Effects of frequency-dependent membrane capacitance on neural excitability.
Abstract
<h4>Objective</h4>Models of excitable cells consider the membrane specific capacitance
as a ubiquitous and constant parameter. However, experimental measurements show that
the membrane capacitance declines with increasing frequency, i.e., exhibits dispersion.
We quantified the effects of frequency-dependent membrane capacitance, c(f), on the
excitability of cells and nerve fibers across the frequency range from dc to hundreds
of kilohertz.<h4>Approach</h4>We implemented a model of c(f) using linear circuit
elements, and incorporated it into several models of neurons with different channel
kinetics: the Hodgkin-Huxley model of an unmyelinated axon, the McIntyre-Richardson-Grill
(MRG) of a mammalian myelinated axon, and a model of a cortical neuron from prefrontal
cortex (PFC). We calculated thresholds for excitation and kHz frequency conduction
block, the conduction velocity, recovery cycle, strength-distance relationship and
firing rate.<h4>Main results</h4>The impact of c(f) on activation thresholds depended
on the stimulation waveform and channel kinetics. We observed no effect using rectangular
pulse stimulation, and a reduction for frequencies of 10 kHz and above using sinusoidal
signals only for the MRG model. c(f) had minimal impact on the recovery cycle and
the strength-distance relationship, whereas the conduction velocity increased by up
to 7.9% and 1.7% for myelinated and unmyelinated fibers, respectively. Block thresholds
declined moderately when incorporating c(f), the effect was greater at higher frequencies,
and the maximum reduction was 11.5%. Finally, c(f) marginally altered the firing pattern
of a model of a PFC cell, reducing the median interspike interval by less than 2%.<h4>Significance</h4>This
is the first comprehensive analysis of the effects of dispersive capacitance on neural
excitability, and as the interest on stimulation with kHz signals gains more attention,
it defines the regions over which frequency-dependent membrane capacitance, c(f),
should be considered.
Type
Journal articleSubject
NeuronsCell Membrane
Animals
Humans
Differential Threshold
Electric Capacitance
Action Potentials
Neural Conduction
Models, Neurological
Computer Simulation
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https://hdl.handle.net/10161/23851Published Version (Please cite this version)
10.1088/1741-2560/12/5/056015Publication Info
Howell, Bryan; Medina, Leonel E; & Grill, Warren M (2015). Effects of frequency-dependent membrane capacitance on neural excitability. Journal of neural engineering, 12(5). pp. 56015-56015. 10.1088/1741-2560/12/5/056015. Retrieved from https://hdl.handle.net/10161/23851.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Warren M. Grill
Edmund T. Pratt, Jr. School Distinguished Professor of Biomedical Engineering
Our research employs engineering approaches to understand and control neural function.
We work on fundamental questions and applied development in electrical stimulation
of the nervous system to restore function to individuals with neurological impairment
or injury.
Current projects include:• understanding the mechanisms of and developing advanced
approaches to deep brain stimulation to treat movement disorders, • developing
novel approaches to peripheral nerve e
Bryan Howell
Assistant Research Professor in the Department of Biomedical Engineering
My lab studies implantable and wearable devices for treating neurological impairment,
namely with deep brain stimulation (DBS) and transcranial electrical stimulation (tES).
Projects evolve through theoretical and preclinical stages of development, combining
biophysical and dynamic causal modeling, medical imaging, and device prototyping,
to test new concepts and strategies for these neurotechnologies. Noninvasive studies
on tES are conducted in tissue phantoms and healthy human subjects in-hous
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