Neuroimaging correlates of language network impairment and reorganization in temporal lobe epilepsy

Abstract

Advanced, noninvasive imaging has revolutionized our understanding of language networks in the brain and is reshaping our approach to the presurgical evaluation of patients with epilepsy. Functional magnetic resonance imaging (fMRI) has had the greatest impact, unveiling the complexity of language organization and reorganization in patients with epilepsy both pre- and postoperatively, while volumetric MRI and diffusion tensor imaging have led to a greater appreciation of structural and microstructural correlates of language dysfunction in different epilepsy syndromes. In this article, we review recent literature describing how unimodal and multimodal imaging has advanced our knowledge of language networks and their plasticity in epilepsy, with a focus on the most frequently studied epilepsy syndrome in adults, temporal lobe epilepsy (TLE). We also describe how new analytic techniques (i.e., graph theory) are leading to a refined characterization of abnormal brain connectivity, and how subject-specific imaging profiles combined with clinical data may enhance the prediction of both seizure and language outcomes following surgical interventions.

Figure 1

Hierarchy of 15 typical and atypical language patterns based on categorical criteria in both patients and controls. Language is classified into 3 levels: typical=atypical, language dominance (left, bilateral, crossed, or right), and individual activation patterns. Regions of interest are left lateralized if lateralization index (LI) ≥ 0.20, bilateral if LI < |0.20|, and right lateralized if LI ≤ −20.20. IFG = inferior frontal gyrus; WA = Wernicke area. Figure modified with author's permission.

Figure 2

Connectivity maps of controls and patients with left temporal lobe epilepsy (TLE) for four seed regions. (A) Brain activity during the language production in a group of 30 healthy controls. Results are overlaid onto the mean echo planar imaging of the 30 subjects (activation in red-yellow, deactivation in blue-white). Group analysis is performed using a mixed effects model and thresholded at p value less than 0.05, corrected for multiple comparisons. The approximate locations of the four seed regions are shown as colored rings: anterior cingulate cortex (ACC) (red), posterior cingulate cortex (PCC) (blue), left IFG (green), and left middle frontal gyrus (MFG) (yellow). (B–E) The results of performing functional connectivity analysis on a separate cohort of 8 healthy controls (left panels), together with a group of 17 patients with left TLE (right panels). Regions functionally connected (correlated) with the ROI average signal time course in the left IFG (B), PCC (C), left MFG (D) and ACC (E).

Figure 3

Schematic depiction of the rsFC relations associated with stronger left hemispheric specialization for language, shown in separate panels for the left- (A) and right- (B) sided seeds. Note, weaker hemispheric specialization (weaker laterality) is associated with the inverse rsFC patterns emerging from the seeds. Importantly, both our left and right TLE patients displayed these general patterns. Blue lines represent reduced rsFC with stronger specialization. Red lines represent higher rsFC with stronger specialization.

Figure 4

DTI fiber tracts implicated in language processing generated from a probabilistic fiber track atlas. ARC, arcuate fasciculus; ILF, inferior longitudinal fasciculus; UNC, uncinate fasciculus; IFOF, inferior fronto-occipital fasciculus.