The effect of topiramate on cognitive fMRI

Abstract

Purpose: Topiramate (TPM) is known to cause language impairment in healthy volunteers and patients with epilepsy. We assessed the effects of TPM on functional language networks in both patients with focal epilepsies and healthy controls using functional magnetic resonance imaging (fMRI).

Methods: We obtained fMRI data in 24 controls and 35 patients with frontal lobe epilepsy using a simple verbal fluency (VF) paradigm. Eight of the 35 patients were treated with TPM in polytherapy. We compared cognitive task related activations and de-activations in patients taking TPM with patients taking other AEDs and healthy controls. In a longitudinal pilot study with VF-fMRI paradigm, we studied two patients with focal epilepsies twice, prior to starting and on stable doses of TPM, two patients twice, before and after tapering TPM completely and two healthy controls twice, before and after single doses of 200mg TPM.

Key findings: Cross sectional analyses of VF-fMRI showed a reduction in the task-related deactivation of the default mode network (DMN) in patients taking TPM. The longitudinal study corroborated these findings as both chronic administration and a single dose of TPM were associated with impaired categorical verbal fluency and disruption of task-related deactivations.

Significance: Similar neuropsychological and fMRI findings in patients and healthy controls indicate a specific effect of TPM in default mode network areas that may be essential components of the language network. Our preliminary data suggest a mechanism by which TPM impairs cognitive processing during language function and highlights the sensitivity of fMRI to detect the effects of AEDs on cognitive brain networks.

Figure 1

FMRI results (cross-sectional analysis). Red maps represent activations and blue maps represent deactivations. (A and B) controls, (C and D) other FLE patients and (E and F) TPM patients. The reduced area of deactivation in TPM-group (F) suggests a specific effect of this AED on DMN activity. (G) and (H) are correlational analysis, showing the activation in precuneus correlated positively with increasing TPM dosage. (I) Correlation of fMRI activation for verbal fluency and TPM dosages at peak voxel in precuneus.

Figure 2

FMRI results (longitudinal pilot study). Red maps represent deactivations from TPM-on status and blue maps represent deactivations from TPM-off. The reduced deactivations in red suggest a specific effect of TPM in the DMN. (A–D) Patients; (E–F) healthy controls. (G) Results from the conjunction analysis, illustrating the common areas from 6 difference maps, including precuneus, bi-parietal and frontal areas.