Atypical language lateralisation associated with right fronto-temporal grey matter increases — a combined fMRI and VBM study in left-sided mesial temporal lobe epilepsy patients

Abstract

By combining language functional magnetic resonance imaging and voxel-based morphometry in patients with left-sided mesial temporal lobe epilepsy and hippocampal sclerosis, we studied whether atypical language dominance is associated with temporal and/or extratemporal cortical changes. Using verbal fluency functional magnetic resonance imaging for language lateralisation, we identified 20 patients with left-sided mesial temporal lobe epilepsy with hippocampal sclerosis and atypical language lateralisation. These patients were compared with a group of 20 matched left-sided mesial temporal lobe epilepsy patients who had typical language lateralisation. Using T1-weighted 3D images of all patients and voxel-based morphometry, we compared grey matter volumes between the groups of patients. We also correlated grey matter volumes with the degree of atypical language activation. Patients with atypical language lateralisation had increases of grey matter volumes, mainly within right-sided temporo-lateral cortex (x = 59, y = − 16, z = − 1, T = 6.36, p < .001 corrected), and less significantly within frontal brain regions compared to patients with typical language lateralisation. The degree of atypical fronto-temporal language activation (measured by lateralisation indices and relative functional magnetic resonance imaging activity) was correlated with right-sided temporal and frontal grey matter volumes. Patients with atypical language lateralisation did not differ in terms of language performance from patients with typical language dominance. Atypical language lateralisation in patients with left-sided mesial temporal lobe epilepsy was associated with increased grey matter volume within the non-epileptic right temporal and frontal lobe. Grey matter increases associated with atypical language might represent morphological changes underlying functional reorganisation of the language network. This hard-wired reorganised atypical language network seems to be suitable to support language functions.

Introduction

Language lateralisation in patients with epilepsy differs from what is known in the normal population (Springer et al., 1999). Atypical, i.e. bilateral or right-sided representations of language are more frequent in patients with epilepsy and seemed to be associated with left-sided seizure origin, an early age of onset, left handedness, and a lesion in the vicinity of primary language areas of Broca and Wernicke (Woermann et al., 2003). Even the presence of an epileptogenic lesion remote from primary language areas, like hippocampal sclerosis (HS) has an impact on language dominance. Mesial temporal lobe epilepsy (TLE) patients with HS are more likely to have atypical language organisation compared to TLE patients without HS (Janszky et al., 2003, Maccotta et al., 2007, Richardson et al., 2003, Weber et al., 2006). In TLE patients with HS, interictal epileptic activity propagating to the ipsilateral neocortex and measured by surface EEG, has been associated with atypical language dominance. In those patients, higher frequencies of left-sided spikes representing a more widespread epileptic network were linked to a shift of language representation from left to right (Janszky et al., 2003, Janszky et al., 2006). A direct role of the diseased hippocampus within reorganising language networks of TLE patients has been proposed by Liégeois et al. (2004) and is also discussed by Weber et al. (2006).

Studies investigating the morphological correlates of atypical language representation in epilepsy patients are rare. In a study of GM volume changes in epilepsy patients, Foundas et al. (1996) reported a rightward asymmetry of the pars triangularis of the frontal operculum in a single TLE patient with right-sided language lateralisation. Manually measuring the volume of the planum temporale, Oh and Koh (2009) showed a rightward volume asymmetry in 7/10 patients with atypical language representation. In contrast, Dorsaint-Pierre et al. (2006) found leftward asymmetries in the planum temporale and in Heschl's gyri in patients with poorly characterised epilepsy independent of language lateralisation. It remained unclear whether atypical language lateralisation and associated morphological brain changes are a phenomenon of left-sided TLE.

In the current study, we addressed the question whether in patients with left-sided TLE and HS atypical language dominance is associated with hippocampal and extrahippocampal changes in grey matter (GM) volume measured using voxel-based morphometry (VBM). We hypothesised volume changes within language-associated regions such as the inferior frontal gyrus and the lateral temporal lobe. In patients with atypical language organisation, we hypothesised fronto-temporo-lateral decreases of GM in the left hemisphere and volume increases within in the right hemisphere. Based on the results of Liégeois et al., 2004, Weber et al., 2006, we also hypothesised that patients with left-sided TLE and atypical language dominance had more GM volumes within the right hippocampus compared to patients with typical language representation.