Tourette syndrome (TS) and disorders involving tic are highly prevalent and socially embarrassing. There are a group of TS sufferers with motor and vocal tics that are resistant to medication and behavioral intervention. Deep brain stimulation (DBS) has emerged as a highly efficacious treatment option for addressing motor and vocal tics in a select group of appropriately screened cases. The proposed research will directly address the important knowledge gaps in TS physiology and TS DBS. These gaps include a need to characterize the pathophysiological signals related to tics and the modulation of physiology by DBS therapy.
In Aim 1, we will correlate individual tic expression with local fiel potential (LFP) activity in the human centromedian (CM) thalamic nucleus region and precentral gyrus (motor cortex) using next generation DBS devices capable of chronic LFP recordings. We will also study thalamocortical network interactions leading to tics. Our preliminary data from two subjects have revealed that low-frequency activity in the CM thalamus and beta rhythm suppression in the motor cortex correlate with the occurrence of tics, and that these features can be differentiated from the neural correlates of voluntary movements.
In Aim 2, we will determine how LFP physiology changes following DBS therapy and clinical improvement. Our preliminary data from five subjects, treated with bilateral centromedian (CM) thalamic region DBS, (from recently completed NIH R34 and R21 grants) demonstrated the presence of both a measurable clinical effect and quantifiable physiological changes (decreases in low frequency power). Understanding how DBS modulates brain activity to reduce TS symptoms, could provide a neuromarker to guide clinical programming and potentially facilitate faster clinical relief. The overarching goal of the proposed project will be to generate the physiological dataset required to fill these knowledge gaps and to move the field toward responsive stimulation.

Public Health Relevance

The proposed project is relevant to public health because it will increase and accelerate the understanding and the research into the physiological underpinnings of Tourette Syndrome, and how tics can be modulated by electrical stimulation. This could lead to personalized therapies and will make an important positive impact on the quality of life of patients suffering from this disorder. Thus, the proposed research is relevant t the mission of the NIH NINDS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS096008-05
Application #
9967137
Study Section
Clinical Neuroscience and Neurodegeneration Study Section (CNN)
Program Officer
Morris, Jill A
Project Start
2016-07-01
Project End
2021-06-30
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
5
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Florida
Department
Neurosciences
Type
Schools of Medicine
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Vedam-Mai, Vinata; Rodgers, Cooper; Gureck, Ashley et al. (2018) Deep Brain Stimulation associated gliosis: A post-mortem study. Parkinsonism Relat Disord 54:51-55
van Wouwe, N C; Pallavaram, S; Phibbs, F T et al. (2017) Focused stimulation of dorsal subthalamic nucleus improves reactive inhibitory control of action impulses. Neuropsychologia 99:37-47
Loza, Carlos A; Shute, Jonathan B; Principe, Jose C et al. (2017) A marked point process approach for identifying neural correlates of tics in Tourette Syndrome. Conf Proc IEEE Eng Med Biol Soc 2017:4375-4378
Burciu, Roxana G; Hess, Christopher W; Coombes, Stephen A et al. (2017) Functional activity of the sensorimotor cortex and cerebellum relates to cervical dystonia symptoms. Hum Brain Mapp 38:4563-4573
Ramirez-Zamora, Adolfo; Okun, Michael S (2016) Deep brain stimulation for the treatment of uncommon tremor syndromes. Expert Rev Neurother 16:983-97
Ritaccio, Anthony L; Williams, Justin; Denison, Tim et al. (2016) Proceedings of the Eighth International Workshop on Advances in Electrocorticography. Epilepsy Behav 64:248-252
Rossi, P Justin; Opri, Enrico; Shute, Jonathan B et al. (2016) Scheduled, intermittent stimulation of the thalamus reduces tics in Tourette syndrome. Parkinsonism Relat Disord 29:35-41
Shute, Jonathan B; Okun, Michael S; Opri, Enrico et al. (2016) Thalamocortical network activity enables chronic tic detection in humans with Tourette syndrome. Neuroimage Clin 12:165-72