Reduced functional integration of the sensorimotor and language network in rolandic epilepsy

Abstract

Introduction: Over the last years, evidence has accumulated that rolandic epilepsy (RE) is associated with serious cognitive comorbidities, including language impairment. However, the cerebral mechanism through which epileptiform activity in the rolandic (sensorimotor) areas may affect the language system is unknown. To investigate this, the connectivity between rolandic areas and regions involved in language processing is studied using functional MRI (fMRI).

Materials and methods: fMRI data was acquired from 22 children with rolandic epilepsy and 22 age-matched controls (age range: 8-14 years), both at rest and using word-generation and reading tasks. Activation map analysis revealed no group differences (FWE-corrected, p < 0.05) and was therefore used to define regions of interest for pooled (patients and controls combined) language activation. Independent component analysis with dual regression was used to identify the sensorimotor resting-state network in all subjects. The associated functional connectivity maps were compared between groups at the regions of interest for language activation identified from the task data. In addition, neuropsychological language testing (Clinical Evaluation of Language Fundamentals, 4th edition) was performed.

Results: Functional connectivity with the sensorimotor network was reduced in patients compared to controls (p = 0.011) in the left inferior frontal gyrus, i.e. Broca's area as identified by the word-generation task. No aberrant functional connectivity values were found in the other regions of interest, nor were any associations found between functional connectivity and language performance. Neuropsychological testing confirmed language impairment in patients relative to controls (reductions in core language score, p = 0.03; language content index, p = 0.01; receptive language index, p = 0.005).

Conclusion: Reduced functional connectivity was demonstrated between the sensorimotor network and the left inferior frontal gyrus (Broca's area) in children with RE, which might link epileptiform activity/seizures originating from the sensorimotor cortex to language impairment, and is in line with the identified neuropsychological profile of anterior language dysfunction.

Keywords: ICA, independent component analysis; Independent component analysis; Language impairment; RE, rolandic epilepsy; Resting-state fMRI; Resting-state networks; Rolandic epilepsy; Sensorimotor/rolandic network.

Graphical abstract

Fig. 1

Region of interest rolandic network connectivity. The left inferior frontal gyrus is selected as a region of interest from the pooled word-generation activation map (left) and used to extract subject-specific values from the rolandic connectivity maps (right), which represent the degree of similarity between the voxel time series and the rolandic independent component (weight of the rolandic independent component in a full independent component fit to the data). Color bars represent pooled activation level (t-contrast, corrected for family-wise error (FWE) at p < 0.05) and rolandic connectivity for a representative subject, respectively. Images are normalized to MNI-space.

Fig. 2

Activation maps. Pooled activation maps (i.e. patients and controls combined) for A: word-generation and B: reading. In word-generation, the anterior cingulate cortex (A1), left inferior prefrontal cortex (A2) and bilateral insular regions (A3) were activated. Reading induced activity in posterior (B1–2) and anterior (B3) bilateral mid temporal regions. Z-values indicate MNI slice coordinates, the colorbar gives the activation t-statistic and activation maps are given for p < 0.05 (family-wise error (FWE) corrected). Regions of interest are overlaid in transparent white, the one in the right inferior prefrontal cortex (A2) was constructed by mirroring with respect to the median plane. Z-values indicate axial MNI coordinates.

Fig. 3

Rolandic resting-state network as identified using pooled group independent component analysis. This involves the bilateral sensorimotor areas (pre- and postcentral gyrus), superior temporal, cerebellar, and medial regions. Note the involvement of a left inferior prefrontal region (arrowheads), which is absent at the right. Colorbar: voxel-wise F-value for the test on the relevance of the rolandic independent component (IC) to the full-IC fit of the pooled data concatenated over time. Results are normalized to MNI-space.

Fig. 4

Local reduction of rolandic network connectivity. The rolandic network of A) controls and B) patients (blue). Rolandic network functional connectivity is reduced in patients compared to controls (red colorbar; identical overlay in A and B) outside (but directly adjacent to) the network itself. This local reduction of connectivity coincides with a region of activation for word-generation (white circle; p = 0.011). See text for details. Maps generated by permutation testing (N = 5000, p < 0.05); rolandic network cluster corrected. Colorbar: p-value for the group difference. Results are normalized to MNI-space.