Connectomic Profiles and Cognitive Trajectories After Epilepsy Surgery in Children.

BACKGROUND AND OBJECTIVES: Neurocognitive outcomes after surgery for temporal lobe epilepsy in childhood are variable. Postoperative changes are not directly predicted by seizure freedom, and associations between epilepsy, neuropsychological function, and developing neural networks are poorly understood. Here, we leveraged whole-brain connectomic profiling in magnetoencephalography (MEG) to retrospectively study associations between brain connectivity and neuropsychological function in children with temporal lobe epilepsy undergoing resective surgery. METHODS: Clinical and MEG data were retrospectively analyzed for children who underwent temporal lobe epilepsy surgery at the Hospital for Sick Children from 2000 to 2021. Resting-state connectomes were constructed from neuromagnetic oscillations via the weighted-phase lag index. Using a partial least-squares (PLS) approach, we assessed multidimensional associations between patient connectomes, neuropsychological scores, and clinical covariates. Bootstrap resampling statistics were performed to assess statistical significance. RESULTS: A total of 133 medical records were reviewed, and 5 PLS analyses were performed. Each PLS analysis probed a particular neuropsychological domain and the associations between its baseline and postoperative scores and the connectomic data. In each PLS analysis, a significant latent variable was identified, representing a specific percentage of the variance in the data and relating neural networks to clinical covariates, which included changes in rote verbal memory (n = 41, p = 0.01, σ2 = 0.38), narrative/verbal memory (n = 57, p = 0.00, σ2 = 0.52), visual memory (n = 51, p = 0.00, σ2 = 0.43), working memory (n = 44, p = 0.00, σ2 = 0.52), and overall intellectual function (n = 59, p = 0.00, σ2 = 0.55). Children with more diffuse, bilateral intrinsic connectivity across several frequency bands showed lower scores on all neuropsychological assessments but demonstrated a greater propensity for gains after resective surgery. DISCUSSION: Here, we report that connectomes characterized by diffuse connectivity, reminiscent of developmentally immature networks, are associated with lower preoperative cognition and postoperative cognitive improvement. These findings provide a potential means to understand neurocognitive function in children with temporal lobe epilepsy and expected changes postoperatively.

Spectral changes following resective epilepsy surgery and neurocognitive function in children with epilepsy.

Decelerated resting cortical oscillations, high-frequency activity, and enhanced cross-frequency interactions are features of focal epilepsy. The association between electrophysiological signal properties and neurocognitive function, particularly following resective surgery, is, however, unclear. In the current report, we studied intraoperative recordings from intracranial electrodes implanted in seven children with focal epilepsy and analyzed the spectral dynamics both before and after surgical resection of the hypothesized seizure focus. The associations between electrophysiological spectral signatures and each child's neurocognitive profiles were characterized using a partial least squares analysis. We find that extent of spectral alteration at the periphery of surgical resection, as indexed by slowed resting frequency and its acceleration following surgery, is associated with baseline cognitive deficits in children. The current report provides evidence supporting the relationship between altered spectral properties in focal epilepsy and neuropsychological deficits in children. In particular, these findings suggest a critical role of disrupted thalamocortical rhythms, which are believed to underlie the spectral alterations we describe, in both epileptogenicity and neurocognitive function.NEW & NOTEWORTHY Spectral alterations marked by decelerated resting oscillations and ectopic high-frequency activity have been noted in focal epilepsy. We leveraged intraoperative recordings from chronically implanted electrodes pre- and postresection to understand the association between these electrophysiological phenomena and neuropsychological function. We find that the extent of spectral alteration, indexed by slowed resting frequency and its acceleration following resection, is associated with baseline cognitive deficits. These findings provide novel insights into neurocognitive impairments in focal epilepsy.

Temporal-plus epilepsy in children: A connectomic analysis in magnetoencephalography.

OBJECTIVE: Seizure recurrence following surgery for temporal lobe (TL) epilepsy may be related to extratemporal epileptogenic foci, so-called temporal-plus (TL+) epilepsy. Here, we sought to leverage whole brain connectomic profiling in magnetoencephalography (MEG) to identify neural networks indicative of TL+ epilepsy in children. METHODS: Clinical and MEG data were analyzed for 121 children with TL and TL+ epilepsy spanning 20 years at the Hospital for Sick Children. Resting-state connectomes were derived using the weighted phase lag index from neuromagnetic oscillations. Multidimensional associations between patient connectomes, TL versus TL+ epilepsy, seizure freedom, and clinical covariates were performed using a partial least squares (PLS) analysis. Bootstrap resampling statistics were performed to assess statistical significance. RESULTS: A single significant latent variable representing 66% of the variance in the data was identified with significant contributions from extent of epilepsy (TL vs TL+), duration of illness, and underlying etiology. This component was associated with significant bitemporal and frontotemporal connectivity in the theta, alpha, and beta bands. By extracting a brain score, representative of the observed connectivity profile, patients with TL epilepsy were dissociated from those with TL+, independent of their postoperative seizure outcome. SIGNIFICANCE: By analyzing 121 connectomes derived from MEG data using a PLS approach, we find that connectomic profiling could dissociate TL from TL+ epilepsy. These findings may inform patient selection for resective procedures and guide decisions surrounding invasive monitoring.

Thalamocortical dysrhythmia in intraoperative recordings of focal epilepsy.

Resonant interactions between the thalamus and cortex subserve a critical role for maintenance of consciousness as well as cognitive functions. In states of abnormal thalamic inhibition, thalamocortical dysrhythmia (TCD) has been described. The characteristics of TCD include a slowing of resting oscillations, ectopic high-frequency activity, and increased cross-frequency coupling. Here, we demonstrate the presence of TCD in four patients who underwent resective epilepsy surgery with chronically implanted electrodes under anesthesia, continuously recording activity from brain regions at the periphery of the epileptogenic zone before and after resection. Following resection, we report an acceleration of the large-scale network resting frequency coincident with decreases in cross-frequency phase-amplitude coupling. Interregional functional connectivity in the surrounding cortex was also increased following resection of the epileptogenic focus. These findings provide evidence for the presence of TCD in focal epilepsy and highlight the importance of reciprocal thalamocortical oscillatory interactions in defining novel biomarkers for resective surgeries. NEW & NOTEWORTHY Thalamocortical dysrhythmia (TCD) occurs in the context of thalamic dysfacilitation and is characterized by slowing of resting oscillations, ectopic high-frequency activity, and cross-frequency coupling. We provide evidence for TCD in focal epilepsy by studying electrophysiological changes occurring at the periphery of the resection margin. We report acceleration of resting activity coincident with decreased cross-frequency coupling and increased functional connectivity. The study of TCD in epilepsy has implications as a biomarker and therapeutic target.