Neural pathways associated with reduced rigidity during pallidal deep brain stimulation for Parkinson's disease

Area of Science:

• Neuroscience
• Biophysics
• Computational Biology

Background:

• Parkinson's disease (PD) is characterized by motor symptoms like muscle rigidity.
• Deep brain stimulation (DBS) of the globus pallidus internus (GPi) effectively reduces rigidity in PD.
• The precise neural mechanisms underlying GPi DBS-induced rigidity reduction remain unclear.

Purpose of the Study:

• To investigate the neural pathways responsible for rigidity reduction via GPi DBS in Parkinson's disease.
• To utilize subject-specific biophysical models to analyze the contribution of different neural pathways to GPi DBS effects.
• To determine if the location of GPi stimulation influences the activation of specific pathways and subsequent rigidity changes.

Main Methods:

• Generated subject-specific biophysical models of GPi DBS using 7-T MRI data.
• Included pallidal efferent, putamenal efferent, and internal capsule pathways in the models.
• Measured forearm rigidity in 10 individuals (17 arms) with PD off medication under varying DBS conditions (optimized, dorsal GPi, ventral GPi) using a robotic manipulandum.

Main Results:

• Clinically optimized GPi DBS significantly reduced forearm rigidity (P < 0.001).
• Model simulations showed GPi efferent fiber activation correlated with rigidity reduction.
• The model indicated GPi efferent axons can be activated along the entire dorsal-ventral axis of the GPi.

Conclusions:

• Rigidity reduction in PD patients treated with GPi DBS is primarily mediated by the activation of GPi efferent pathways to the thalamus.
• This activation likely reduces muscle stretch reflex excitability through overdriving pallidofugal output.
• Subject-specific computational modeling is a valuable tool for understanding the mechanisms of neuromodulation in PD.