Role of Language-Related Functional Connectivity in Patients with Benign Childhood Epilepsy with Centrotemporal Spikes

Abstract

Background and purpose: Benign childhood epilepsy with centrotemporal spikes (BECTS) does not always have a benign cognitive outcome. We investigated the relationship between cognitive performance and altered functional connectivity (FC) in the resting-state brain networks of BECTS patients.

Methods: We studied 42 subjects, comprising 19 BECTS patients and 23 healthy controls. Cognitive performance was assessed using the Korean version of the Wechsler Intelligence Scale for Children-III, in addition to verbal and visuospatial memory tests and executive function tests. Resting-state functional magnetic resonance imaging was acquired in addition to high-resolution structural data. We selected Rolandic and language-related areas as regions of interest (ROIs) and analyzed the seed-based FC to voxels throughout the brain. We evaluated the correlations between the neuropsychological test scores and seed-based FC values using the same ROIs.

Results: The verbal intelligence quotient (VIQ) and full-scale intelligence quotient (FSIQ) were lower in BECTS patients than in healthy controls (p<0.001). The prevalence of subjects with a higher performance IQ than VIQ was significantly higher in BECTS patients than in healthy controls (73.7% vs. 26.1%, respectively; p=0.002). Both the Rolandic and language-related ROIs exhibited more enhanced FC to voxels in the left inferior temporal gyrus in BECTS patients than in healthy controls. A particularly interestingly finding was that the enhanced FC was correlated with lower cognitive performance as measured by the VIQ and the FSIQ in both patients and control subjects.

Conclusions: Our findings suggest that the FC alterations in resting-state brain networks related to the seizure onset zone and language processing areas could be related to adaptive plasticity for coping with cognitive dysfunction.

Keywords: benign childhood epilepsy with centrotemporal spikes; cognition; functional connectivity; functional magnetic resonance imaging; intelligence quotient.

Fig. 1. Group differences in the cognitive performance between BECTS patients and control subjects. A: The control group showed a higher proportion of subjects with a VIQ>PIQ discrepancy, whereas the patient group contained a significantly higher percentage of those with a PIQ>VIQ discrepancy (p=0.002). B: The eight frequent (>1 per minute) ED presenters in the patient group exhibited a lower VCI than the infrequent ED presenters (p=0.064). BECTS: benign childhood epilepsy with centrotemporal spikes, ED: epileptiform discharge, PIQ: performance intelligence quotient, VCI: verbal comprehension index, VIQ: verbal intelligence quotient.

Fig. 2. Group differences in the seed-based FC patterns between BECTS patients and control subjects. A: Increased FC was observed with voxels in the left inferior temporal gyrus in the patient group than in the control group when using a Rolandic mask covering the bilateral inferior frontal gyri (pars triangularis and pars opercularis) and the Rolandic operculum and insula as the seed. B: Increased FC was observed with voxels in the left inferior temporal gyrus in the patient group than in the control group when using a language mask covering the bilateral inferior frontal gyri, middle and superior temporal gyri, and supramarginal gyri in addition to the left angular gyrus and left cerebellar crus I as the seed. BECTS: benign childhood epilepsy with centrotemporal spikes, FC: functional connectivity.

Fig. 3. Relationship between intelligence quotient scores on the Korean version of the Wechsler Intelligence Scale for Children-III and Rolandic FC. Rolandic FC to voxels in the left inferior temporal gyrus, which was greater in the patient group (red dots) than the control group (blue squares), was correlated with greater impairment of cognitive performance as measured by (A) VIQ (r=−0.501, p=0.0007), (B) PIO (r=−0.330, p=0.0329), and (C) FSIQ (r=−0.472, p=0.0016). The cutoff for statistical significance was a corrected p of 0.0071. FC: functional connectivity, FSIQ: full-scale intelligence quotient, PIQ: performance intelligence quotient, VIQ: verbal intelligence quotient.

Fig. 4. Relationship between Korean version of the Wechsler Intelligence Scale for Children-III intelligence quotient scores and language FC. Language FC to voxels in the left inferior temporal gyrus, which was greater in the patient group (red dots) than in the control group (blue squares), was correlated with greater impairment of cognitive performance as measured by (A) VIQ (r=−0.541, p=0.0002), (B) PIQ (r=−0.400, p=0.0086), and (C) FSIQ (r=−0.526, p=0.0003). The cutoff for statistical significance was a corrected p of 0.0071. FC: functional connectivity, FSIQ: full-scale intelligence quotient, PIQ: performance intelligence quotient, VIQ: verbal intelligence quotient.