Rebound Excitation of Epileptic Brain Activities After Transcranial Focused Ultrasound Stimulation

Transcranial focused ultrasound stimulation has recently shown its feasibility in inducing anticonvulsant effects. However, its association with rebound excitation is yet unknown although adverse effects caused by post-inhibitory rebound excitations have been reported for conventional antiepileptic therapies. In this study, rebound excitations with transcranial focused ultrasound were firstly demonstrated, and the modulation of epileptiform activities towards both suppressive and excitatory responses were investigated following ultrasound stimulations. For the experiment, ultrasound was applied on the thalamus of a chemically induced acute epilepsy rat model. Sonication effects were monitored via electroencephalography (n=38), immunohistochemical analysis (n=24), and optical measurement of cerebral blood volume changes (n=18). While ultrasonic stimuli patterns with long intervals showed antiepileptic effects on electroencephalography, those with short intervals showed rebound excitatory responses followed by inhibitory activities. Additionally, suppressive states induced by inhibitory stimulations were transformed into excitatory states by consecutively applying short acoustic bursts with higher pressure. Cerebral blood volume changes demonstrated consistent results with the electroencephalography. Immunohistochemistry revealed that both inhibitory and excitatory neuronal cells were activated to generate rebound excitatory conditions, while inhibitory cells were activated for suppressive conditions. Our first discovery of the rebound excitations would provide safety guidelines in epilepsy patients with ultrasound stimulation.