A Slow Axon Antidromic Blockade Hypothesis for Tremor Reduction via Deep Brain Stimulation

Abstract

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.

Direct Functional Connectivity between the Thalamus (Vim) and the Contralateral Motor Cortex: Just a Single Case Observation or a Common Pathway in the Human Brain?

“…The minuscule (~0.37 ms) inter-hemispheric time lag in the fronto-central CERs is in keeping with the idea of the thalamus being at equal time distance from various cortical areas through changes in the degree of myelination of white matter tracts [10,13]. This finding, to our knowledge, is the first evidence in vivo supporting the idea of isochronous synchronisation between two delaycoupled oscillators through a third mediating element at equal distance in time from the outer elements [14].…”

“…The distance between the subthalamic nucleus and the cortex and the thalamus and the cortex is about 6 and 5 cm respectively and this could explain the similarities with our findings. The short chronaxie used during DBS and the very short latency CERs (onset latency at 1.4 ms in our patient) are pointing towards this activity being generated by stimulation of myelinated axons connecting the thalamus to the cortex [10]. As the degree of myelination of white matter tracts connecting the thalamus to the cortex appears to be variable, some of the slower conducting axons could be functionally blocked during stimulation at 80 Hz.…”

“…As the degree of myelination of white matter tracts connecting the thalamus to the cortex appears to be variable, some of the slower conducting axons could be functionally blocked during stimulation at 80 Hz. The CERs recorded at this frequency could be generated by the fastest conducting connections [10].…”

Features of structure of nerve motor endings in the tongue of normal and dehydrated rats

“…Нейротрофическое влияние мотонейрона на мышечные волокна в значительной степени зависит от системы аксонного транспорта. На это указывает ряд исследований при его фармакологической блокаде (García et al, 2013). Поэтому деструктуризация аксоплазмы при дегидратации следует расценивать как фактор, который ослабляет нейротрофический контроль на мембрану мышечного волокна.…”

Basal Forebrain Deep Brain Stimulation Impacts the Regulation of Extracellular Vesicle Related Proteins in the Rat Brain

“…Advantages of DBS include the direct and spatially specific modulation of brain activity as well as the controlled manner of stimulation and reversibility of effects. Despite the long history of DBS, its underlying principles and mechanisms remain incompletely understood (49–51). A large number of studies have reported the release of neurotransmitters induced by DBS in brain areas that are relevant for movement disorders.…”