persist despite mood improvement. Although prefrontal transcranial direct current stimulation (tDCS) shows promise for cognitive remediation, the neural dynamics underlying such gains remain unclear. This study examined whether task-based ongoing theta–gamma coupling (TGC) reflects within-person improvements in processing speed following neuromodulation.
Forty-eight outpatients with MDD underwent six weeks of prefrontal tDCS. High-density electroencephalography was recorded during a cognitive task, and processing speed was assessed using the Digit Symbol Substitution Test (DSST) at baseline and post-treatment. Task-based ongoing TGC was quantified across nine fronto–temporo–parietal regions of interest.
After treatment, DSST scores significantly improved (p<0.001), alongside reductions in depressive symptoms. While group-level TGC changes were not uniform, longitudinal analyses revealed that individual increases in task-based ongoing TGC significantly covaried with greater DSST gains across all regions (r=0.34–0.45, q<0.02). These associations remained robust after controlling for baseline performance, demographic factors, and influential observations. Importantly, TGC changes were linked specifically to cognitive improvement rather than mood change.
These findings identify task-based ongoing TGC as a sensitive neurophysiological marker of cognitive recovery in MDD. We propose that strengthening continuous cross-frequency coordination is a key mechanism through which prefrontal tDCS facilitates processing-speed enhancement, supporting biomarker-informed neuromodulation strategies.
This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: RS-2024-00439193).