{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T17:08:48Z","timestamp":1782925728448,"version":"3.54.5"},"reference-count":94,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dutch Brain Foundation","award":["DR-2019-00311"],"award-info":[{"award-number":["DR-2019-00311"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background\/Objectives: Parkinson\u2019s disease (PD) and multiple sclerosis (MS) are neurological conditions that result in debilitating non-motor symptoms, such as anxiety and depression, which significantly reduce quality of life and often persist despite pharmacological treatment. As a result, effective alternative treatment strategies are needed. Exercise therapy\u2014particularly aerobic training\u2014has shown promise in alleviating non-motor symptoms, potentially through neuroplastic adaptations. However, traditional aerobic exercise is often time-consuming and monotonous, limiting long-term adherence. High-intensity interval training (HIIT) offers a time-efficient and potentially more engaging alternative, though its effects on non-motor symptoms in PD and MS remain understudied. Methods: This transdiagnostic randomized controlled trial will enroll 48 participants (24 PD, 24 MS) with clinically significant affective symptoms (hospital anxiety and depression scale [HADS] \u2265 8). The participants will be randomly assigned to one of three 8-week interventions: (1) HIIT, 5\u20136 intervals of 45 s of high-intensity cycling; (2) continuous aerobic training (CAT), 50 min of low-intensity cycling; (3) movement advice (MA), step goals, and physical education. The primary (affective symptoms) and secondary outcomes (cognition, fatigue, sleep, motor function) will be assessed at four time points: 4 and 1 weeks pre intervention, and 1 and 4 weeks post intervention. Weekly blood samples and pre\/post brain imaging will be collected to study biofluid and MRI measures for potential neuroplasticity. Linear mixed models will analyze the time and group effects. Discussion: This trial will assess whether HIIT can more effectively improve non-motor and motor symptoms in PD and MS than CAT or MA. A multimodal approach will explore both the clinical outcomes and underlying mechanisms, informing scalable and engaging rehabilitation strategies.<\/jats:p>","DOI":"10.3390\/brainsci15090945","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T16:42:21Z","timestamp":1756485741000},"page":"945","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["HIITing Anxiety and Depression in Parkinson\u2019s Disease and Multiple Sclerosis\u2014A Study Protocol of a Transdiagnostic Randomized Controlled Trial (HersenFIT)"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2458-2346","authenticated-orcid":false,"given":"Arianne S.","family":"Gravesteijn","sequence":"first","affiliation":[{"name":"Amsterdam UMC Location Vrije Universiteit Amsterdam, Rehabilitation Medicine, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Neuroscience, Neuroinfection & Inflammation, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Movement Sciences, Rehabilitation & Development, 1081 HZ Amsterdam, The Netherlands"},{"name":"MS Center Amsterdam, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc B.","family":"Rietberg","sequence":"additional","affiliation":[{"name":"Amsterdam UMC Location Vrije Universiteit Amsterdam, Rehabilitation Medicine, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Neuroscience, Neuroinfection & Inflammation, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Movement Sciences, Rehabilitation & Development, 1081 HZ Amsterdam, The Netherlands"},{"name":"MS Center Amsterdam, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6073-6250","authenticated-orcid":false,"given":"Vincent","family":"de Groot","sequence":"additional","affiliation":[{"name":"Amsterdam UMC Location Vrije Universiteit Amsterdam, Rehabilitation Medicine, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Neuroscience, Neuroinfection & Inflammation, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Movement Sciences, Rehabilitation & Development, 1081 HZ Amsterdam, The Netherlands"},{"name":"MS Center Amsterdam, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8997-7971","authenticated-orcid":false,"given":"Mark A.","family":"Hirsch","sequence":"additional","affiliation":[{"name":"Carolinas Rehabilitation, Department of Physical Medicine and Rehabilitation, Charlotte, NC 28203, USA"},{"name":"Wake Forest School of Medicine, Department of Orthopedic Surgery and Rehabilitation, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Vanbellingen","sequence":"additional","affiliation":[{"name":"Gerontechnology and Rehabilitation Group, University of Bern, 3012 Bern, Switzerland"},{"name":"VAMED Management & Services Schweiz AG, Research and Innovation, 8001 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6951-0952","authenticated-orcid":false,"given":"Richard T.","family":"Jaspers","sequence":"additional","affiliation":[{"name":"Amsterdam Movement Sciences, Rehabilitation & Development, 1081 HZ Amsterdam, The Netherlands"},{"name":"Laboratory of Myology, Department of Human Movement Science, Faculty of Behavioral and Movement Sciences, Location Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Movement Sciences, Tissue Function & Regeneration, 1081 HZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3111-1304","authenticated-orcid":false,"given":"Chris","family":"Vriend","sequence":"additional","affiliation":[{"name":"Amsterdam UMC Location Vrije Universiteit Amsterdam, Anatomy & Neurosciences, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam UMC Location Vrije Universteit Amsterdam, Psychiatry, De Boelelaan 1117, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Neuroscience, Compulsivity Impulsivity & Attention, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Neuroscience, Neurodegeneration, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6175-5357","authenticated-orcid":false,"given":"Wilma D. 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