Combining Transcranial Magnetic Stimulation and Deep Brain Stimulation: Current Knowledge, Relevance and Future Perspectives

: Deep brain stimulation (DBS) has emerged as an invasive neuromodulation technique for the treatment of several neurological disorders, but the mechanisms underlying its effects remain partially elusive. In this context, the application of Transcranial Magnetic Stimulation (TMS) in patients treated with DBS represents an intriguing approach to investigate the neurophysiology of cortico-basal networks. Experimental studies combining TMS and DBS that have been performed so far have mainly aimed to evaluate the effects of DBS on the cerebral cortex and thus to provide insights into DBS's mechanisms of action. The modulation of cortical excitability and plasticity by DBS is emerging as a potential contributor to its therapeutic effects. Moreover, pairing DBS and TMS stimuli could represent a method to induce cortical synaptic plasticity, the therapeutic potential of which is still unexplored. Furthermore, the advent of new DBS technologies and novel treatment targets will present new research opportunities and prospects to investigate brain networks. However, the application of the combined TMS-DBS approach is currently limited by safety concerns. In this review, we sought to present an overview of studies performed by combining TMS and DBS in neurological disorders, as well as available evidence and recommendations on the safety of their combination. Additionally, we outline perspectives for future research by highlighting knowledge gaps and possible novel applications of this approach.