Deep Brain Stimulation in Parkinson’s Disease: New and Emerging Targets for Refractory Motor and Nonmotor Symptoms

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative condition characterized by bradykinesia, tremor, rigidity, and postural instability (PI), in addition to numerous nonmotor manifestations. Many pharmacological therapies now exist to successfully treat PD motor symptoms; however, as the disease progresses, it often becomes challenging to treat with medications alone. Deep brain stimulation (DBS) has become a crucial player in PD treatment, particularly for patients who have disabling motor complications from medical treatment. Well-established DBS targets include the subthalamic nucleus (STN), the globus pallidus pars interna (GPi), and to a lesser degree the ventral intermediate nucleus (VIM) of the thalamus. Studies of alternative DBS targets for PD are ongoing, the majority of which have shown some clinical benefit; however, more carefully designed and controlled studies are needed. In the present review, we discuss the role of these new and emerging DBS targets in treating refractory axial motor symptoms and other motor and nonmotor symptoms (NMS).

Methodological Considerations for Neuroimaging in Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson’s Disease Patients

“…Some centers have long preferred the internal segment of the globus pallidus, and more recent research is being conducted on the suitability of alternate areas such as the ventral intermediate nucleus or the pedunculopontine nucleus for DBS targets. For a more in-depth review, please see [ 10 , 239 , 240 ] and the references therein.…”

A diencephalic pathway for movement initiation and rescue of Parkinsonian symptoms

“…Interestingly, Pf-STN terminal excitation was more effective at alleviating akinesia and promoting kinetic behaviors in bilateral-PD mice than Pf-STN cell-body excitation (Figures 3 and 4; Figures S10). Similarly, bilateral CM/Pf-DBS in PD patients has limited therapeutic benefits compared to STN-DBS, suggesting that it cannot control PD motor symptoms adequately [35][36][37] . Given our finding that non-specific optogenetic excitation slows movement ( Figure S3A), it is possible that CM/Pf-DBS in PD patients might recruit conflicting downstream neural circuits that attenuates its therapeutic potential.…”

Proceedings of the Seventh Annual Deep Brain Stimulation Think Tank: Advances in Neurophysiology, Adaptive DBS, Virtual Reality, Neuroethics and Technology

“…Additional small uncontrolled studies are exploring other targets for refractory tremors including the caudal Zona incerta and the centromedian and parafascicular nuclei of the thalamus. Combined PPN and caudal zona incerta stimulation, stimulation of the Centromedian and Parafascicular nuclei of the thalamus, and extradural motor cortex stimulation are other targets currently being investigated for the management of refractory axial symptoms in PD (Anderson et al, 2017). While outcomes are promising, these (and additional) approaches will require further study.…”