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Extraction of the EPP Component from the Surface EMG
Published on: December 16, 2009
Hypothetical membrane mechanisms in essential tremor.
Aasef G Shaikh1, Kenichiro Miura, Lance M Optican
1Department of Neurology, The Johns Hopkins University, Baltimore, MD, USA. ashaikh@dizzy.med.jhu.edu
Journal of Translational Medicine
|November 8, 2008
Summary
Essential tremor (ET) may stem from unstable neural circuits. Increased membrane excitability, particularly via Ih and IT currents, can cause oscillations mimicking ET symptoms.
Area of Science:
- Neuroscience
- Computational Neuroscience
- Movement Disorders
Background:
- Essential tremor (ET) is the most common movement disorder with unknown pathophysiology.
- Hypothesis: Increased membrane excitability in motor circuits contributes to ET pathogenesis.
- Proposed mechanism: Instability in reciprocally innervated circuits for ballistic movements leads to oscillations manifesting as tremor.
Purpose of the Study:
- To investigate the role of membrane excitability in ET pathogenesis.
- To simulate ET tremor using a computational model of neural circuits.
Main Methods:
- Recorded postural limb tremor in 22 ET patients.
- Developed a Hodgkin-Huxley type neuromimetic model of ballistic movement circuits.
- Incorporated hyperpolarization-activated cation current (Ih), low-threshold calcium current (IT), and inhibitory chloride currents.
- Modeled reciprocally innervated circuits with post-inhibitory rebound properties.
Main Results:
- Simulations replicated ET tremor characteristics when Ih was increased ~10-fold.
- Increased Ih and/or IT enhanced membrane depolarization and excitability.
- Modulating Ih and IT determined the frequency and amplitude of simulated oscillations.
- Altering other membrane conductances at physiological Ih levels did not reproduce ET tremor.
Conclusions:
- Simulations support the hypothesis linking increased membrane excitability in unstable circuits to ET.
- Up-regulation of Ih and IT currents effectively increased neural excitability in the model.
- Findings suggest novel experimental and clinical approaches for understanding and treating tremor disorders.
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