State-Dependent Modulation of a Theta-Responsive Subnetwork by High-Frequency Stimulation of the Ventral Striatum

The ventral striatum (VS) is a promising target for deep brain stimulation (DBS) for the treatment of refractory psychiatric disorders. The therapeutic effects of DBS rely on altering neural activity within specific networks; however, the network-level oscillatory mechanisms underlying VS-DBS remain unclear. Here, in human subjects with DBS electrodes implanted in the VS and anterior limb of the internal capsule, electroencephalography recordings obtained during DBS ON and OFF conditions revealed a global suppression of theta activity. To isolate these effects specific to VS stimulation, we applied direct electrical stimulation to the VS in two rhesus monkeys while simultaneously recording intracranial local field potentials from the reward-network regions. High-frequency stimulation (HFS) of the VS elicited target-specific, current-dependent, state-dependent, and distributed modulation of theta activity, whose magnitude was related to effective connectivity. Overall, VS-HFS exerted state-dependent modulation of a theta-responsive subnetwork. These findings may help to elucidate the therapeutic mechanisms of VS-DBS.