Deep Brain Stimulation Modulates Gamma Oscillations and Theta-Gamma Coupling in Treatment Resistant Depression

- Major depression patients with implanted DBS in the subcallosal cingulate gyrus were recruited.
- Patients performed N-back tasks (0 and 3 back) during EEG recordings with DBS ON or OFF.
- DBS ON resulted in significant decrease of frontal beta and gamma power during the 3-back.
- Decrease in right frontal gamma power associated with a decrease in depressive symptoms.
- Increase in left frontal theta-gamma coupling associated with a decrease in depressive symptoms.

BackgroundDeep brain stimulation (DBS) in the subcallosal cingulate gyrus (SCG) is becoming an effective therapeutic option for treatment resistant depression (TRD).Objective/hypothesisIdentifying the neurophysiological mechanisms altered by DBS may lead to more tailored treatment parameters and enhanced efficacy.MethodsTwenty TRD patients with implanted DBS in the SCG were recruited. Patients participated in three EEG recording sessions, one with DBS ON, one with DBS randomized to ON or OFF, and one with DBS OFF. During each session, subjects performed N-back working memory tasks, namely the 0-back and 3-back. Fourteen subjects with valid EEG were included in the analysis. Changes in frontal gamma oscillations (30-50 Hz) and coupling between theta (4-7 Hz) and gamma oscillations as a result of DBS stimulation were quantified and correlated with depressive symptoms.ResultsDBS stimulation resulted in suppression of frontal oscillations in the ON state relative to the OFF state during the N-back tasks. Greatest suppression was demonstrated in beta and gamma oscillations and most pronounced during the 3-back. Suppression of gamma oscillations in the 3-back correlated with a reduction in depressive symptoms. DBS ON relative to OFF in the 3-back also resulted in an increase in theta-gamma coupling that correlated with a reduction in depressive symptoms.ConclusionSuppression of gamma oscillations and increased theta-gamma coupling through DBS is likely mediated by both SCG activation of inhibitory circuits and an enhancement of plasticity in the frontal cortex. Activation of both pathways may explain the therapeutic properties of DBS in TRD.