Distinct roles of the human cuneiform and pedunculopontine nuclei in gait initiation and freezing of gait

Distinct roles of the human cuneiform and pedunculopontine nuclei in gait initiation and freezing of gait | bioRxiv Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search New Results Distinct roles of the human cuneiform and pedunculopontine nuclei in gait initiation and freezing of gait Mathieu Yeche , Antoine Collomb-Clerc , Katia Lehongre , Julie Bourilhon , Yannick Mullié , Nathalie George , David Grabli , Huiling Tan , Marco Romanato , Claire Olivier , Hayat Belaid , Brian Lau , Carine Karachi , View ORCID Profile Marie-Laure Welter doi: https://doi.org/10.64898/2026.01.13.699281 Mathieu Yeche 1 Sorbonne Université, Institut du Cerveau - Paris Brain Institute, Inserm, CNRS, AP-HP, Hôpital de la Pitié-Salpetrière , 47 Boulevard de l’Hôpital, 75013 Paris, France PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Antoine Collomb-Clerc 1 Sorbonne Université, Institut du Cerveau - Paris Brain Institute, Inserm, CNRS, AP-HP, Hôpital de la Pitié-Salpetrière , 47 Boulevard de l’Hôpital, 75013 Paris, France 2 NeuroX Institute and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL) , Lausanne, Switzerland PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Katia Lehongre 1 Sorbonne Université, Institut du Cerveau - Paris Brain Institute, Inserm, CNRS, AP-HP, Hôpital de la Pitié-Salpetrière , 47 Boulevard de l’Hôpital, 75013 Paris, France PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Julie Bourilhon 1 Sorbonne Université, Institut du Cerveau - Paris Brain Institute, Inserm, CNRS, AP-HP, Hôpital de la Pitié-Salpetrière , 47 Boulevard de l’Hôpital, 75013 Paris, France 3 Department of Neurophysiology, Rouen University Hospital , France MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Yannick Mullié 1 Sorbonne Université, Institut du Cerveau - Paris Brain Institute, Inserm, CNRS, AP-HP, Hôpital de la Pitié-Salpetrière , 47 Boulevard de l’Hôpital, 75013 Paris, France PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Nathalie George 1 Sorbonne Université, Institut du Cerveau - Paris Brain Institute, Inserm, CNRS, AP-HP, Hôpital de la Pitié-Salpetrière , 47 Boulevard de l’Hôpital, 75013 Paris, France PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site David Grabli 1 Sorbonne Université, Institut du Cerveau - Paris Brain Institute, Inserm, CNRS, AP-HP, Hôpital de la Pitié-Salpetrière , 47 Boulevard de l’Hôpital, 75013 Paris, France 4 D epartment of Neurology, Hôpital de la Pitié-Salpetrière, AP-HP , Paris, France MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Huiling Tan 5 MRC Brain Network Dynamics Unit at the University of Oxford , Oxford, United Kingdom PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Marco Romanato 1 Sorbonne Université, Institut du Cerveau - Paris Brain Institute, Inserm, CNRS, AP-HP, Hôpital de la Pitié-Salpetrière , 47 Boulevard de l’Hôpital, 75013 Paris, France PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Claire Olivier 1 Sorbonne Université, Institut du Cerveau - Paris Brain Institute, Inserm, CNRS, AP-HP, Hôpital de la Pitié-Salpetrière , 47 Boulevard de l’Hôpital, 75013 Paris, France Find this author on Google Scholar Find this author on PubMed Search for this author on this site Hayat Belaid 1 Sorbonne Université, Institut du Cerveau - Paris Brain Institute, Inserm, CNRS, AP-HP, Hôpital de la Pitié-Salpetrière , 47 Boulevard de l’Hôpital, 75013 Paris, France 6 Department of Neurosurgery, Hôpital de la Pitié-Salpetrière, AP-HP , Paris, France MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Brian Lau 1 Sorbonne Université, Institut du Cerveau - Paris Brain Institute, Inserm, CNRS, AP-HP, Hôpital de la Pitié-Salpetrière , 47 Boulevard de l’Hôpital, 75013 Paris, France PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Carine Karachi 1 Sorbonne Université, Institut du Cerveau - Paris Brain Institute, Inserm, CNRS, AP-HP, Hôpital de la Pitié-Salpetrière , 47 Boulevard de l’Hôpital, 75013 Paris, France 6 Department of Neurosurgery, Hôpital de la Pitié-Salpetrière, AP-HP , Paris, France MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Marie-Laure Welter 1 Sorbonne Université, Institut du Cerveau - Paris Brain Institute, Inserm, CNRS, AP-HP, Hôpital de la Pitié-Salpetrière , 47 Boulevard de l’Hôpital, 75013 Paris, France 3 Department of Neurophysiology, Rouen University Hospital , France MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Marie-Laure Welter For correspondence: marielaure.welter{at}icm-institute.org Abstract Full Text Info/History Metrics Supplementary material Preview PDF Abstract Freezing of gait in Parkinson’s disease (PD) is a major cause of disability, often resistant to dopaminergic therapy and deep brain stimulation (DBS). Its underlying mechanisms remain unclear, mainly because the roles of the human mesencephalic locomotor region (MLR) nuclei are not well understood. Here, we combined rare local field potentials (LFP) recordings from the cuneiform (CuN) and pedunculopontine nuclei (PPN) with biomechanical markers of gait initiation (GI) in four PD patients. We identified functional differences: increases in CuN alpha-band activity precede anticipatory postural adjustments (APA) and correlate with the rhythm of upcoming steps, whereas decreases in PPN beta-band activity occur during APA just before the lead foot lifts off. Imminent freezing is characterized by a breakdown of this organization, marked by mistimed alpha-band surges across the MLR and abnormal PPN beta-band modulation. CuN stimulation selectively improved the stepping rhythm, while PPN stimulation worsened pace or forward vigor. Furthermore, exaggerated mesencephalic alpha-band power was associated with poor clinical responses. These results clarify the individual roles of MLR nuclei in human locomotion and identify pathological alpha dynamics as a biomarker for advancing adaptive neurostimulation. Competing Interest Statement The authors have declared no competing interest. Funder Information Declared Michael J. Fox Foundation, https://ror.org/03arq3225 Agence Nationale de la Recherche, https://ror.org/00rbzpz17 European Regions Research and Innovation Network, https://ror.org/02wbb9367 Swiss National Science Foundation Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . Back to top Previous Next Posted January 14, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. 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