Cleveland Clinic Lerner College of Medicine/Cwru
Grant: $372,171 - National Institutes of Health - Sep. 26, 2009
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Award Description: The overall aim of this project is to clarify the relationship between neuronal activity in the internal segment of the globus pallidus (GPi) and the development, phenotypic distribution and severity of dystonic movements in patients with primary generalized (PGD) and cervical dystonia (CD). Three fundamental questions will be addressed: 1) What are the physiological characteristics of neurons in the basal ganglia in patients with PGD and CD? 2) Is there a relationship between those physiological characteristics (e.g. mean discharge rate, somatosensory response properties, or the number of cells with bursting or power at low oscillatory frequencies) and clinical measures of dystonia severity (Burke Fahn Marsden Dystonia Rating Scale for PGD and Toronto Western Spasmodic Torticollis Rating Scale for CD)? and 3) Is there a difference in the relative proportion and distribution of neurons in the GPi that demonstrate these dystonic characteristics between patients with PGD and those with CD? Neural and force control data will be gathered simultaneously in the operating room during microelectrode mapping of the GPi as part of deep brain stimulation surgery. Neuronal, EMG and force control data will be collected from 48 (24 PGD and 24 CD) dystonia patients. Specific Aims 1 and 2 are focused on determining the relationship between neuronal activity (i.e. mean discharge rate, pattern, oscillatory activity and somatosensory response properties) within the GPi and the severity of PGD and CD, respectively. The final phase of Aims 1 and 2 will be to compare the neural activity within the GPi in patients with PGD and CD. This comparison will allow us to determine if PGD and CD patients have common alterations in neural activity or if each type of dystonia has its own unique pathophysiology. In Specific Aim 3, patients will perform a force-tracking motor task during the recording of neural activity within GPi. Motor performance will be objectively quantified using biomechanical measures. The simultaneous collection of neural and motor data is unique and will clarify the relationship between neuronal activity within the GPi of PGD and CD patients and their specific impairments in the control of muscle forces, in particular the scaling and focusing of force. Identifying specific physiological characteristics associated with dystonia, determining the spatial segregation of affected neurons in PGD and CD and understanding the specific motor impairments of each will refine current surgical strategies and may lead to new surgical approaches to relieve dystonic symptoms. PUBLIC HEALTH RELEVANCE: Dystonia is a movement disorder characterized by sustained muscle contractions that lead to twisting, repetitive movements and abnormal postures. The lack of a suitable animal model for dystonia has slowed the progress of understanding what causes dystonia and impeded the advancement of using surgical interventions, such as deep brain stimulation, for treatment. We propose to study the two most common types of dystonia: primary generalized dystonia (PGD) and cervical dystonia (CD). The proposed study will, for the first time, simultaneously record neural activity from structures within the basal ganglia in human dystonia patients while they perform a motor task. We will determine the relationship between changes in neuronal activity and the severity of dystonia. Identifying specific physiological characteristics associated with dystonia and determining the spatial segregation of affected neurons in PGD and CD will provide the rationale for improving current surgical strategies and the development of future therapeutic approaches.
Project Description: As Defined in the Award Description field
Jobs Summary: NA (Total jobs reported: 0)
Project Status: Not Started
This award's data was last updated on Sep. 26, 2009. Help expand these official descriptions using the wiki below.
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