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The pathophysiology underlying Parkinson's disease (PD) speech impairments and its potential sex differences remain unclear. We investigated sex-specific alterations in speech and striato-cortical networks in 104 patients with early PD (68M/36F), and 44 healthy controls (23M/21F), using quantitative speech markers and multimodal neuroimaging. Speech features related to prosody, phonation, articulation, fluency, and rhythm, were extracted from voice recordings; striatal dopaminergic loss was quantified using DaT-SPECT, and functional connectivity between striatal and cortical language networks was analyzed with resting-state fMRI. Results showed that PD-related speech impairments were more pronounced in males. Functional connectivity was globally reduced in PD, but female patients exhibited higher caudate-cortical connectivity. In males, speech deficits were associated with both dopaminergic loss and connectivity disruption, whereas in females, only connectivity changes were involved. These findings revealed sex-specific pathophysiological mechanisms in early PD speech disorders, emphasizing the need for sex-stratified approaches in research and clinical practice.
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