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

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.