Gray and white matter integrity influence TMS signal propagation: a multimodal evaluation in cocaine-dependent individuals.

Transcranial magnetic stimulation (TMS) can stimulate cortical and subcortical brain regions. However, in order to reach subcortical targets, intact monosynaptic connections are required. The goal of this investigation was to evaluate the contribution of white matter integrity and gray matter volume to frontal pole TMS-evoked striatal activity in a large cohort of chronic cocaine users. 49 cocaine users received single pulses of TMS to the frontal pole while BOLD data were acquired - a technique known as interleaved TMS/fMRI. Diffusion tensor imaging and voxel-based morphometry were used to quantify white matter integrity and gray matter volume (GMV), respectively. Stepwise regression was used to evaluate the contribution of clinical and demographic variables to TMS-evoked BOLD. Consistent with previous studies, frontal pole TMS evoked activity in striatum and salience circuitry. The size of the TMS-evoked response was related to fractional anisotropy between the frontal pole and putamen and GMV in the left frontal pole and left ACC. This is the first study to demonstrate that the effect of TMS on subcortical activity is dependent upon the structural integrity of the brain. These data suggest that these structural neuroimaging data types are biomarkers for TMS-induced mobilization of the striatum.