The Movement Disorder Society

MDS Abstract of the 16th International Congress of Parkinson's Disease and Movement Disorders, Volume 27,
June 2012 Abstract Supplement

Movement Disorders 2012
Dublin, Ireland June 17-21, 2012.


A functional mechanism for deep brain stimulation in Parkinson's disease: The slow axon blockade hypothesis

Garcia,  M.R., Pearlmutter,  B.A., Wellstead,  P.E., Verwoerd,  M., Middleton,  R.H.

Objective:

To determine the functional mechanisms of Deep Brain Stimulation for the treatment of parkinsonian tremor.

Background:

Deep brain stimulation (DBS) can ameliorate essential and parkinsonian tremor. The detailed mechanism by which this is achieved is unclear, but clues to the mechanism may lie in the known destabilising influence of time delays upon closed-loop systems.

Methods:

We hypothesise that DBS tends to stabilise the system and reduce tremor oscillations by reducing time delays in motor control system feedback loops. We posit that the reduction is associated with a partial blockade of axonal pathways by antidromic activation, with the blockade being less complete for axons with higher propagation velocities. The inverse relationship between blockade effectiveness and propagation velocity would be due to the blocking pulses clearing the axon faster when their velocity is higher, leaving a larger fraction of the time for signalling activity.

Results:

Numeric calculations of effective DBS frequencies given the length of the involved pathways, the known distribution of axonal diameters, and the known relationship between axonal diameter and velocity, are consistent with clinical observations. A simplified model of the motor control loop [1] and a simple model capturing relevant features of the parkinsonian pathology in specific neuronal circuits [2] both exhibit changes under simulated DBS that agree with several heretofore-unexplained clinical observations. This theory also makes a variety of strong testable predictions.

Conclusions:

The Slow Axon Blockade Hypothesis is a simple idea, not easily tuned, which naturally accounts for a variety of known features of DBS not easily explained by other theories.

Keywords :

Deep brain stimulation (DBS),Motor control,Parkinsonism,Tremors: Treatment

To cite this abstract, please use the following information:
Garcia, M.R., Pearlmutter, B.A., Wellstead, P.E., Verwoerd, M., Middleton, R.H.; A functional mechanism for deep brain stimulation in Parkinson's disease: The slow axon blockade hypothesis [abstract]. Movement Disorders 2012;27 Suppl 1 :491