Single-cell Networks Reorganise to Facilitate Whole-brain Supercritical Dynamics During Epileptic Seizures

Abstract

Excitation-inhibition (EI) balance may be required for the organisation of brain dynamics to a phase transition, criticality, which confers computational benefits. Brain pathology associated with EI imbalance may therefore occur due to a deviation from criticality. However, evidence linking critical dynamics with EI imbalance-induced pathology is lacking. Here, we studied the effect of EI imbalance-induced epileptic seizures on brain dynamics, using in vivo whole-brain 2-photon imaging of GCaMP6s larval zebrafish at single-neuron resolution. We demonstrate the importance of EI balance for criticality, with EI imbalance causing a loss of whole-brain critical statistics. Using network models we show that a reorganisation of network topology drives this loss of criticality. Seizure dynamics match theoretical predictions for networks driven away from a phase transition into disorder, with the emergence of chaos and a loss of network-mediated separation, dynamic range and metastability. These results demonstrate that EI imbalance drives a pathological deviation from criticality.

Altered spreading of neuronal avalanches in temporal lobe epilepsy relates to cognitive performance: A resting‐state hdEEG study

“…It might be that a potential alteration of the regional excitation/inhibition (E/I) balance could facilitate the recruitment of a given brain region by the ongoing transient large‐scale perturbations. In the same line of thinking, Burrows et al 50 observed that manipulating the E/I balance in cellular, in vivo neural networks caused a shift of the operational regimen away from criticality, which was linked, in turn, to the emergence of epileptic activity. Beyond the neuroscientific implications, our methodology might directly help the patients' management.…”

Altered spreading of neuronal avalanches in temporal lobe epilepsy relates to cognitive performance: a resting-state hdEEG study

“…It might be that a potential alteration of the regional excitation/inhibition (E/I) balance could facilitate the recruitment of a given brain region by the ongoing transient large-scale perturbations. In the same line of thinking, Burrows and colleagues (Burrows et al, 2021) observed that manipulating the E/I balance in cellular in vivo neural networks caused a shift of the operational regime away from criticality which was linked, in turn, to the emergence of epileptic activity. Beyond the neuroscientific implications, our methodology might directly help the patients’ management.…”

Whole-brain imaging of freely-moving zebrafish

“…However a significant limitation of point-scanning 2-photon microscopy is speed, since it scans the tissue 1 voxel at a time. With recent implementation of resonant scanning mirrors, imaging speeds have been achieved of 1–1.2 Hz for 9 to 12 planes over 76 μm (Andalman et al, 2019 ), 2.7 Hz for 10 planes over 150 μm (Burrows et al, 2021 ), and 9.7 Hz for 5 planes of just the tectum (Sainsbury et al, 2023 ). In 2-photon light-sheet microscopy the light sheet consists of 2-photon excitation generated by scanning a pulsed infrared laser source (Truong et al, 2011 ; Wolf et al, 2015 ).…”