CLOSED-LOOP IMPLEMENTATION OF INTERSECTIONAL SHORT-PULSE (ISP) STIMULATION TO STOP TEMPORAL LOBE SEIZURES
01/30/2020
Tamás Földi1, 2, Gábor Kozák1, Anett J. Nagy1, Tamás Gyurkovics1, 2, Mihály Vöröslakos3, and Antal Berényi1, 2, 3
1 MTA-SZTE ‘Momentum’ Oscillatory Neuronal Networks Research Group, Department of Physiology, University of Szeged, Szeged H-6720, Hungary; 2Neunos Ltd, Szeged H-6720, Hungary; 3Neuroscience Institute, New York University, New York, New York 10016, USA
Transcutaneous electric stimulation (TES) using weak currents has been used extensively in attempts to influence brain activity. In vitro and in vivo experiments in rodents and computational modeling suggest that the magnitude of voltage gradient of the induced electric field should exceed 1 mV/mm to instantaneously and reproducibly alter neuronal spiking and consequent brain network patterns. Earlier, we determined the needed TES currents in human cadavers to achieve 1 mV/mm fields. We found that scalp stimulation greatly reduced the generated intracerebral electric fields and these measurements predicted that ~5 mA is needed to achieve 1mV/mm electric field gradient via scalp stimulation. To reach the desired intracerebral field strength without the adverse peripheral effects of >5 mA currents, we introduced a spatially focused multiple site, Intersectional Short-Pulse (ISP) stimulation. We demonstrated the instantaneous entraining effect of ISP on EEG waves in human subjects and on neuronal spiking in rats. Immediate effects of TES can be best utilized in disorders with sudden, major electrographic changes such as epileptic seizures. ISP also has the capacity to spatially focus its effect, thus it is capable to overcome the unwanted mirror effect (anodal vs cathodal) of the traditional TES protocols. We report here a novel stimulation pattern, that can simultaneously entrain both hippocampi. To evaluate its utility, temporal lobe seizures were induced in rats by electrical kindling, and each evoked seizure was automatically detected and silenced by a closed loop ISP stimulation. Lastly, we introduce our prototyping efforts to implement an implantable, minimal-invasive, transcranial closed-loop seizure termination device, aiming for human clinical applications.