NetworkStim · Evaluation of lesion network mapping as a technique to identify therapeutic targets for brain disorders

Disorders of the brain are a major source of disability, and place an enormous burden on society. Currently, many first-line treatmentsare non-specific, invasive, or cause side-effects. Non-invasive brain stimulation techniques, such as repetitive transcranial magneticstimulation (rTMS), have been shown to offer a safe treatment alternative, with rTMS first clinically approved for major depression in 2007. Unfortunately since then, translation to other disorders has been slow, mainly due to the lack of reliable methods to identify where in the brain to stimulate. Lesion network mapping (LNM) is a method recently introduced to address this problem. LNM works by mapping the connections of causative brain lesions, converging upon a small number of commonly connected locations in the brain. LNM has localised abnormal networks in over 40 different disorders. However, as yet no study has tested whether these networks respond to treatment. Therefore, the aim of this study is to conduct a clinical trial testing whether rTMS delivered to a specific site in the somatosensory cortex identified in our previously published LNM study (Corp et al., 2019, Brain) results in treatment benefit for cervical dystonia patients. Cervical dystonia is an ideal test case, as changes in abnormal neck movement symptoms are easily measurable, and this somatosensory location is on the surface of the brain, so easily reachable with rTMS. We will employ a randomised, sham-controlled, double-blind, crossover clinical trial, with 30 patients receiving 10 daily sessions of real and sham rTMS. Before and after the brain stimulation, we will collect clinical, behavioural, and physiological data to measure patients’ response to the intervention. Improvement in cervical dystonia symptoms after brain stimulation would serve as proof of the principle that LNM can effectively identify therapeutic targets, potentially unlocking safe and effective treatment protocols for a range of brain disorders.