Subthalamic deep brain stimulation alleviates motor symptoms without restoring deficits in corticospinal suppression during movement preparation in Parkinson’s disease

Background Parkinson’s disease (PD) patients exhibit alterations in neurophysiological mechanisms underlying movement preparation, especially the suppression of corticospinal excitability – called “preparatory suppression” – considered to propel movement execution by increasing motor neural gain in healthy individuals. Objective Deep brain stimulation (DBS) of the subthalamic nucleus (STN) being an attractive treatment for advanced PD, we aimed to investigate the potential contribution of this nucleus to PD-related changes in such corticospinal dynamics. Methods On two consecutive days, we applied single-pulse transcranial magnetic stimulation over both primary motor cortices in 20 PD patients treated with bilateral STN-DBS (ON vs. OFF), as well as 20 healthy control subjects. Motor-evoked potentials were elicited at rest or during a left- or right-hand response preparation in an instructed-delay choice reaction time task. Preparatory suppression was assessed by expressing amplitudes of motor potentials evoked during movement preparation relative to rest. Results Advanced PD patients exhibited a deficit in corticospinal suppression during movement preparation, limited to the responding hand (especially the most-affected), independently of STN-DBS. Significant links between preparatory suppression and clinical variables were found for least-affected hands only. Conclusion Our study provides evidence of altered corticospinal dynamics during movement preparation in advanced PD patients treated with STN-DBS. Consistent with results in earlier-stage patients, preparatory suppression deficits were limited to the responding hand and most pronounced on the most-affected side. STN-DBS did not restore this abnormality, which warrants further investigations into possible neuroanatomical sources of such corticospinal suppression, necessary to understand the consistent lack of this mechanism in PD patients. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT05209516 ### Funding Statement This work was supported by grants from Fonds Speciaux de Recherche (FSR; IONS-FSR16 DUQUE) and Action de Recherche Concertee Parkinson (ARC; M1.21303.001) of the Universite catholique de Louvain, the Belgian National Funds for Scientific Research (FRS-FNRS: MIS F.4512.14 and PDR T.0082.19), and Fondation Medicale Reine Elisabeth. During the research project, E.W. was a doctoral student supported by the L'Oreal-UNESCO For Women in Science program and the FRS-FNRS (1.A938.18). G.D. and C.Q. were postdoctoral fellows supported by the FRS-FNRS (1.B134.18, 1.B358.18). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Participants gave written informed consent, following a protocol approved by the Biomedical Ethics Committee of Saint-Luc University Hospital (Brussels, Belgium), in accordance with the Declaration of Helsinki. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data supporting the present study findings are available upon reasonable request to the authors. * CSE : corticospinal excitability DBS : deep brain stimulation DRT : dopamine replacement therapy FDI : first dorsal interosseous HC : healthy control M1 : primary motor cortex MDS-UPDRS-III : Movement Disorder Society Unified Parkinson’s Disease Rating Scale, Part III MEP : motor evoked potential PD : Parkinson’s disease STN : subthalamic nucleus TMS : transcranial magnetic stimulation