Physiological Analysis of Cortico-Basal Ganglia Loops during Repetitive Movements

Grant Type
Grant Year
Institution Location
Institution Organization Name
Investigators Name
Ninokura, Yoshihisa, PhD

Motor tics are significant diagnostic hallmarks of Tourette Syndrome (TS) and are still of unknown origin. The behavioral deficits in TS are thought to reflect dysfunction of neuronal circuitry including cortico-basal ganglia loops interconnecting the frontal cortex and striatum. For normal movement control, these cortico-basal ganglia loops are thought to be critical for sequential movement performance and also for the acquisition of repetitive movement sequences. However, little information is available about the simultaneous activity of neurons in the cortex and basal ganglia during the performance of motor sequences. Therefore, it is difficult to understand the mechanisms underlying the appearance of repetitive tics such as those occurring in TS. Most of our movements occur as parts of movement sequences. Great efforts have been made to study the neural basis of sequential movement plans and movement execution, but information about how these neural activities are coordinated across brain sites is still lacking. Such coordination could be critical for successful movement performance as well as for terminating movement sequences. The repetitive tics of TS could represent dysfunction of such multi-site coordination, or the lack of specific neural signals serving as “stop” signals, or both. I propose a series of recording experiments to determine the nature of such coordinated activity in the brain of monkeys as they perform repetitive visually guided arm-reaching movements characterized by different degrees of repetitiveness. My goal is to elucidate the activity patterns in cortico-basal ganglia loops that occur differentially during highly repetitive behaviors. These experiments will provide fundamental information about the activity of brain structures already strongly implicated in the genesis of TS and will address the critical question of what activity occurs in cortico-basal ganglia circuits when repetitive actions are performed as compared to when the actions performed are random. Although these studies do not focus on the repetitive actions of tics in TS patients, they nonetheless should greatly enhance our understanding of the neural signature of repetitive actions and the neural signals that stop them. Ultimately, this information could be crucial to developing rational treatments for this disorder. Yoshihisa Ninokura Ph.D. Massachusetts Institute of Technology, Cambridge, Massachusetts Award: $40,000 This study is underwritten through the generosity of Randi Zemsky Tourette Association of America Inc. – Research Grant Award 2006-2007