Thalamic Regulation of Basal Ganglia Circuitry Thalamostriatal System: A Potential Target for Surgical Therapy in Tourette Syndrome (2nd year)

Grant Type
Basic
Grant Year
2007-2008
Institution Location
GA
Institution Organization Name
Emory University
Investigators Name
Smith, Yoland, PhD

Tourette Syndrome (TS) is a chronic neuropsychiatric disorder which is characterized by a variety of involuntary movements, including motor and vocal tics and stereotyped behaviors. Neurobehavioral disturbances, such as obsessive compulsive behaviors and the symptoms of attention deficit hyperactive disorder (ADHD) are also associated with TS. The pathophysiology of TS is not well understood. For some, drug treatments are only moderately effective, which has led to a search for new treatment options for people with TS. Neurosurgical approaches are being increasingly used for the treatment of medication-resistant symptoms of several movement disorders. These surgeries involve either electrolytic lesion or deep brain stimulation (DBS) of target nuclei. Of these operations, DBS is currently preferred because of its reversibility and the fact that its effects can be adjusted to the patient’s specific needs. In TS, DBS has involved a number of brain targets, including the medial thalamus, internal globus pallidus (GPi) and other areas of the brain. These interventions have been reported to reduce both the quantity and intensity of tics, and may also treat the psychiatric symptoms of the disease. Importantly, the mechanisms of action of DBS are unknown. Knowing how DBS works would enable us to maximize the anti-tic effects of thalamic DBS, and, in a larger sense might help us better understand the pathophysiology of this condition. With TSA funding, we have begun to examine the effects of electrical stimulation of a specific structure in the thalamus named the centromedian/parafascicular complex (CM/Pf ) in the monkey striatum. Data obtained so far are promising, and highlight the complexity of electrophysiologic and neurochemical changes that are induced by thalamic stimulation. Over the coming year, we propose to expand these studies and characterize the roles of various neurotransmitter receptors in mediating the effects of CM/Pf on striatal activity. Furthermore, we will examine the effects of CM/Pf stimulation on other basal ganglia nuclei. We hope that this research will bring us closer to a better understanding of the effects of thalamic DBS in TS, and may result in a data driven rational approach to selecting DBS targets and stimulation parameters in the future. Yoland Smith, Ph.D., ThomasWichmann, M.D. Emory University Atlanta, GA Award: $75,000 (2nd Year) Tourette Association of America Inc. – Research Grant Award 2007-2008