Changes in neuronal firing and synchrony precede recruitment of mesial temporal networks into generalizing seizures

Amrit Misra

doi:10.17918/etd-4559

Despite extensive study, the mechanisms underlying seizure generation and propagation are poorly understood. One approach is to study changes in the neuronal activity (of inhibitory and excitatory subpopulations) that occur during the recruitment of networks into a propagating seizure, to gain insight into mechanisms by which seizures spread across the brain. Recent work, comparing intra- and extracelluar recordings in ex-vivo preparations of human neocortex has implicated a failure in feed-forward inhibition underlying the spread of seizure. However, direct in-vivo study of inhibitory and excitatory population dynamics in the neocortex is difficult, due to an inability to separate single neuron activity into excitatory and inhibitory subpopulations. In the mesial temporal lobe (MTL) it is considerably easier to isolate these subpopulations, and several studies in the rodent MTL have, indeed, demonstrated an intricate spatiotemporal interplay between inhibitory and excitatory neuron firing and their corresponding synchrony to local field potentials during the transition to seizure. While this work suggests potential mechanisms for network recruitment into seizure, no direct observations have been made in the MTL of epileptic patients. This report provides methods to prolong the longevity of single neuron recordings in the human MTL. Using these recordings, evidence is presented that supports the hypothesis that recruitment of MTL networks into seizures of neocortical origin is preceded by specific spatiotemporal increases in synchrony. In detail, within the MTL there is a decrease in inhibitory interneuron firing that coincides with the inhibitory population becoming more coherent to their local field potentials. This increased synchrony between neurons and the local field occurs at frequencies similar to those of regional synchrony between MTL networks and the seizure focus. These results suggest a mechanism by which downstream networks are prepared for recruitment into generalizing seizures. Interestingly, these spatiotemporal changes occur prior to the first electrographic manifestation of seizure in the brain, implying that in addition to their role in seizure propagation, changes in interneuron firing and interneuron-field synchrony in the MTL may be reflective of early seizure activity in other brain structures as well, and may thus be a useful tool in developing improved early detection algorithms.

Changes in neuronal firing and synchrony precede recruitment of mesial temporal networks into generalizing seizures

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Changes in neuronal firing and synchrony precede recruitment of mesial temporal networks into generalizing seizures

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