Background: Major depressive disorder is a debilitating psychiatric condition with high rates of treatment resistance that may be associated with working memory (WM) deficits. For treatment resistant depression (TRD) patients, deep brain stimulation (DBS) is emerging as an effective therapeutic option. Objective: To determine if electroencephalography signals recorded during DBS ON and OFF states while performing WM tasks can serve as biomarkers of therapeutic efficacy for DBS in TRD patients. Results: DBS stimulation suppressed frontal gamma oscillations (30–50Hz) during the ON state relative to the OFF state, an effect that was more pronounced with higher WM load. This suppression strongly correlated with depressive symptoms reduction. Conclusion: Suppression of gamma oscillations by DBS is likely mediated by indirect activation of inhibitory circuits in the frontal cortex. It represents a potential treatment biomarker for DBS in TRD and may lead to more tailored treatment parameters that can result in enhanced efficacy.

Background: Major depressive disorder is a debilitating psychiatric condition with high rates of treatment resistance that may be associated with working memory (WM) deficits. For treatment resistant depression (TRD) patients, deep brain stimulation (DBS) is emerging as an effective therapeutic option. Objective: To determine if electroencephalography signals recorded during DBS ON and OFF states while performing WM tasks can serve as biomarkers of therapeutic efficacy for DBS in TRD patients. Results: DBS stimulation suppressed frontal gamma oscillations (30–50Hz) during the ON state relative to the OFF state, an effect that was more pronounced with higher WM load. This suppression strongly correlated with depressive symptoms reduction. Conclusion: Suppression of gamma oscillations by DBS is likely mediated by indirect activation of inhibitory circuits in the frontal cortex. It represents a potential treatment biomarker for DBS in TRD and may lead to more tailored treatment parameters that can result in enhanced efficacy.