Background: Walking becomes more and more degraded as Parkinson's Disease (PD) progresses. Previous research examined factors contributing to this deterioration. Among them, changes in brain cortical activity during walking have been less studied in this clinical population.Objectives: This study aimed to: (1) investigate changes in dorsolateral prefrontal cortex (DLPFC) activation during usual walking and dual-task walking conditions in patients with PD; (2) examine the association between cortical activity and behavioral/cognitive outcomes; and (3) explore which factors best predict increased activation of the DLPFC during usual walking.Methods: Eighteen patients with early stage PD and 18 controls performed 4 conditions: (1) standing while subtracting, (2) usual walking, (3) walking while counting forward, and (4) walking while subtracting. Cortical activity in DLPFC, assessed by changes in oxy-hemoglobin (ΔHbO2) and deoxy-hemoglobin (ΔHbR), was measured using functional near infrared spectroscopy (fNIRS). Gait performance was recorded using wearables sensors. Cognition was also assessed using neuropsychological tests, including the Trail Making Test (TMT).Results: DLPFC activity was higher in patients compared to controls during both usual walking and walking while subtracting conditions. Patients had impaired walking performance compared to controls only during walking while subtracting task. Moderate-to-strong correlations between ΔHbO2 and coefficients of variation of all gait parameters were found for usual walking and during walking while counting forward conditions. Part-B of TMT predicted 21% of the variance of ΔHbO2 during usual walking after adjustment for group status.Conclusions: The increased DLPFC activity in patients during usual walking suggests a potential compensation for executive deficits. Understanding changes in DLPFC activity during walking may have implications for rehabilitation of gait in patients with PD.

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Highlights Patients with Parkinson’s disease have increased prefrontal activity during usual walking. After SIROCCO training, prefrontal activity decreased and gait performance improved in patients. An intensive exercise-based training program increased automaticity of gait in patients with PD. Findings highlight the potential of neuroplasticity in PD after exercise.