Single-Trajectory Multiple-Target Deep Brain Stimulation for Parkinsonian Mobility and Cognition

Area of Science:

• Neurology
• Neurosurgery
• Neuroscience

Background:

• Deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) is being explored for cognitive dysfunction.
• Advanced Parkinson's disease (PD) often involves cognitive impairment.

Purpose of the Study:

• To assess the feasibility and safety of globus pallidus pars interna (GPi) and NBM DBS in advanced PD patients with cognitive impairment.
• To evaluate the acute effects of NBM stimulation on attention and cognitive measures.
• To investigate neuroimaging biomarkers associated with NBM stimulation.

Main Methods:

• A phase-II, double-blind, crossover pilot trial involving six participants.
• Assessment of safety, cognitive measures, and motor data at one year.
• Neuroimaging analysis to identify biomarkers.

Main Results:

• NBM DBS was well-tolerated but did not yield significant cognitive improvements.
• GPi DBS demonstrated significant improvement in dyskinesia and motor fluctuations (P=0.04) at one year.
• NBM stimulation altered neuroimaging biomarkers, including reduced frontal and parietal glucose metabolism and increased power and connectivity, with left NBM VTA linked to stable cognition.

Conclusions:

• Simultaneous GPi and NBM stimulation is safe and effective for improving motor complications in advanced PD.
• While NBM stimulation impacts neuroimaging biomarkers, it did not result in sustained cognitive benefits in this cohort.