Speaker
Description
The application of centromedian stimulation (CMS) has been limited by the lack of clarity regarding its mode of action. In this study, we used stereoelectroencephalography (SEEG) signals from a patient with focal cortical dysplasia. The suppression of neocortical interictal activity with CMS was frequency-dependent: no effect at 50 Hz, 15s suppression at 100Hz and ~2s suppression at 70 and 150 Hz. We developed a neurophysiologically-plausible thalamocortical model to simulate the recorded thalamic and neocortical SEEGs. The sustained suppression of interictal activity in the neocortex was modelled by incorporating extrasynaptic-inhibition and short-term plasticity mechanisms in the thalamic compartment. The model is based on two assumptions. First, high-frequency CMS strongly activates the inhibitory subpopulations in the thalamus. This causes GABA-spillover that engages postsynaptic and extrasynaptic GABAergic-receptors of the thalamic cells. Their engagement decreases thalamic glutamatergic input to the neocortical pyramidal cells, and subsequently suppresses interictal discharges. Second, during 150Hz CMS, we hypothesize that the activation of presynaptic GABA-B-receptors and an increased rate of GABA reuptake facilitate the reappearance of neocortical interictal activity. The effect of each of the mechanisms implemented was quantified by rigorously comparing simulated and the recorded SEEG signals in terms of their signal morphology and interictal spiking frequency.
