Motor threshold in transcranial magnetic stimulation: the impact of white matter fiber orientation and skull-to-cortex distance

Abstract

The electrophysiology of transcranial magnetic stimulation (TMS) of motor cortex is not well understood. In this study, we investigate several structural parameters of the corticospinal tract and their relation to the TMS motor threshold (MT) in 17 subjects, with and without schizophrenia. We obtained structural and diffusion tensor MRI scans and measured the fractional anisotropy and principal diffusion direction for regions of interest in the corticospinal tract. We also measured the skull-to-cortex distance over the left motor region. The anterior-posterior trajectory of principle diffusion direction of the corticospinal tract and skull-to-cortex distance were both found to be highly correlated with MT, while fractional anisotropy, age and schizophrenia status were not. Two parameters-skull-to-cortex distance and the anterior component of the principle diffusion direction of the corticospinal tract as it passes the internal capsule-are highly predictive of MT in a linear regression model, and account for 82% of the variance observed (R2 = 0.82, F = 20.27, P < 0.0001) in measurements of MT. The corticospinal tract's anterior-posterior direction alone contributes 13% of the variance explained.

Figure 1

Sample illustrations of ROI placement details. Panel A illustrates the posterior limb of the internal capsule (PIC) identified at the level of the foramen of Monro. Panel B shows ROI placement around the cerebral peduncle (CP). Finally, Panels C–E show sample axial, sagittal and coronal sections of the hand cortex ROI (HK) illustrated on top of the fractional anisotropy (FA) map used to generate it. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Figure 2

The fiber bundle representing corticospinal tract, tracked with seeds at CP and PIC (white) and the constrained portion used to define CST ROI (blue) in two views. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Figure 3

Orientation of the principle diffusion direction (PDD) as defined in this paper. Macroscopically, PDD is a unit vector uniquely defined by three coordinates (PDD‐X, PDD‐Y, PDD‐Z) that define an mean trajectory of white matter fibers in a specific region of interest (here portion of the corticospinal tract). This figure illustrates the putative mechanism of neuronal excitation in TMS and the importance of axonal direction and bend at a microscopic level in the generation of motor evoked potentials (The illustration was modified by permission from Ruohonen and Ilmoniemi [2002].) [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Figure 4

Linear regression plot with MT as dependent variable and SCD and PIC PDD‐Y as independent variable.