Abstract
SummaryObjectiveTo investigate the effects of sodium channel–blocking antiepileptic drugs (AEDs) on functional magnetic resonance imaging (fMRI) language network activations in patients with focal epilepsy.MethodsIn a retrospective study, we identified patients who were treated at the time of language fMRI scanning with either carbamazepine (CBZ; n = 42) or lamotrigine (LTG; n = 42), but not another sodium channel–blocking AED. We propensity‐matched 42 patients taking levetiracetam (LEV) as “patient‐controls” and included further 42 age‐ and gender‐matched healthy controls. After controlling for age, age at onset of epilepsy, gender, and antiepileptic comedications, we compared verbal fluency fMRI activations between groups and out‐of‐scanner psychometric measures of verbal fluency.ResultsPatients on CBZ performed less well on a verbal fluency tests than those taking LTG or LEV. Compared to either LEV‐treated patients or controls, patients taking CBZ showed decreased activations in left inferior frontal gyrus and patients on LTG showed abnormal deactivations in frontal and parietal default mode areas. All patient groups showed fewer activations in the putamen bilaterally compared to controls. In a post hoc analysis, out‐of‐scanner fluency scores correlated positively with left putamen activation.SignificanceOur study provides evidence of AED effects on the functional neuroanatomy of language, which might explain subtle language deficits in patients taking otherwise well‐tolerated sodium channel–blocking agents. Patients on CBZ showed dysfunctional frontal activation and more pronounced impairment of performance than patients taking LTG, which was associated only with failure to deactivate task‐negative networks. As previously shown for working memory, LEV treatment did not affect functional language networks.
Highlights
Lamotrigine (LTG) and carbamazepine (CBZ) are both effective antiepileptic drugs (AEDs) and well-tolerated in epilepsy patients.[1]
The verbal fluency functional magnetic resonance imaging (fMRI) task usually elicits the activation of frontal lobe areas, the dominant inferior frontal gyrus (IFG), middle frontal gyrus (MFG), anterior cingulate, and precentral cortices, as well as the insular, superior temporal, and parietal cortices and the cerebellum.[5,6,7]
For the second-level analysis, we introduced control subjects (CTR) and entered activation contrasts for each patient and control into a full factorial design with group as a factor (CBZ, LEV, LTG, CTR) and age, gender, and laterality index (LI) as regressors
Summary
Lamotrigine (LTG) and carbamazepine (CBZ) are both effective antiepileptic drugs (AEDs) and well-tolerated in epilepsy patients.[1]. In cognitive functional magnetic resonance imaging (fMRI), consistent and reproducible patterns of activation and deactivation are elicited by goal-directed tasks, including language and memory. The default mode network (DMN) represents a set of brain regions that is commonly deactivated during goal-directed tasks and has been traditionally associated with mind-wandering and envisioning the future.[3,4] The verbal fluency fMRI task usually elicits the activation of frontal lobe areas, the dominant inferior frontal gyrus (IFG), middle frontal gyrus (MFG), anterior cingulate, and precentral cortices, as well as the insular, superior temporal, and parietal cortices and the cerebellum.[5,6,7] Its relatively low demand makes it an important tool for the assessment and lateralization of language function for presurgical evaluation.[7,8]
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