HIGH FREQUENCY REPETITIVE SENSORY STIMULATION IN HEALTHY! SUBJECTS AND DYSTONIA

This thesis describes a series of studies involving both healthy subjects and patients with dystonia, in which the mechanisms of inhibitory plasticity have been explored with the use of a novel non-invasive brain stimulation technique, namely High-Frequency Repetitive Sensory Stimulation (HF-RSS), to understand how inhibitory mechanisms contribute to the pathogenesis of dystonia. To this aim, several “preliminary” and parallel experiments have been conducted to fully characterize the neurophysiological abnormalities in dystonia and the physiological changes induced by HF-RSS in healthy subjects. Thus, I have explored: 1. The neurophysiological correlates of abnormal somatosensory temporal discrimination in cervical dystonia, linking this behavioural abnormality with defective inhibitory mechanisms within the sensory cortex; 2. The behavioural consequences of HF-RSS in healthy subjects in terms of somatosensory temporal discrimination, showing that this technique can be in fact used as a novel non-invasive brain stimulation protocol in order to reversibly improve somatosensory temporal discrimination; 3. The neurophysiological mechanisms by which the observed behavioural improvement occurs after HF-RSS in healthy subjects. Thus, the improvement of somatosensory temporal discrimination is mostly driven by an enhancement of inhibitory processes occurring within the primary sensory cortex, a phenomenon known as inhibitory plasticity; 4. Whether HF-RSS could ameliorate inhibitory processes in cervical dystonia and, in turn, lead to an improvement of somatosensory temporal discrimination. It is here shown that patients showed a paradoxical response to such a stimulation protocol, suggestive of defective inhibitory plasticity as one of the main mechanisms contributing to the pathogenesis of dystonia. These results contribute to the understanding of the pathophysiology of dystonia, opening a novel window for future research and possibly novel treatments. Moreover, these results widened the understanding relative to this novel type of non-invasive brain stimulation that can be theoretically used for the study of other disorders where central inhibitory processes are thought to be defective.