PD patients with pathological fatigue show a selective loss of normal sensory attenuation on a force-matching task, and the degree of attenuation reduction correlates with subjective fatigue but not with motor severity or other nonmotor symptoms.

By linking fatigue to a specific sensorimotor processing deficit this study proposes a measurable biomarker and a mechanistic target (sensory attenuation circuitry) that could guide development of targeted neuromodulation, sensory retraining, or symptom-focused clinical trials for PD fatigue.

Fatigue is a prevalent and disabling nonmotor symptom in Parkinson's disease (PD), yet its underlying mechanisms remain poorly understood. A recent theoretical model proposes that fatigue may arise from impaired sensory attenuation, the normal reduction in perception of self-generated compared with externally generated stimuli. To test this hypothesis, we assessed sensory attenuation in 20 PD patients with fatigue (PDFatigue), 22 without fatigue (PDNoFatigue), and 20 healthy controls (HC) using a force-matching task. Participants reproduced target forces on their left index finger under two conditions: by pressing directly on their own finger (direct condition) or using an external device (indirect condition). HC and PDNo fatigue patients significantly overestimated the required force in the direct compared to the indirect condition, consistent with a normal sensory attenuation. In contrast, PDFatigue patients showed no significant difference between conditions, indicating a selective impairment of sensory attenuation. Within the PDFatigue group, reduced sensory attenuation was strongly associated with greater subjective fatigue and perceived effort, but not with motor symptom severity, disease duration, or other non-motor symptoms commonly co-occurring with fatigue. These findings provide empirical evidence that impaired sensory attenuation may be a fundamental mechanism underlying pathological fatigue in PD. Importantly, this impairment appears unique and specific to fatigue, as it does not correlate with other clinical features of PD or with other nonmotor symptoms. The selective link between sensory attenuation and fatigue offers a promising avenue for the development of targeted interventions and underscores the potential of sensory attenuation as a biomarker of pathological fatigue.