IMPAIRED PREPULSE INHIBITION OF ACOUSTIC AND TACTILE STARTLE RESPONSEIN PATIENTS WITH HUNTINGTONS-DISEASE

The corpus striatum serves a critical function in inhibiting involunta ry, intrusive movements. Striatal degeneration in Huntington's disease results in a loss of motor inhibition, manifested by abnormal involun tary choreiform movements. Sensorimotor inhibition, or ''gating'', can be measured in humans using the startle reflex: the startle reflex is normally inhibited when the startling stimulus is preceded 30-500 ms earlier by a weak prepulse. In the present study, prepulse inhibition (PPI) was measured in patients with Huntington's disease to quantify a nd characterise sensorimotor gating. Compared with age matched control s, patients with Huntington's disease exhibit less PPI. Startle gating deficits are evident in patients with Huntington's disease when start le is elicited by either acoustic or tactile stimuli. Even with stimul i that elicit maximal PPI in normal subjects, patients with Huntington 's disease exhibit little or no PPI, and their pattern of startle gati ng does not show the normal modulatory effects usually elicited by cha nging the prepulse interval or intensity. Startle amplitude and habitu ation and latency facilitation are largely intact in these patients, a lthough reflex latency is significantly slowed. In patients Huntingon' s disease, startle slowing correlates with cognitive impairment measur ed by the dementia rating scale, and with the performance disruptive e ffects of interference measured by the Stroop test. These findings doc ument a profound disruption of sensorimotor gating in patients with Hu ntingon's disease and are consistent with preclinical findings that id entify the striatum and striatopallidal GABAergic efferent circuitry a s critical substrates for sensorimotor gating of the startle reflex.