Transcranial ultrasound stimulation induces white matter plasticity in the human corticospinal tract

Non-invasive methods to causally modulate human white matter plasticity have proved elusive. In vitro and in vivo studies indicate that myelinated axons are sensitive to mechanical perturbations from ultrasound, providing a mechanistic rationale for targeting white matter tracts with ultrasound neuromodulation. Here, we demonstrate that transcranial ultrasound stimulation (TUS) induces site-specific plasticity in the human corticospinal tract. In a within-subject study, 15 healthy adults received 5 Hz patterned TUS targeted at the left corticospinal tract at the level of the superior internal capsule. The homologous tract in the opposite hemisphere and the ipsilateral motor cortex were targeted as comparison conditions to confirm site specificity. Left corticospinal tract TUS increased corticomotor excitability and intracortical facilitation, whereas left motor cortex TUS reduced intracortical inhibition. Diffusion tractography showed the magnitude of TUS-induced plasticity scaled with individual differences in white matter microstructure (fractional anisotropy) and ultrasound orientation in relation to the tract. These findings provide causal evidence of white matter plasticity in the human corticospinal tract and establish TUS as a tool for non-invasive neuromodulation of white matter tracts in health and disorders of white matter.