Modulation of Nigrofugal and Pallidofugal Pathways in Deep Brain Stimulation for Parkinson Disease

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established surgical therapy for patients with Parkinson disease (PD).

To define the role of adjacent white matter stimulation in the effectiveness of STN-DBS.

We retrospectively evaluated 43 patients with PD who received bilateral STN-DBS. The volumes of activated tissue were analyzed to obtain significant stimulation clusters predictive of 4 clinical outcomes: improvements in bradykinesia, rigidity, tremor, and reduction of dopaminergic medication. Tractography of the nigrofugal and pallidofugal pathways was performed. The significant clusters were used to calculate the involvement of the nigrofugal and pallidofugal pathways and the STN.

The clusters predictive of rigidity and tremor improvement were dorsal to the STN with most of the clusters outside of the STN. These clusters preferentially involved the pallidofugal pathways. The cluster predictive of bradykinesia improvement was located in the central part of the STN with an extension outside of the STN. The cluster predictive of dopaminergic medication reduction was located ventrolateral and caudal to the STN. These clusters preferentially involved the nigrofugal pathways.

Improvements in rigidity and tremor mainly involved the pallidofugal pathways dorsal to the STN. Improvement in bradykinesia mainly involved the central part of the STN and the nigrofugal pathways ventrolateral to the STN. Maximal reduction in dopaminergic medication following STN-DBS was associated with an exclusive involvement of the nigrofugal pathways.