Cortical network mechanisms in subcallosal cingulate deep brain stimulation for depression

Identifying functional biomarkers of clinical success can contribute to therapy optimization, and provide insights into the pathophysiology of treatment-resistant depression and mechanisms underlying the potential restorative effects of subcallosal cingulate deep brain stimulation. Magnetoencephalography data were obtained from 15 individuals who underwent subcallosal cingulate deep brain stimulation for treatment-resistant depression and 25 healthy subjects. The first objective herein was to identify region-specific oscillatory modulations for the identification of discriminative network nodes expressing (i) pathological differences in TRD (responders and non-responders, stimulation-OFF) compared to healthy subjects, which (ii) were counteracted by stimulation in a responder-specific manner. The second objective of this work was to further explore the mechanistic effects of stimulation intensity and frequency. Oscillatory power analyses led to the identification of discriminative regions that differentiated responders from non-responders based on modulations of increased alpha (8-12 Hz) and decreased gamma (32-116 Hz) power within nodes of the default mode, central executive, and somatomotor networks, Brocas area, and lingual gyrus. Within these nodes, it was also found that low stimulation frequency had stronger effects on oscillatory modulation than increased stimulation intensity. The identified discriminative network profile implies modulation of pathological activities in brain regions involved in emotional control/processing, motor control, and the interaction between speech, vision, and memory, which have all been implicated in depression. This modulated network profile may represent a functional substrate for therapy optimization. Stimulation parameter analyses revealed that oscillatory modulations can be strengthened by increasing stimulation intensity or, to an even greater extent, by reducing frequency.