Mechanisms underlying different onset patterns of focal seizures

Abstract

Focal seizures are episodes of pathological brain activity that appear to arise from a localised area of the brain. The onset patterns of focal seizure activity have been studied intensively, and they have largely been distinguished into two types—low amplitude fast oscillations (LAF), or high amplitude spikes (HAS). Here we explore whether these two patterns arise from fundamentally different mechanisms. Here, we use a previously established computational model of neocortical tissue, and validate it as an adequate model using clinical recordings of focal seizures. We then reproduce the two onset patterns in their most defining properties and investigate the possible mechanisms underlying the different focal seizure onset patterns in the model. We show that the two patterns are associated with different mechanisms at the spatial scale of a single ECoG electrode. The LAF onset is initiated by independent patches of localised activity, which slowly invade the surrounding tissue and coalesce over time. In contrast, the HAS onset is a global, systemic transition to a coexisting seizure state triggered by a local event. We find that such a global transition is enabled by an increase in the excitability of the “healthy” surrounding tissue, which by itself does not generate seizures, but can support seizure activity when incited. In our simulations, the difference in surrounding tissue excitability also offers a simple explanation of the clinically reported difference in surgical outcomes. Finally, we demonstrate in the model how changes in tissue excitability could be elucidated, in principle, using active stimulation. Taken together, our modelling results suggest that the excitability of the tissue surrounding the seizure core may play a determining role in the seizure onset pattern, as well as in the surgical outcome.

A theory of neocortical seizure spread: Insights from statistical physics

“…The waves produced by our model were similar to those of other models and to those observed in vivo [1, 3, 4, 6, 26, 28, 36, 38, 40, 61, 62], including plane waves, concentric waves emanating from a focus, secondary waves spawned from wave collision or from the patch boundary, annihilation of colliding waves, and spiral patterns. The gradual transition between clusters and waves may explain reports of microseizure activity fluctuating between clusters and ‘expanding and contracting’ waves with variable degrees of organization [18].…”

“…In order to understand these relationships, some have hypothesized that microseizures form ‘small clusters of pathologically connected neurons’, which coalesce to produce macroscopic, clinical seizures [22–26]. There is also evidence that the transition from microscopic dynamics to macroscopic waves occurs when a small ‘ictal core’ of wave activity strongly inhibits a surrounding area of sparsely distributed active neurons, and that EEG waves are associated with this inhibition [11, 27].…”

“…It has been difficult, however, to find a model that is both intuitive and capable of capturing more than a few of the key features of seizure behavior. Some models lack spatial relationships [34], some require interactions between every pair of cortical columns [35], and some lack clusters or spirals, or require many differential equations and many assumptions of parameter values [5, 6, 26, 36–40]. Other models address large-scale connectivity but depend on variables without obvious intuitive biological meaning [31, 41, 42].…”

A theoretical model for focal seizure initiation, propagation, termination, and progression

“…These outward traveling waves result in the EEG appearance of rhythmic discharging at seizure onset. Previous studies have proposed that this "hypersynchronous" seizure onset pattern depends on long-range cortical connections (Perucca et al, 2014;Weiss et al, 2016), or increased surrounding tissue excitability (Wang et al, 2017).…”

Capturing remote activation of epilepsy source?

“…When comparing these findings with our results, we imply that activating of a source of epilepsy mainly occurs through horizontal, 'intra-layer' connections of the cerebral cortex. Note that previous mechanistic neuronal-network models of focal epilepsy [109,110] (as well as the phenomenological neural mass/field models, e.g., [111][112][113][114][115][116][117][118][119]) do not explicitly address the remote activation. At last, it is also worth mentioning that the modeling results confirm the assumption made in seizure prediction method [120] about the involvement of distant neurons in activating the SOZ.…”