Identifying the neural basis of a language‐impaired phenotype of temporal lobe epilepsy

• Published in: Epilepsia (Copenhagen) Vol. 60; no. 8; pp. 1627 - 1638
• Main Authors: Kaestner, Erik, Reyes, Anny, Macari, Anna Christina, Chang, Yu‐Hsuan, Paul, Brianna M., Hermann, Bruce P., McDonald, Carrie R.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.08.2019
• Subjects: Adult; Anisotropy; Brain - diagnostic imaging; Brain - physiopathology; Case-Control Studies; clinical biomarkers; Cognitive ability; cognitive phenotype; Cortex (temporal); Diffusion Tensor Imaging; Drug Resistant Epilepsy - complications; Drug Resistant Epilepsy - diagnostic imaging; Drug Resistant Epilepsy - physiopathology; Epilepsy; Epilepsy, Temporal Lobe - complications; Epilepsy, Temporal Lobe - diagnostic imaging; Epilepsy, Temporal Lobe - physiopathology; Female; Functional magnetic resonance imaging; Functional Neuroimaging; Genotype & phenotype; Humans; Language; Language Disorders - diagnostic imaging; Language Disorders - etiology; Language Disorders - physiopathology; Language Tests; Magnetic Resonance Imaging; Male; Measuring techniques; neural substrate; Neuroimaging; NMR; Nuclear magnetic resonance; Patients; Phenotype; Phenotypes; Psychology; Seizures; Substantia alba; Superior temporal gyrus; Temporal gyrus; Temporal lobe; diffusion tensor imaging; cognitive phenotype; neural substrate; clinical biomarkers; functional magnetic resonance imaging; neuroimaging
• ISSN: 0013-9580; 1528-1167; 1528-1167
• DOI: 10.1111/epi.16283

Objective To identify neuroimaging and clinical biomarkers associated with a language‐impaired phenotype in refractory temporal lobe epilepsy (TLE). Methods Eighty‐five patients with TLE were characterized as language‐impaired (TLE‐LI) or non–language‐impaired (TLE‐NLI) based on comprehensive neuropsychological testing. Structural magnetic resonance imaging (MRI), diffusion tensor imaging, and functional MRI (fMRI) were obtained in patients and 47 healthy controls (HC). fMRI activations and cortical thickness were calculated within language regions of interest, and fractional anisotropy (FA) was calculated within deep white matter tracts associated with language. Analyses of variance were performed to test for differences among the groups in imaging measures. Receiver operator characteristic curves were used to determine how well different clinical versus imaging measures discriminated TLE‐LI from TLE‐NLI. Results TLE‐LI patients showed significantly less activation within left superior temporal cortex compared to HC and TLE‐NLI, regardless of side of seizure onset. TLE‐LI also showed decreased FA in the inferior longitudinal fasciculus and arcuate fasciculus compared to HC. Cortical thickness did not differ between groups in any region. A model that included language‐related fMRI activations within the superior temporal gyrus, age at onset, and demographic variables was the most predictive of language impairment (area under the curve = 0.80). Significance These findings demonstrate a unique imaging signature associated with a language‐impaired phenotype in TLE, characterized by functional and microstructural alterations within the language network. Reduced left superior temporal activation combined with compromise to language association tracts underlies this phenotype, extending our previous work on cognitive phenotypes that could have implications for treatment‐planning or cognitive progression in TLE.