Brain morphometry is not associated with non-motor outcomes after deep brain stimulation in Parkinson's disease

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an established therapy in advanced Parkinson's disease (PD). Motor and non-motor outcomes, however, show considerable inter-individual variability. Morphometry-based metrics have recently received increasing attention to predict treatment effects. As evidence for the prediction of non-motor outcomes is limited, we sought to investigate the association between metrics of voxel-based morphometry and short-term non-motor outcomes following STN-DBS in this prospective open-label study. 49 PD patients underwent structural MRI and a comprehensive clinical assessment at preoperative baseline and 6-month follow-up. Voxel-based morphometry was used to assess associations between cerebral volume and non-motor outcomes corrected for multiple comparisons using a permutation-based approach. We replicated existing results associating atrophy of the superior frontal cortex with subpar motor outcomes. Non-motor outcomes, however, were not associated with morphometric features, limiting its use as a marker to inform patient selection and holistic preoperative counselling. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement PAL was supported by the SUCCESS-Program of the Philipps-University of Marburg, the Stiftung zur Foerderung junger Neurowissenschaftler, and the Prof. Klaus Thiemann Foundation in the German Society of Neurology. WS was supported by the Koeln Fortune Program/Faculty of Medicine, University of Cologne and reports no financial relationships with commercial interests. STJ was funded by the Prof. Klaus Thiemann Foundation and the Brandau-Laibach-Foundation, outside of the submitted work. MS has received honoraria from Bial, Britannia and Medtronic. JNPS funded by the Cologne Clinician Scientist Program (CCSP)/Faculty of Medicine/ University of Cologne; and by the German Research Foundation (DFG, FI 773/15-464 1). AS reports no financial disclosures. AG reports no financial disclosures. VVV reports compensation for contributions to advisory boards and congresses for Medtronic, Boston Scientific, and Livanova. GRF serves as an editorial board member of Cortex, Neurological Research and Practice, NeuroImage: Clinical, Zeitschrift fuer Neuropsychologie, DGNeurologie, and Info Neurologie & Psychiatrie; receives royalties from the publication of the books Funktionelle MRT in Psychiatrie und Neurologie, Neurologische Differentialdiagnose, and SOP Neurologie; receives royalties from the publication of the neuropsychological tests KAS and Koepps; received honoraria for speaking engagements from Deutsche Gesellschaft fuer Neurologie (DGN) and Forum fuer medizinische Fortbildung FomF GmbH. JE reports no financial disclosures. MK was funded by the KoelnFortune program of the Medical Faculty of the University of Cologne and reports no financial relationships with commercial interests. AR received funding from the National Institute for Health and Care Research (NIHR), the Clinical Research Network (CRN) South London, and grant funding from the International Parkinson and Movement Disorders Society (MDS). AA received compensation for consultancy and speaker-related activities from UCB, Boehringer Ingelheim, Ever Pharma, General Electric, Britannia, AbbVie, Kyowa Kirin, Zambon, Bial, Theravance Biopharma, Jazz Pharmaceuticals, Roche, Medscape. He receives research support from Bial, Lundbeck, Roche, Angelini Pharmaceuticals, Horizon 2020 Grant 825785, Horizon 2020 Grant 101016902, Ministry of Education University and Research (MIUR) Grant ARS01 01081, Cariparo Foundation, Movement Disorders Society for NMS Scale validation. He serves as consultant for Boehringer-Ingelheim for legal cases on pathological gambling. KA has received honoraria for educational meetings, travel and consultancy from Medtronic, St. Jude Medical and Boston Scientific. PMM received honoraria from the International Parkinson and Movement Disorder Society (IPMDS) for management of the Clinical Outcome Assessment Program. CG reports no financial disclosures. KRC received grants (IIT) from Britannia Pharmaceuticals, AbbVie, UCB, GKC, EU Horizon 2020, Parkinson's UK, NIHR, Parkinson's Foundation, Wellcome Trust, Kirby Laing Foundation, MRC; royalties or licenses from Oxford (book), Cambridge publishers (book), MAPI institute (KPPS, PDSS 2); consulting fees, support for attending meetings or travel, and participated on data safety monitoring board or advisory board for AbbVie, UCB, GKC, Bial, Cynapsus, Lobsor, Stada, Zambon, Profile Pharma, Synovion, Roche, Therevance, Scion, Britannia, Acadia, 4D Pharma, and Medtronic; and served as a committee chair for MDS (unpaid) and EAN (unpaid). LT received payments as a consultant for Medtronic Inc. and Boston Scientific and received honoraria as a speaker on symposia sponsored by Bial, Zambon Pharma, UCB Schwarz Pharma, Desitin Pharma, Medtronic, Boston Scientific, and Abbott. The institution of LT, not LT personally, received funding by the German Research Foundation, the German Ministry of Education and Research, and Deutsche Parkinson Vereinigung. JCB is funded by the Else Kroener-Fresenius-Stiftung (2022 EKES.23) and receives funding by the German Research Foundation (Project ID 431549029-C07). HSD was funded by the EU Joint Programme Neurodegenerative Disease Research (JPND), the Prof. Klaus Thiemann Foundation in the German Society of Neurology, the Felgenhauer Foundation, the KoelnFortune program of the Medical Faculty of the University of Cologne and has received honoraria by Everpharma, Kyowa Kirin, Bial, Oruen, and Stadapharm. ### 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: The ethics committee of the University of Cologne gave approval for this work. 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 All data produced in the present study are available upon reasonable request to the authors