Neuroengineering at the Cortex: Neural Tract Selection and Electrical Reconstruction of TMS Motor Effects

The origin and tracts of motor activity elicited by transcranial magnetic stimulation (TMS) are important for understanding neuromodulatory properties of TMS and for designing appropriate models of TMS effects. Stimulation above the motor cortex in humans produces distinct cortex mediated effects, whereas murine models of TMS have been limited by a lack of stimulus focality relating to coil size and anatomical variations of the corticospinal tract. We sought to overcome these limitations by comparing lateralized, intensity-dependent motor activity produced by TMS with motor activity produced by focal bipolar stimulation of the motor cortex at varying depths. Our findings indicate a strong cortical component of murine TMS that can be replicated by electrical stimulation above and inside (but not below) the motor cortex. Our bipolar electrical stimulation protocol also approximated the ability of paired-pulse TMS to elicit long-interval intracortical inhibition and the ability of theta-burst repetitive TMS to mediate long-term depression of motor circuits. It should additionally be noted that at high stimulus amplitudes, TMS produced a second motor evoked potential preceding the cortical signal that was not replicated by high-intensity electrical stimulation. These results suggest that lateralized murine TMS can elicit motor responses via the corticospinal tract, with possible signal spreading to deep brain structures at high intensities. We also concluded that bipolar electrical stimulation of the motor cortex is a reliable method for focally approximating the effects of TMS on cortex mediated motor activity.