Item

Abstract

Background: Despite its rapidly expanding application and fast-rising popularity, transcranial magnetic stimulation (TMS) is poorly understood physiologically. The lack of
knowledge on TMS physiology, together with the absence of an experimental platform on which various human TMS applications can be studied, developed and refined in
vivo at the neuronal level, block the exciting scientific and therapeutic potential of this non-invasive brain stimulation tool.
Methods: We developed a novel experimental platform that offers the direct in vivo electrophysiological access to TMS-evoked neuronal activities in the brain. The platform,
compatible with standard TMS stimulators and coils, attenuates a variety of TMSinduced artifacts in extracellular electrophysiology recordings and allows the recording to resume 0.8 - 1 ms after the onset of a variety of Tesla-level strong single or repetitive TMS stimuli. Furthermore, using rodents, a common laboratory animal model, we successfully replicated single-pulse TMS as is routinely used in humans and unveiled TMS-evoked neurons spiking activities in the layer V of the rodent primary motor cortex.
Results: The suprathreshold monophasic TMS stimulus reliably evoked unilateral activation of the forelimb muscles, evidenced by muscle unit action potentials recorded in the m. biceps bracchi (onset latency fi11 ms post-TMS). On the neuronal level, depending on the coil orientation, the cortical evoked multi-unit activity displayed 3 or 4 distinct phases of response: repetitive early excitation (< 6 ms) that is only visible under posterior-anterior (brain current) stimulation orientation, medium-latency excitation
(ca. 10-30 ms), long inhibition (ca. 35-200 ms) and rebound excitation (ca. 200-300 ms), all of which reveal striking relations to various well-known phenomena in human TMS
ranging from I-wave generation to late cortical disinhibition. Conclusions: The data obtained with our method depicted, for the first time, the neuronal picture of the classical single-pulse TMS that is widely used in research and clinical works. By bridging the gap between TMS stimuli and the behavioral outputs, the advance presented here facilitates a new level of insight into the TMS-brain interaction and is vital for developing and utilizing this non-invasive tool to purposefully explore and effectively treat the human brain.