Essential tremor (ET) is a common and often progressive neurological disease with a prevalence of around 4% after the age of 40 years. More than 90% of ET patients who seek medical attention report disability. In the work setting, 15-25% of ET patients retire prematurely, and 60% choose not to seek promotion because of increased motor variability. Although ET can affect the head, voice, legs and trunk in 10-40% of cases, it affects variability of the upper limbs and hands in at least 95% of the cases. We therefore focus our research on variability during tasks involving the hand while contacting an object and producing force, because this basic task is performed during daily activities such as eating and drinking, and is negatively affected by ET. Specifically, we are interested in the interaction of visual feedback and motor variability. The proposed studies will test the novel central hypothesis that lowering the gain of visual feedback of motor output will reduce the variability of ET patients close to that of healthy adults. We plan to pursue this hypothesis because: 1) recent fMRI evidence from our laboratory indicates that visual cortex activity is increased in ET; 2) abnormal visual cortex activity is positively correlated with increased force variability; and 3) our preliminary data from individuals with ET demonstrates that reducing the gain of visual feedback substantially improves force variability. The experiments in this renewal will use multimodal imaging and electrophysiology from brain to muscle to investigate the extent of improvement, and exactly how low gain feedback reduces motor variability in ET. Our preliminary data using task-based fMRI, high-density electroencephalography (EEG), deep brain stimulation of the thalamus, and multi-motor unit oscillations provides insight into the physiology supporting the central hypothesis.
Aim 1 tests the central hypothesis using fMRI, which has superb spatial resolution, across the visual cortex, cerebellum, thalamus, and motor cortex.
Aim 2 tests the central hypothesis using high- density EEG and cutting-edge 3D cortical imaging analyses, which has high temporal resolution, across visual cortex and motor cortex.
Aim 3 tests the central hypothesis by using deep brain stimulation to stimulate the thalamus, which is a key structure that facilitates visually-guided movement, while measuring multi-motor unit action potentials of hand muscles. This collection of systems neuroscience techniques represents an innovative approach to maximize both spatial and temporal resolution and reveal novel mechanisms from brain to muscle underpinning how low gain visual feedback reduces motor variability in ET.

Public Health Relevance

Essential tremor (ET) is a common and often progressive neurological disease with a prevalence of around 4% after the age of 40 years. We will determine if reducing the gain of visual feedback provided during motor performance can alter the variability of hand grip force in ET. We will also examine the underlying physiology for these effects using several different systems neuroscience techniques. We will provide a better understanding of the pathophysiology of ET using multimodal imaging and electrophysiology and motor unit action potentials. The outcome of these studies will provide critical advances to inform biomedical engineers and rehabilitation specialists how to design displays for improving performance in ET.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS058487-06A1
Application #
8877742
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Chen, Daofen
Project Start
2007-01-01
Project End
2020-03-31
Budget Start
2015-07-01
Budget End
2016-03-31
Support Year
6
Fiscal Year
2015
Total Cost
Indirect Cost
Name
University of Florida
Department
Physiology
Type
Sch Allied Health Professions
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
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