The Role of Non-Invasive Brain Modulation in Identifying Disease Biomarkers for Diagnostic and Therapeutic Purposes in Parkinsonism

Over the past three decades, substantial advancements have occurred in non-invasive brain stimulation (NIBS). These developments encompass various non-invasive techniques aimed at modulating brain function. Among the most widely utilized methods today are transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES), which include direct- or alternating-current transcranial stimulation (tDCS/tACS). In addition to these established techniques, newer modalities have emerged, broadening the scope of non-invasive neuromodulation approaches available for research and clinical applications in movement disorders, particularly for Parkinson's disease (PD) and, to a lesser extent, atypical Parkinsonism (AP). All NIBS techniques offer the opportunity to explore a wide range of neurophysiological mechanisms and exert influence over distinct brain regions implicated in the pathophysiology of Parkinsonism. This paper's first aim is to provide a brief overview of the historical background and underlying physiological principles of primary NIBS techniques, focusing on their translational relevance. It aims to shed light on the potential identification of biomarkers for diagnostic and therapeutic purposes, by summarising available experimental data on individuals with Parkinsonism. To date, despite promising findings indicating the potential utility of NIBS techniques in Parkinsonism, their integration into clinical routine for diagnostic or therapeutic protocols remains a subject of ongoing investigation and scientific debate. In this context, this paper addresses current unsolved issues and methodological challenges concerning the use of NIBS, focusing on the importance of future research endeavours for maximizing the efficacy and relevance of NIBS strategies for individuals with Parkinsonism.