Enhancing neuronal plasticity through intracranial theta burst stimulation in the human sensorimotor cortex.

The progress of therapeutic neuromodulation greatly depends on improving stimulation parameters to most efficiently induce neuroplasticity effects. Intermittent Theta Burst stimulation (iTBS), a form of electrical stimulation that mimics the natural brain activity patterns, has shown efficacy in inducing such effects in animal studies and rhythmic Transcranial Magnetic Stimulation (rTMS) studies in humans. However, little is known about the potential neuroplasticity effects of iTBS applied through intracranial electrodes in humans which could have implications for deep brain stimulation therapies. This study characterizes the physiological effects of cortical iTBS in the human cortex and compare them with single pulse alpha stimulation, another frequently used paradigm in rTMS research. We applied these stimulation paradigms to well-defined regions in the sensorimotor cortex which elicited contralateral hand or arm muscle contractions during electrical stimulation mapping in epilepsy patients implanted with intracranial electrodes. Treatment effects were evaluated using effective connectivity and beta oscillations coherence measures in areas connected to the treatment site as defined with cortico-cortical evoked potentials. Our results show that iTBS increases beta band synchronization within the sensorimotor network indicating a potential neuroplasticity effect. The effect is specific to the sensorimotor system, the beta frequency band and the stimulation pattern (no effect was found with single-pulse alpha stimulation). The effects outlasted the stimulation by three minutes. By characterizing the neurophysiological effects of iTBS within well-defined cortical networks, we hope to provide an electrophysiological framework that allows clinicians and researchers to optimize brain stimulation protocols which may have translational value.