rTMS of the SMA: a systematic review of clinical and fundamental approaches

Abstract The supplementary motor area (SMA) is a multifunctional brain region divided into two subregions: the pre-SMA and SMA-proper. Non-invasive brain stimulation was applied to both regions and reported to be successful in treating various neurological and psychiatric conditions. Here we systematically review studies involving repetitive transcranial magnetic stimulation (rTMS) applied over the SMA-proper/pre-SMA in healthy and clinical populations to leverage information about the future outlook of these regions neuromodulation. We included all original studies in English from the PubMed, Cochrane, and Scopus databases (PROSPERO ID - CRD42020141289). All studies were divided into two subgroups: (1) only healthy volunteers, (2) including patients. The following data were extracted from each study: sample characteristics, function investigated, rTMS parameters, the way of TMS coil targeting, and the primary outcome. The final review sample consisted of 129 studies; a similar amount of studies was performed in healthy (68 studies) and clinical (61 studies) populations. There were substantially more articles dedicated to SMA-proper, compared to pre-SMA stimulation, both in the healthy (44 vs 19) and clinical subgroup (53 vs 12). In the healthy subgroup, SMA-proper target was used primarily to modulate the motor function (65%), 25% of articles were dedicated to cognitive processes, 10% of articles reported only neurophysiological output such as functional connectivity. Interestingly, pre-SMA stimulation in healthy population was mostly done to modulate motor function (79%). At the same time, in the clinical population, SMA-proper target was primarily used for motor function modulation in neurological populations, in particular Parkinson's disease (>40%), while pre-SMA target was used predominantly in the psychiatric population of obsessive-compulsive disorder. Our review supports some preliminary conclusions about SMA-proper/pre-SMA as a highly promising target for NIBS in a wide range of neuropsychiatric conditions. However, more research, including EF modeling is needed to define interhemispheric and SMA/pre-SMA functional differences. Research Category and Technology and Methods Basic Research: 10. Transcranial Magnetic Stimulation (TMS) Keywords: SMA, pre-SMA, rTMS, non-invasive brain stimulation