Functional connectivity in self-limited epilepsy with centrotemporal spikes increases with epilepsy duration and interictal spike exposure

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Marie E Vasitas, Miguel S Menchaca, Beatrice S Goad, Xiwei She, Christopher Lee-Messer, Zihuai He, Fiona M Baumer

Epilepsia. 2026 Mar 30. doi: 10.1002/epi.70212. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine whether persistent exposure to interictal spikes is associated with progressive changes in functional connectivity in children with self-limited epilepsy with centrotemporal spikes (SeLECTS).

METHODS: Connectivity was calculated from electroencephalograms (EEGs) of 68 children with SeLECTS and 65 age- and sex-matched controls using the weighted phase lag index. First, we assessed whether connectivity increased with longer epilepsy duration, categorizing duration based on time since first seizure (less vs. greater than 6 months). Second, in a subset of 19 SeLECTS children with repeated EEGs, we assessed whether trajectory of connectivity over time differed based on persistence versus resolution of spikes. Connectivity during sleep and wakefulness was examined separately.

RESULTS: During sleep, connectivity was lowest in controls, intermediate in patients with recent onset epilepsy, and highest in those with longer epilepsy duration. Elevations in connectivity were greatest within the right occipital region at onset and became more widespread with longer epilepsy duration, especially increasing in the left temporal region. During wakefulness, connectivity in recent onset epilepsy trended lower than controls, whereas longer duration epilepsy trended higher, such that the two epilepsy groups differed significantly from each other but not from controls. In the cohort of children with repeated EEGs, patients with persistent spikes showed increasing connectivity over time in sleep, whereas those with spike resolution demonstrated decreasing connectivity over time. There were no significant changes in awake connectivity over time regardless of spike persistence or resolution.

SIGNIFICANCE: Functional connectivity in SeLECTS increases progressively with longer duration of spike exposure, suggesting that ongoing spikes drive neural network alterations. Spikes are a potential treatment target to prevent progressive brain network disruption and preserve cognitive outcomes.

PMID:41910930 | DOI:10.1002/epi.70212