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Journal of the Royal Society Interface (1)
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Chacron, Maurice J. (1)
Cloutier, Mathieu (1)
García, Míriam R. (1)
Middleton, Richard H. (1)
Pearlmutter, Barak A. (1)
Wellstead, Peter (1)
Wellstead, Peter E. (1)
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A Slow Axon Antidromic Blockade Hypothesis for Tremor Reduction via Deep Brain Stimulation
García, Míriam R.
Pearlmutter, Barak A.
Middleton, Richard H.
Chacron, Maurice J.
Parkinsonian and essential tremor can often be effectively treated by deep brain stimulation. We propose a novel explanation for the mechanism by which this technique ameliorates tremor: a reduction of the delay in the relevant motor control loops via preferential antidromic blockade of slow axons. The antidromic blockade is preferential because the pulses more rapidly clear fast axons, and the distribution of axonal diameters, and therefore velocities, in the involved tracts, is sufficiently long-tailed to make this effect quite significant. The preferential blockade of slow axons, combined with gain adaptation, results in a reduction of the mean delay in the motor control loop, which serves to stabilize the feedback system, thus ameliorating tremor. This theory, without any tuning, accounts for several previously perplexing phenomena, and makes a variety of novel predictions.
The control systems structures of energy metabolism
Journal of the Royal Society Interface
The biochemical regulation of energy metabolism (EM) allows cells to modulate their energetic output depending on available substrates and requirements. To this end, numerous biomolecular mechanisms exist that allow the sensing of the energetic state and corresponding adjustment of enzymatic reaction rates. This regulation is known to induce dynamic systems properties such as oscillations or perfect adaptation. Although the various mechanisms of energy regulation have been studied in detail from many angles at the experimental and theoretical levels, no framework is available for the systematic analysis of EM from a control systems perspective. In this study, we have used principles well known in control to clarify the basic system features that govern EM. The major result is a subdivision of the biomolecular mechanisms of energy regulation in terms of widely used engineering control mechanisms: proportional, integral, derivative control, and structures: feedback, cascade and feed-forward control. Evidence for each mechanism and structure is demonstrated and the implications for systems properties are shown through simulations. As the equivalence between biological systems and control components presented here is generic, it is also hypothesized that our work could eventually have an applicability that is much wider than the focus of the current study.
control theory; energy metabolism; metabolic regulation; systems biology
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