Neural Gain Amplification and mode-mixing lead to cortico-hippocampal state-transitions

Cortico-hippocampal interactions are fundamental to cognitive processes as well as neurological disorders, yet the mechanisms underlying their coordinated dynamics remain poorly understood. Here, we address this knowledge gap by modelling the cortex and the hippocampus as interconnected neural sheets, incorporating their geometric, physiological, and connectivity profiles. Cortico-thalamic and hippocampal-thalamic systems, considered in isolation, show dynamics characteristic of canonical brain rhythms including alpha, beta, and theta rhythms. Integrating the cortico-hippocampal system is achieved by implementing topologically informed cortico-hippocampal coupling. We first show that this coupling pushes the system as a whole toward a critical state, triggering state transitions that do not arise in the two isolated systems. Coupling between the cortex and the hippocampus also leads to mode mixing, facilitating the transfer of frequencies between these two systems. Such mode-mixing, along with gain amplification can destabilize the neural activity, providing an explanation for the frequent involvement of the hippocampus in seizure activity. This prediction is validated using intracranial electroencephalographic data from human patients with epilepsy. This modelling framework offers key insights into cortico-hippocampal dynamics and lays the groundwork for understanding other cortical-subcortical interactions.