Integrative Examination of Neurobehavioral Mechanisms in Tic Suppression

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DESCRIPTION (provided by applicant): This K23 Career Development Award is designed provide the training needed for the PI to achieve her long-term career goal of conducting independent, programmatic research on the neurobehavioral mechanisms underlying tics and repetitive behavior problems associated with cortico-striatal-thalamo-cortical (CSTC) circuit dysfunction. Consistent with this goal, the proposed study will focus on the neurobehavioral mechanisms underlying tic suppression in a sample of youth with chronic tics. This award builds on the PI's emerging expertise in tic and obsessive-compulsive spectrum disorders and experimental psychopathology methods to study behavioral mechanisms that impact tic expression. This award will extend the PI's research to include integrated study of behavioral and neurobiological mechanisms in tic suppression. Additional mentored training will ensure that the PI acquires the technical skills and advanced theoretical and scientific knowledge needed to develop, lead, and contribute to integrative, interdisciplinary disease mechanism research in mental disorders associated with CSTC circuit dysfunction. The highly structured training plan will enable the PI to obtain skills and knowledge in the following areas: 1) CSTC neurocircuitry and neuroanatomy, 2) transcranial magnetic stimulation (TMS) methodology, 3) use of magnetic resonance imaging (MRI) data to guide TMS navigation, 4) ethical and safe use of TMS in child psychopathology research, and 5) collaborative obsessive- spectrum neuroscience research. Training and research will be guided by an expert mentorship team comprised of leading scientists in the fields of psychiatry, psychology, and neurology. The research plan of this K23 award will examine the relationship between supplementary motor area (SMA) activation and tic suppression using an innovative methodology that combines 1 hz repetitive TMS (rTMS) vs. sham rTMS with an established behavioral tic suppression paradigm. Chronic tics are a disabling neuropsychiatric symptom and the most common movement disorder in children. The mechanisms underlying tic suppression are poorly understood but thought to involve an interaction between biological and contextual factors. SMA is a cortical node of the CSTC circuit that plays a key role in facilitating context-dependent motor output and is hyperactive in those with tics. The current study will probe the role of SMA activity in tic suppression using TMS, a non-invasive procedure that allows for the temporary modulation of cortical regions. Aim 1 will address whether inhibition of SMA excitability leads to changes in baseline tic frequencies, voluntary tic suppression, and tic suppressability in the presence of suppression-contingent reinforcement. Aim 2 will explore whether premonitory urge intensity changes in conjunction with inhibition of SMA excitability. This will be the first study to directly examine the relationsip between SMA functioning, tic suppression, and premonitory urge intensity. Results will refine our understanding of brain-context relationships involved in tic suppression and may have implications for the broader understanding of neurobehavioral processes involved in the suppression of other unwanted repetitive behaviors.