The Thalamostriatal System: A Potential Target for Surgical Therapy in Tourette Syndrome

Grant Type
Basic
Grant Year
2006-2007
Institution Location
GA
Institution Organization Name
Emory University
Investigators Name
Smith, Yoland, PhD

Tourette Syndrome (TS) is a chronic neuropsychiatric disorder with an onset in childhood and is characterized by motor and vocal tics. The pathophysiology of TS is poorly understood, but there is good evidence that it involves abnormal regulation of the basal ganglia, a region of the brain important for the control of motor, emotional and cognitive behaviors. Over the last few years, there has been tremendous interest in the use of neurosurgical techniques for the treatment of movement disorders. In particular, deep brain stimulation (DBS) procedures are now used more and more in patients with Parkinsonism, Dystonia and other conditions. Some of these surgical interventions may be effective in TS, and there are a few reports of a reduction in TS symptoms. A suggested target for the surgical treatment of TS is a nuclear complex of the thalamus named the centromedian-parafascicular (CM/Pf) nucleus. Although it has long been known that this brain region is tightly connected with the basal ganglia, the exact role of CM/Pf remains poorly understood. For these reasons, the mechanisms underlying the beneficial effects of DBS in the CM/Pf of Tourette patients are unclear. Because the pathophysiology of TS likely involves abnormal functioning of the basal ganglia, we believe that an in-depth analysis of the electrophysiological, neurochemical, and structural changes induced in the basal ganglia by CM/Pf stimulation will help us better understand the mechanisms that mediate the beneficial effects of thalamic DBS in TS. As a starting point, we propose to examine the effects of electrical stimulation of CM/Pf on the activity of neurons, and transmitter levels in the basal ganglia in monkeys using electrophysiologic and anatomic techniques. Changes in the location, structure and expression of neurotransmitters and receptors in various basal ganglia nuclei will be examined as well. The results from these studies will not only help to develop a better understanding of the effects of thalamic stimulation in TS, but also may result in a more rational approach to the selection of stimulation targets and stimulation parameters in patients with TS. Yoland Smith, Ph.D., Thomas Wichmann, M.D., Adriana Galvan, Ph.D. Emory University, Atlanta, Georgia Award: $74,927 Tourette Association of America Inc. – Research Grant Award 2006-2007