Neurofeedback from the supplementary motor area for Tourette Syndrome - Abstract The proposed project is a clinical trial to confirm the efficacy of a real-time fMRI neurofeedback intervention that involves training adolescents with Tourette Syndrome to control a region of their supplementary motor area (SMA) believed to be involved in tic generation. The intervention involves providing feedback on SMA activity to participants while they practice regulating the region. They are cued to up-regulate and to down-regulate the area at different times and encouraged to try mental strategies for both up-regulating and down-regulating that have the potential to improve their symptoms. For up-regulation, this includes engaging in mental imagery of complex motor activities, or doing mentally demanding cognitive tasks, in order to co-opt the relevant neural circuitry for tasks other than tic generation. For down-regulation, this includes imagining relaxing scenarios that tend to be associated with reduced stress levels and an associated reduction in tic severity. This intervention was previously compared with a yoked sham control intervention in a small crossover design study that yielded very promising results: large clinical effects were observed and the groups showed differences in their ability to regulate the SMA during neurofeedback. Here we attempt to confirm that preliminary finding of efficacy in a larger, purely randomized design that includes follow-up of participants, and critically, employs a different form of control condition. In the proposed study, the control group will be trained via neurofeedback to control a region of their visual association cortex that is believed to be unrelated to their symptoms. This control region will be defined for each control subject in a manner that ensures it is not functionally connected to their SMA. By using this new form of control condition, this study ensures that the intervention has been tested against two of the most rigorous forms of control conditions used in clinical applications of real-time fMRI neurofeedback (yoked sham and training on a control region). Given that the different types of control conditions rule out different kinds of confounds, this is the most rigorous approach to testing this intervention: if results are promising, they cannot be dismissed as an artifact of the kind of control condition used. In short, with the proposed clinical trial, we aim to confirm the clinical efficacy of this new intervention, and to verify that it is acting via the hypothesized mechanism of action (enhancement of control over the SMA via neurofeedback). In addition, effects of the intervention on resting state functional connectivity patterns will be examined to better inform our understanding of the network changes induced by the training.
