Striatal network dysfunction underlying speech impairment in early Parkinson’s disease

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. The authors would like to thank Alizé Chalençon, Manon Gomes, Valentine Mahéo, Christelle Laganot, and Sandrine Bataille for their contributions to the audio acquisitions, Mélanie Didier, Stéphanie Anastacio, Céline Homo, Christine Soeung, Margaux Couppey, Ayoub Ouachani, and Frédéric Humbert for their contributions to the MRI acquisitions. The authors express their sincere appreciation to the subjects and their families for their participation in this research.

This work was funded by grants from ANR Nucleipark, DHOS-Inserm, France Parkinson, Ecole des NeuroSciences de Paris (ENP), Fondation pour la Recherche Médicale (FRM), Investissements d'Avenir program (ANR-10-IAIHU-06 and ANR-11-INBS-0006), ERA PerMed EU-wide project DIGIPD, Fondation d’Entreprise EDF, BIOGEN Inc., Fondation Thérèse and René Planiol, Energipole (M. Mallart), and Société Française de Médecine Esthétique (M. These authors contributed equally: Caitlin Paige Rogers, Sandy Mournet.

Institut du Cerveau – ICM, Inserm, CNRS, Sorbonne University, Paris, France Caitlin Paige Rogers, Sandy Mournet, Cécile Gallea, Graziella Mangone, Sara Sambin, Lydia Chougar, Rahul Gaurav, Isabelle Arnulf, Jean-Christophe Corvol, Marie Vidailhet, Stéphane Lehéricy & Laetitia Jeancolas Biological Sciences Department, Columbia University, New York, NY, USA Department of Neurosciences, Imaging, and Clinical Sciences, Institute for Advanced Biomedical Technologies, ‘G. D’Annunzio’ University of Chieti-Pescara, Chieti, Italy AP-HP, Department of Neurology, Pitié-Salpêtrière Hospital, Paris, France Graziella Mangone, Sara Sambin, Nicolas Villain, Jean-Christophe Corvol & Marie Vidailhet AP-HP, Department of Neuroradiology, Pitié-Salpêtrière Hospital, Paris, France AP-HP, Sleep disorders unit, Pitié-Salpêtrière Hospital, Paris, France AP-HP, Department of Nuclear Medicine, Pitié-Salpêtrière Hospital, Paris, France CNRS, INSERM, Laboratoire d’Imagerie Biomédicale, LIB, Sorbonne University, Paris, France Laboratoire SAMOVAR, Télécom SudParis, Institut Polytechnique de Paris, Palaiseau, France Electrical & Computer Engineering Department, PERFORM Centre, Concordia University, Montreal, QC, Canada The authors declare no competing interests. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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