Effects of DBS on sensorimotor processes

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DESCRIPTION (provided by applicant) Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders. Reaction time task (RTt), a behavioral test measuring the sensorimotor reaction, is impaired in Parkinsonian patients. Impairment of RTt was also found in the animal model of PD. Lesion of the STN is able to restore the reaction time response that is disrupted by nigrostriatal dopamine lesion in the rat. Deep brain stimulation (DBS) of subthalamic nucleus (STN) has been used increasingly in the clinic to alleviate Parkinsonian syndromes (PS) during the past decade. Lack of behavioral model of rats for DBS research has hampered efforts to understand the neural mechanisms underlying the therapeutic effects of DBS. This proposal will combine advanced chronic, multiple-channel, single unit recording technique with unique DBS methods in the rat to study the neural responses in nigrostriatal dopamine lesioned rats performing RTt. An aim will be to use DBS to restore RT performance as a test of voluntary movement. Sixty-four recording electrodes will be implanted into the motor cortex, the globus pallidus, the STN, and the substantia nigra pars reticulata (SNr) and 4 pair of stimulation electrodes into the STN and SNr. Extracellular spike activity will be recorded simultaneously during RTt. After control sessions are completed, lesion of nigrostriatal dopamine system will be made by injection of 6-OHDA into both sides of striatum. The behavioral and electrophysiologic results after dopamine lesion will be compared with that obtained from the control condition to reveal the effects of dopamine depletion. High frequency stimulation (HFS) of STN and SNr will then be applied during RTt to counteract the adverse effects of dopamine depletion on RTt. This study will illustrate the neural responses mediating different aspects of RTt during the pathophysiological development of PD. The hypothesis that DBS of STN and SNr will restore normal neural processing in the basal ganglia thalamocortical circuit will be tested by analyzing the single and ensemble neural responses during behaviorally effective DBS. The aim of this proposal is to understand the fundamental neural mechanisms underlying the effects of DBS on PD. Incorporating the DBS into the well understood pathophysiological basal ganglia-thalamocortical network model and thus being able to restore normal network function to treat PD is the ultimate goal of this study. This research will be done primarily at Peking University in China as an extension of NIH grant R01-NS43441.