Left-sided interictal epileptic activity induces shift of language lateralization in temporal lobe epilepsy:: An fMRI study

Purpose: By using speech-activated functional MRI (fMRI), we investigated whether the frequency of left-sided interictal epileptic activity (IED: spikes or sharp waves on the EEG) is associated with atypical speech lateralization. Methods: We investigated 28 patients (13 men, aged 17-59 years) with left-sided mesial temporal lobe epilepsy (MTLE) and 11 patients with right-sided MTLE as a control population. Only patients with unilateral hippocampal sclerosis with unilateral IED were included. For fMRI of individual patients, we contrasted images sampled during covert word generation with a low-level rest condition. With SPM99, an individual comparison for the contrast word generation versus resting inactivity was conducted. To characterize speech lateralization in individual patients, we calculated asymmetry indexes (AIs): the difference between activated left-sided and right-sided voxels was divided by all activated voxels. Analyzing long-term EEG, the first 2 min of each hour were evaluated for the frequency of IED. Univariate associations with AIs were assessed by Pearson's correlation and by t test. When testing the independent associations, multivariate linear regression was performed. Results: The AIs in patients with left-sided MTLE were 0.40 +/- 0.53 on average (range, -0.83 to +1.0), whereas in right-sided MTLE, they were 0.78 +/- 0.15 (p = 0.029). For the further investigations, we included left-sided MTLE patients only. The median frequency of IED was six per hour (range, 0-240). Higher IED frequency was correlated with left-right shift of lateralization of speech fMRI activity (p = 0.002). Conclusions: Higher left-sided spike frequency in MTLE was associated with a left-right shift of speech representation, suggesting that chronic frequent interictal activity may induce a reorganization of speech lateralization.