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Background: Disorders of consciousness (DOC), i.e., unresponsive wakefulness syndrome (UWS) or vegetative state (VS) and minimally conscious state (MCS), are conditions that can arise from severe brain injury, inducing widespread functional changes. Given the damaging implications resulting from these conditions, there is an increasing need for rehabilitation treatments aimed at enhancing the level of consciousness, the quality of life, and creating new recovery perspectives for the patients. Music may represent an additional rehabilitative tool in contexts where cognition and language are severely compromised, such as among DOC patients. A further type of rehabilitation strategies for DOC patients consists of Non-Invasive Brain Stimulation techniques (NIBS), including transcranial electrical stimulation (tES), affecting neural excitability and promoting brain plasticity., Objective: We here propose a novel rehabilitation protocol for DOC patients that combines music-based intervention and NIBS in neurological patients. The main objectives are (i) to assess the residual neuroplastic processes in DOC patients exposed to music, (ii) to determine the putative neural modulation and the clinical outcome in DOC patients of non-pharmacological strategies, i.e., tES(control condition), and music stimulation, and (iii) to evaluate the putative positive impact of this intervention on caregiver's burden and psychological distress., Methods: This is a randomised cross-over trial in which a total of 30 participants will be randomly allocated to one of three different combinations of conditions: (i) Music only, (ii) tES only (control condition), (iii) Music + tES. The music intervention will consist of listening to an individually tailored playlist including familiar and self-relevant music together with fixed songs; concerning NIBS, tES will be applied for 20 minutes every day, 5 times a week, for two weeks. After these stimulations two weeks of placebo treatments will follow, with sham stimulation combined with noise for other two weeks. The primary outcomes will be clinical, i.e., based on the differences in the scores obtained on the neuropsychological tests, such as Coma Recovery Scale-Revised, and neurophysiological measures as EEG, collected pre-intervention, post-intervention and post-placebo., Discussion: This study proposes a novel rehabilitation protocol for patients with DOC including a combined intervention of music and NIBS. Considering the need for rigorous longitudinal randomised controlled trials for people with severe brain injury disease, the results of this study will be highly informative for highlighting and implementing the putative beneficial role of music and NIBS in rehabilitation treatments., Trial Registration: ClinicalTrials.gov identifier: NCT05706831, registered on January 30, 2023., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Spaccavento et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)