The cortical motor threshold reflects microstructural properties of cerebral white matter

Transcranial magnetic stimulation (TMS) can be used to probe distinct aspects of excitability of the primary motor hand area (M1Hand). The motor threshold (MT) reflects the trans-synaptic excitability of corticospinal output neurons. The MT corresponds to the minimal intensity at which TMS evokes a contralateral motor response. Here, we employed diffusion-weighted imaging (DWI) to examine whether inter-individual differences in MT of the left and right M1Hand, an index of cortical excitability, are associated with variations in fractional anisotropy (FA), an index of white matter microstructure. Resting and active MT showed an inverse linear relationship with regional FA values in large bihemispheric clusters, including the white matter underlying primary motor, premotor and posterior prefrontal cortices, as well as the genu of the internal capsule, cerebral peduncles and corpus callosum. The linear increase in FA with cortical excitability as indexed by the MT remained significant after controlling for differences in handedness or coil-cortex distance. The posterior limb of the internal capsule, where fast-conducting corticospinal fibres from M1Hand pass through, showed only a weak linear relationship between FA and MT. The FA measurements show that a high level of corticospinal excitability is associated with a higher fibre coherence in large parts of cerebral white matter. The higher FA values in the white matter beneath premotor and motor cortices may reflect a structural property of cortico-cortical connections that renders M1Hand more susceptible to TMS-induced trans-synaptic excitation of the corticospinal fibres and may account for the inverse linear relationship between MT and FA.