Sensorimotor gating in Tourette Syndrome

Grant Type
Grant Year
Institution Location
Institution Organization Name
University of California
Investigators Name
Swerdlow, Neal, MD, PhD

Several neuropsychiatric disorders are linked in a phenomenological dimension by an inability to inhibit or “gate” intrusive, undesired behaviors, thoughts or sensory information, and are linked in an anatomical dimension by dysfunction in related neural substrates. For example, patients with Huntington’s Disease (HD) are unable to inhibit undesired choreiform movements, and patients with Obsessive Compulsive Disorder (OCD) can’t inhibit intrusive, meaningless thoughts and images. Patients with Tourette Syndrome (TS) are unable to inhibit premonitory urges or undesired tics or vocalizations. Substantial evidence suggests that these disorders of impaired “gating” are all associated with dysfunction within interconnected cortico-striatopallido-thalamic circuitry. It is possible to quantify sensorimotor gating in psychiatric patients, and to study the neurobiology of gating processes in cross-species models. One measure of sensorimotor gating, “prepulse inhibition” (PP), is the normal inhibition of the startle reflex that occurs when the startling stimulus is preceded 30-500 msec by a weak click of “prepulse”. PPI of the eye blink component of startle is studied in humans, and PPI of whole body startle is studied in laboratory animals, using identical stimulus parameters across species. Importantly, PPI, is impaired or absent in patients with disorders of defective “gating”, including schizophrenia, HD and OCD, but is intact in other patients, including those with affective disorders or Post Traumatic Stress Disorder. In animals, the “primary” startle circuit consists of five neurons connecting the auditory nerve with the spinal motoneuron, but this circuit is modulated by forebrain structures. Specifically, we have demonstrated that PPI is modulated by circuitry connecting portions of the limbic system, basal ganglia and pontine reticular formation that have been implicated in the pathophysiology of TS. Since sensorimotor gating as measured by PPI is controlled by brain substrates that are implicated in the pathophysiology of TS, it is possible that impaired gating in TS patients might be quantified using the PPI paradigm. Measures of PPI in TS patients might thus help identify the pathophysiology of impaired gating in these patients, and might also serve as important phenotypic markers for genetic linkage analyses. We will complete a detailed study of PPI and related “gating” measures in TS patients in concert with a structured clinical assessment of these patients. Findings will be compared with data from ongoing studies in laboratory animals and in patients with OCD and HD, and may be used as the basis for future family studies of sensorimotor gating in TS probands. Neal R. Swerdlow, M. D., Ph.D. University of California, San Diego, San Diego, CA Award $23,584 Tourette Association of America Inc. – Research Grant Award 1993