What Triggers the Interictal Epileptic Spike? A Multimodal Multiscale Analysis of the Dynamic of Synaptic and Non-synaptic Neuronal and Vascular Compartments Using Electrical and Optical Measurements

Interictal spikes (IISs) may result from a disturbance of the intimate functional balance between various neuronal (synaptic and non-synaptic), vascular, and metabolic compartments. To better characterize the complex interactions within these compartments at different scales we developed a simultaneous multimodal-multiscale approach and measure their activity around the time of the IIS. We performed such measurements in an epileptic rat model (n = 43). We thus evaluated (1) synaptic dynamics by combining electrocorticography and multiunit activity recording in the time and time-frequency domain, (2) non-synaptic dynamics by recording modifications in light scattering induced by changes in the membrane configuration related to cell activity using the fast optical signal, and (3) vascular dynamics using functional near-infrared spectroscopy and, independently but simultaneously to the electrocorticography, the changes in cerebral blood flow using diffuse correlation spectroscopy. The first observed alterations in the measured signals occurred in the hemodynamic compartments a few seconds before the peak of the IIS. These hemodynamic changes were followed by changes in coherence and then synchronization between the deep and superficial neural networks in the 1 s preceding the IIS peaks. Finally, changes in light scattering before the epileptic spikes suggest a change in membrane configuration before the IIS. Our multimodal, multiscale approach highlights the complexity of (1) interactions between the various neuronal, vascular, and extracellular compartments, (2) neural interactions between various layers, (3) the synaptic mechanisms (coherence and synchronization), and (4) non-synaptic mechanisms that take place in the neuronal network around the time of the IISs in a very specific cerebral hemodynamic environment.