Topiramate and its effect on fMRI of language in patients with right or left temporal lobe epilepsy

Abstract

Topiramate (TPM) is well recognized for its negative effects on cognition, language performance and lateralization results on the intracarotid amobarbital procedure (IAP). But, the effects of TPM on functional MRI (fMRI) of language and the fMRI signals are less clear. Functional MRI is increasingly used for presurgical evaluation of epilepsy patients in place of IAP for language lateralization. Thus, the goal of this study was to assess the effects of TPM on fMRI signals. In this study, we included 8 patients with right temporal lobe epilepsy (RTLE) and 8 with left temporal lobe epilepsy (LTLE) taking TPM (+TPM). Matched to them for age, handedness and side of seizure onset were 8 patients with RTLE and 8 with LTLE not taking TPM (-TPM). Matched for age and handedness to the patients with TLE were 32 healthy controls. The fMRI paradigm involved semantic decision/tone decision task (in-scanner behavioral data were collected). All epilepsy patients received a standard neuropsychological language battery. One sample t-tests were performed within each group to assess task-specific activations. Functional MRI data random-effects analysis was performed to determine significant group activation differences and to assess the effect of TPM dose on task activation. Direct group comparisons of fMRI, language and demographic data between patients with R/L TLE +TPM vs. -TPM and the analysis of the effects of TPM on blood oxygenation level-dependent (BOLD) signal were performed. Groups were matched for age, handedness and, within the R/L TLE groups, for the age of epilepsy onset/duration and the number of AEDs/TPM dose. The in-scanner language performance of patients was worse when compared to healthy controls - all p<0.044. While all groups showed fMRI activation typical for this task, regression analyses comparing L/R TLE +TPM vs. -TPM showed significant fMRI signal differences between groups (increases in left cingulate gyrus and decreases in left superior temporal gyrus in the patients with LTLE +TPM; increases in the right BA 10 and left visual cortex and decreases in the left BA 47 in +TPM RTLE). Further, TPM dose showed positive relationship with activation in the basal ganglia and negative associations with activation in anterior cingulate and posterior visual cortex. Thus, TPM appears to have a different effect on fMRI language distribution in patients with R/L TLE and a dose-dependent effect on fMRI signals. These findings may, in part, explain the negative effects of TPM on cognition and language performance and support the notion that TPM may affect the results of language fMRI lateralization/localization.

Fig. 1

Statistical maps for the SDTD task in (a) healthy subjects and (b) epilepsy subjects. Warm colors in (a) and (b) represent activation greater for semantic than tone decisions, while cool colors represent greater activation for tone than for semantic decisions. Regression analyses were also performed to directly compare patients with (c) LTLE and (d) RTLE who were treated (+TPM) and not treated (−TPM) with TPM and (e) the effect of TPM dose on task activation in +TPM patients. Warm colors in (c) and (d) represent overall increased activation in TPM-treated patients compared to untreated patients (+TPM > −TPM), while cool colors represent greater activation for untreated relative to TPM-treated patients (+TPM < −TPM). In (e), warm colors represent a positive association and cool colors represent a negative association between TPM dose and activation during the SDTD task. Correlation analyses revealed a positive relationship between performance on semantic decision making and activation in the left cingulate gyrus of patients with LTLE (c1), while negative associations were found between RTLE performance on the BNT and activation in the right superior frontal gyrus (d1) and the left visual association cortex (d2). On the scatterplots, data points in orange are +TPM subjects and in blue are −TPM subjects. Activated regions in statistical maps are significant at p<0.05 corrected for multiple voxel comparisons, with a cluster size of at least 60 contiguous voxels. Each statistical map is presented in radiological convention with left in the image as right in the brain and superimposed on an average T₁-weighted image generated from all healthy subjects (a) or subjects with TLE (b–e). The 12 axial slices selected for each display panel range in Talairach coordinates from Z = −17 mm (top left) to Z = +27 mm (bottom right).