The goal of this project is to advance the understanding of movement disorders pathophysiology through studies of basal ganglia and cortical local field potentials (LFPs) in humans. The LFP represents synchronized sub- and supra-threshold activity in presynaptic terminals and postsynaptic neurons. Recent studies of subthalamic nucleus (STN) LFPs in Parkinson's disease (PD) produced a novel hypothesis: that parkinsonian bradykinesia is due to excessive basal ganglia synchronized oscillatory activity in the beta frequency range (13-30 Hz), and that suppression of beta oscillations is the mechanism for the effectiveness of STN deep brain stimulation (DBS). However, this framework leaves unanswered questions. Can the beta oscillation hypothesis be confirmed by comparison to subjects without movement disorders? Are excessive beta oscillations unique to PD, or are they associated with other movement disorders of basal ganglia origin? Are abnormal beta oscillations present in motor cortex as well, reflecting a network property of the basal ganglia-thalamocortical (BGTC) circuit? Here, we address these questions by comparing primary motor (M1) and primary sensory (S1) cortex LFPs in patients with a basal ganglia disorder (PD and primary dystonia), with two comparison groups without basal ganglia pathology (essential tremor (ET) and epilepsy). Movement disorders patients are studied while undergoing awake placement of DBS electrodes. Epilepsy patients are studied while undergoing inpatient video monitoring. We hypothesize that PD and dystonia both are characterized by broad beta band cortical activity which distinguishes these disorders from ET and from subjects without movement disorders. Our second major goal is to understand BGTC oscillations in primary dystonia, which has been less studied than PD. Our approach is simultaneous recording of STN and cortical LFPs in M1 and S1. We hypothesize: (1) Dystonic patients have an excess of high beta (21-30) and low gamma (30-55 Hz) oscillations in the STN during voluntary movement, while PD patients have predominant low beta (13- 20 Hz) activity, particularly at rest. 2.) Similar patterns are seen in M1 and S1, and in STN-cortical coherence. 3.) Movement related abnormalities in dystonia will be reproduced under conditions in which sensory feedback is activated. The novel features of this proposal are the use of electrocorticography in movement disorders, the introduction of a new target, STN, into the study of dystonia, and the analysis of cortex-basal ganglia interactions through simultaneous LFP recording in both areas. The proposed work should expand the framework for the """"""""oscillation hypothesis"""""""" of PD to include the other major movement disorders, improve the rationale for choice of stimulation frequencies in DBS and could provide a basis for cortically based therapies for PD and dystonia.

Public Health Relevance

The goal of this study is to improve the understanding of abnormal brain electrical activity in persons with movement disorders such as Parkinson's disease and dystonia. Patients are studied while undergoing routine neurosurgical treatment of their disorder by implantation of brain stimulators. Knowledge gained in this study may lead to simpler surgical therapies than those now available, and may help neurologists improve existing treatments by understanding how to program implanted brain stimulators more effectively.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Clinical Neuroscience and Neurodegeneration Study Section (CNN)
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Sieber, Beth-Anne
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Panov, Fedor; Levin, Emily; de Hemptinne, Coralie et al. (2017) Intraoperative electrocorticography for physiological research in movement disorders: principles and experience in 200 cases. J Neurosurg 126:122-131
Cole, Scott R; van der Meij, Roemer; Peterson, Erik J et al. (2017) Nonsinusoidal Beta Oscillations Reflect Cortical Pathophysiology in Parkinson's Disease. J Neurosci 37:4830-4840
Swann, Nicole C; de Hemptinne, Coralie; Maher, Ryan B et al. (2016) Motor System Interactions in the Beta Band Decrease during Loss of Consciousness. J Cogn Neurosci 28:84-95
Wang, Doris D; de Hemptinne, Coralie; Miocinovic, Svjetlana et al. (2016) Subthalamic local field potentials in Parkinson's disease and isolated dystonia: An evaluation of potential biomarkers. Neurobiol Dis 89:213-22
Miocinovic, Svjetlana; de Hemptinne, Coralie; Qasim, Salman et al. (2015) Patterns of Cortical Synchronization in Isolated Dystonia Compared With Parkinson Disease. JAMA Neurol 72:1244-51
Rowland, Nathan C; De Hemptinne, Coralie; Swann, Nicole C et al. (2015) Task-related activity in sensorimotor cortex in Parkinson's disease and essential tremor: changes in beta and gamma bands. Front Hum Neurosci 9:512
de Hemptinne, Coralie; Swann, Nicole C; Ostrem, Jill L et al. (2015) Therapeutic deep brain stimulation reduces cortical phase-amplitude coupling in Parkinson's disease. Nat Neurosci 18:779-86
Swann, Nicole C; de Hemptinne, Coralie; Aron, Adam R et al. (2015) Elevated synchrony in Parkinson disease detected with electroencephalography. Ann Neurol 78:742-50
de Hemptinne, Coralie; Ryapolova-Webb, Elena S; Air, Ellen L et al. (2013) Exaggerated phase-amplitude coupling in the primary motor cortex in Parkinson disease. Proc Natl Acad Sci U S A 110:4780-5
Shimamoto, Shoichi A; Ryapolova-Webb, Elena S; Ostrem, Jill L et al. (2013) Subthalamic nucleus neurons are synchronized to primary motor cortex local field potentials in Parkinson's disease. J Neurosci 33:7220-33

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