Computer Modeling of Motor Cortex Stimulation: How to Connect to Clinical Practice?

Computer modeling of Motor Cortex Stimulation: How to connect to clinical practice?

J.R. Buitenjweg, L. Manola, J. Holsheimer, P. H. Veltink MCS for suppression of chronic pain

• Clinical Practice – Intra-operative positioning • Bipolar stimulation • Anode pre-central (MC) • Cathode post-central (S1) – Post-operative analgesic effect • Bipolar stimulation • Cathode pre-central • Mechanisms – Pre or Postcentral Gyrus Involved? – Antidromic Thalamic Activation? – … which fibers are activated? • Mathemathical Modeling – Volume conduction – Neural Activation Neural Fiber Orientations in the Cortex

I II sulcus III

IV motor V cortex

VI white matter

• Fibers are oriented both Parallel and Perpendicular to Cortical laminae • Cortical laminae are curved: varying orientation to MCS electrode Modeling Motor Cortex Stimulation

• Volume Conduction • Neural fibers • Electrode configurations Influence of CSF layer thickness

• Average thickness CSF: 3.1±0.6 mm1) • Lead thickness: 2 mm • dCSF (under electrode): 1.1±0.6mm

1) Estimated from n=6 T2 weighted MRI density profiles (Manola et al., 2005) Activation of fibers (dCSF 1.1 mm)

• Electrode positions affect order of activation • Actual fiber diameters unkown (distributions) • Thresholds scaled by variations dSCF

(Manola et al., 2007) Simulation Results

• Efferent E1 can only be E1 activated anodally E2

• Efferent E3 can only be sulcus activated cathodally

• Efferent E2 can be E3 motor activated both cathodally cortex and anodally

• Afferent A is preferentially stimulated white cathodally matter Main Message from Modeling • Electrode Polarity and electrode Position influence the response of cortical neural elements to stimuli. • Cathodal and Anodal stimulation activate different groups of neural elements • In Bipolar stimulation both cathode and anode are active electrodes Coupling to Clinical practice • dCSF and fiber diameters still unkown, hence thresholds may vary widely • Cathodal vs Anodal threshold differences not reflected in clinical MEP resonses (although D- and I-waves do differ) • Ergo: Multiple scenario’s may still explain clinical results. Future Work on MCS modeling • Goal: limit the number of possible scenario’s explaining MCS effects • Morphometrical analysis of PCG fibers – fiber diameters and distributions • Documentation of MCS procedures – Electrode positions and dCSF – Peroperative stimulation results Morphometrical analysis PCG • Hans Feierabend (LUMC, Leiden) • Post-mortem: 5 brains, 10 samples PCG from each • 2-3 mm of PCG is stained and analysed – Coupes in multiple directions – Area of each fiber measured, radius calculated afterwards (assumed circular) • Recently some younger brains are added

a b

Sampling areas of 20700 _m2 of primary motor cortex (touluidine blue section perpendicular to the pial surface): a. in white matter b. + 1000 _m into cortex c. + 2000 _m into cortex c Distribution of myelinated fibers in cortical layers (from white matter to pial surface)

1.5 Density oflarger myelinated fibers in part L3 of the primary motor cortex (N727) 10 Density of myelinated fibers

) > 5 µm

(whole range) in part L3 of 2 m

) > 6 µm µ

2 the primary motor cortex (N727)

m 8 1.0 > 7 µm µ > 8 µm 6 > 9 µm > 10 µm

4 0.5 > 11 µm D[f] (fibers/1000 Dens[f] (fibers/1000 2

0.0 0 0 250 500 750 1000 1250 1500 1750 2000 2250 2500 0 250 500 750 1000 1250 1500 1750 2000 2250 2500

WPdistance (µm) wpdist (µm) Documentation of MCS procedures • Clinical observability of activations – Perpendicular (E) fibers: MEP responses – Parallel (A) fibers: ? • Obstacle for clinical validation studies: – Limited # clinical centers – Limited # patients / center – Combined multicenter action desired! Clinical data from MCS implantations • Clinical centers involved: – Nantes: Jean Paul Nguyen and team – Nijmegen: Tjemme Beens and team • Systematic documentation procedure – Pre operative imaging – Per-operative mapping of MEP responses – Storage of electrode positions (Neuronav) – Post operative stimulation adjustment • Analysis + – Effects of dCSF on MEP responses – Effects of electrode positions on MEP responses – Electrode positions and post-op pain reduction Thank you