Subthalamic deep brain stimulation restores automatic response activation and increases susceptibility to impulsive behavior in patients with Parkinson’s disease

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Abstract

Repeatedly reported deficits of patients with Parkinson’s disease (PD) in selecting an appropriate action in the face of competing response alternatives has led to the conclusion of a basal ganglia (BG) involvement in response selection and impulse control. Despite capacious research, it remains elusive how BG dysfunction affects processes subserving goal-directed behavior. Even more problematically, since PD pathology transcends a BG dysfunction due to dopamine depletion in the nigrostriatal DA system (by also comprising alterations in extrastriatal dopamine availability and other neurotransmitter systems), it is not yet clear which aspects of these deficits are actually caused by BG dysfunction. To address this question, the present study investigated 13 off-medication PD patients with bilateral therapeutic subthalamic deep brain stimulation (DBS) both with and without stimulation (DBSON and DBSOFF, respectively) and 26 healthy controls. All participants performed a task that tests the relation between automatic response impulses and goal-directed action selection. Results show an improvement of automatic response activation under DBSON, increasing the susceptibility to impulsive responses, and a reduced impact of automatic response activation under DBSOFF. We argue that the BG determine the efficiency of the regulation and transmission of stimulus-driven bottom-up response activation required for efficient response selection.

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