Investing in Innovation: 2016-2017 Grants

There have been reports that marijuana can be effective in decreasing the amount of tics in Tourette Syndrome (TS). Marijuana would be difficult for most people to use on a daily basis because its main active compound, THC, causes the high associated with the drug and affects the ability to work or go to school. Another common compound found in marijuana called cannabidiol has been isolated, and because it does not cause the high associated with THC it is more easily tolerated and can be taken daily. We plan on studying this drug and whether or not it can decrease tic frequency in adults with TS.

In children with Tourette Syndrome (TS), tics, impulsive actions, and compulsions may result partly from difficulties in the brain’s systems for “stopping.” We propose to learn more about and improve this stopping by using transcranial magnetic stimulation and electrical measurements in muscles to compare the brain’s stopping system in children with and without TS. We will then use a new training method called “Selective Suppression with Real-Time Feedback” to evaluate how well children can learn to activate their stopping system. Ultimately we aim to find out whether this method can help children gain better control over their unwanted actions.

Children with Tourette Disorder often have additional emotional and behavioral problems which may cause more problems than their tics. Currently, psychological treatments generally take on one disorder at a time that can be time consuming, impractical and expensive. The goal of this project is to develop and test a psychological treatment for children and adolescents to manage the many symptoms that may accompany tics – including problems controlling emotions, acting out, reacting without thinking, and trouble making good
decisions

Individuals with Persistent Tic Disorders (PTDs) often experience sleep problems, including difficulties falling asleep and staying asleep. Sleep is regulated partly by the circadian system, a near-24-hour biological clock. Prior research suggests the presence of circadian disruption (body temperature, and cortisol dysregulation) in PTDs. Such disruption may impact tic severity and quality of life. Therefore, this study will evaluate circadian rhythms in 20 adults with PTDs and 20 healthy control participants through assessment of endogenous melatonin, circadian phase preference, and 24-hour rest/activity rhythms. Findings may aid our understanding of the nature of tic symptom variability, and help enhance existing treatments.

Comprehensive Behavioral Intervention for Tics (CBIT) is a safe, effective treatment for Tourette Syndrome (TS). Unfortunately, there remain insufficient numbers of trained behaviorists to meet the needs of most TS patients. In this study, we will develop a home-based behavioral treatment instructional video and guide. We will then compare reductions in tic severity using this parent-administered therapy to that achieved with traditional face-to-face treatment by an experienced psychologist. Evidence of effectiveness of home-based, parent-directed therapy would enable direct frontline treatment for all individuals affected with tics

Advances in reading people’s genetic code have helped in understanding rare genetic disorders. Our gene sequencing program identified rare gene sequence variations in members of a family with TS across multiple generations. We used this genetic
information to engineer mice with identical changes in their normal gene sequence, and will be testing those mice to observe behavioral and anatomic brain changes that might mimic those in the TS affected family. These mice will establish an animal model of TS that could be instrumental in understanding the causes of TS and developing strategies for treating TS.

Tourette Syndrome is thought to arise from dysfunction of neural circuits in the basal ganglia, a set of nuclei that control the selection of motor actions. Although prominent symptoms of Tourette Syndrome include aberrant orofacial and vocal actions,
how the basal ganglia normally control these actions remains poorly understood. Therefore, we are mapping the basal ganglia circuit pathways that control orofacial and vocal musculature and determining how neurons in these pathways appropriately activate target muscles. Our findings will enable more specific circuit studies of Tourette symptoms with the ultimate goal of identifying more specific therapeutics for orofacial and vocal symptoms.

We know that several medications can effectively reduce TS symptoms. We also know that a behavioral treatment called
Comprehensive Behavioral Intervention for Tics, or CBIT, can work very well; whether it’s delivered face-to-face or remotely via video conferencing technology. Most of what we know about these treatments comes from tightly-controlled studies, which are
scientifically very sound, but may not reflect how things work in typical clinic settings. So, in this study, we will be comparing these different treatments in a hospital tic clinic under “real-world” conditions. We hope to learn what treatments patients prefer to try, both as first- and second-line treatments. We also hope to begin to learn about how well these treatments work compared to one another in this clinic setting.

Through collaboration with TS genetics investigators throughout the world, the TAA International Consortium for Genomics (TAAICG)
seeks to advance the knowledge of genetic susceptibilities that underlie Tourette Syndrome and related disorders.