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BACKGROUND: Freezing of gait (FOG) in Parkinson's disease (PD) is a disabling motor symptom with unclear pathophysiology. Beyond known basal ganglia dysfunction and cognitive impairment, sensory integration deficits are increasingly key, though their cortical network mechanisms during walking remain poorly understood. OBJECTIVE: This study used functional near-infrared spectroscopy (fNIRS) during sensory-contextual walking to clarify FOG-related cortical network dynamics, aiming to: (1) Characterize FOG-specific cortical responses to sensory challenges; (2) Distinguish PD-specific versus FOG-associated cortical network dysfunction; (3) Explore dopaminergic modulation of these mechanisms. METHODS: 40 PD patients 20 with FOG (PD-FOG), 20 without FOG (PD-nFOG) and 23 healthy-controls (HC) completed four walking tasks routine Walking-on-Ground (WG), Walking-on-Foam with proprioceptive challenge (WF), Walking-through-Narrow-gate with visuospatial challenge (WN), and Walking-through-Slope with combined proprioceptive/visuospatial challenges (WS) under OFF and ON dopaminergic medications. Cortical hemodynamics in the Supplementary Motor Area (SMA), Primary Motor Cortex (M1), Primary Somatosensory Cortex (S1), Somatosensory Association Cortex (SAC), Prefrontal Cortex (PFC), and Frontal Eye Field (FEF), as well as walking performance were recorded. Group and medication-state differences were analyzed using ANOVA models. RESULTS: (1) PD-FOG lacked adaptive cortical plasticity (activation/connectivity response) to increasing sensory demands compared to PD-nFOG/HC; (2) PD-FOG exhibited cognitive-sensory/motor hyperconnectivity versus PD-nFOG during WF. PD patients showed widespread sensory-mediated hyperconnectivity and focal sensorimotor hyperactivation during WG/WN versus HC, but FEF hypoactivation during WS; (3) Medication improved gait but suppressed sensorimotor activation and reduced frontoparietal connectivity in PD-FOG; (4) Elevated M1-SMA connectivity predicted OFF-medication FOG, while elevated S1-FEF connectivity predicted ON-medication FOG. Daily FOG severity correlated with distinct OFF-/ON-medication connectivity patterns. CONCLUSION: This study reveals a medication-dependent, biphasic cortical dysfunction in PD-FOG. The OFF-medication state shows compensatory hyperconnectivity that fails under sensory challenges, indicating deficient plasticity, whereas the ON-medication state exhibits a paradoxical suppression of sensorimotor and integrative networks despite gait improvement. This reconceptualizes FOG as a dynamic network adaptation failure and points to state-specific therapeutic strategies. Registration number ChiCTR2300072744.
Chen et al. (Fri,) studied this question.