Dorsal Column Spinal Cord Stimulation Attenuates Brain-Spine Connectivity through Locomotion and Visuospatial-Specific Area Activation in Progressive Freezing of Gait

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 freezing of gait (PPGF), 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, are 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. DBS and SCS have been tested as therapeutic neuromodulation avenues for FOG with mixed outcomes. Methods: We analyzed gait and balance in three patients with PSP-PGF who received percutaneous thoracic spinal cord stimulation (SCS) and utilized magnetoencephalography (MEG), electroencephalography (EEG), and electromyography (EMG) 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.