Abstract
Introduction: Freezing of gait (FOG) is a clinical phenomenon with major life impairments and significant reduction in quality of life for affected patients. FOG is a feature of Parkinson’s disease and a hallmark of primary progressive FOG, currently reclassified as Progressive Supranuclear Palsy-progressive gait freezing (PSP-PGF). The pathophysiology of FOG and particularly PGF, which is a rare degenerative disorder with a progressive natural history of gait decline, is poorly understood. Mechanistically, changes in oscillatory activity and synchronization in frontal cortical regions, the basal ganglia, and the midbrain locomotor region have been reported, indicating that dysrhythmic oscillations and coherence could play a causal role in the pathophysiology of FOG. Deep brain stimulation and spinal cord stimulation (SCS) have been tested as therapeutic neuromodulation avenues for FOG with mixed outcomes. Methods: We analyzed gait and balance in 3 patients with PSP-PGF who received percutaneous thoracic SCS and utilized magnetoencephalography (MEG), electroencephalography, and electromyography to evaluate functional connectivity between the brain and spine. Results: Gait and balance did not worsen over a 13-month period. This observation was accompanied by decreased beta-band spectral power in the whole brain and particularly in the basal ganglia. This was accompanied by increased functional connectivity in and between the sensorimotor cortices, basal ganglia, temporal cortex, and cerebellum, and a surge in corticomuscular coherence when SCS was paired with visual cues. Conclusion: Our results suggest synergistic activity between brain and spinal circuits upon SCS for FOG in PGF, which may have implications for future brain-spine interfaces and closed-loop neuromodulation for patients with FOG.
Published Version
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