HIITing Anxiety and Depression in Parkinson's Disease and Multiple Sclerosis-A Study Protocol of a Transdiagnostic Randomized Controlled Trial (HersenFIT).

Background/Objectives: Parkinson's 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-particularly aerobic training-has 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] ≥ 8). The participants will be randomly assigned to one of three 8-week interventions: (1) HIIT, 5-6 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.