Functional connectivity and language impairment in cryptogenic localization-related epilepsy

BACKGROUND: An often underestimated cognitive morbidity in patients with epilepsy is language dysfunction. To investigate the neuronal mechanisms underlying neuropsychological language impairment, activation maps and functional connectivity networks were studied by fMRI of language. METHOD: Fifty-two patients with cryptogenic localization-related epilepsy and 27 healthy controls underwent neuropsychological assessment of IQ, word fluency, and text reading. fMRI was performed with a standard covert word-generation and text-reading paradigm. Functional connectivity analysis comprised cross-correlation of signal time series of the characteristic and most strongly activated regions involved in the language tasks. RESULTS: After careful selection, 34 patients and 20 healthy controls were found eligible for analysis. Patients displayed lower IQ, lower fluency word count, and lower number of words correctly read compared to controls. fMRI activation maps did not differ significantly between patients and controls. For the word-generation paradigm, patients with epilepsy had significantly lower functional connectivity than controls in the prefrontal network. Patients performing worse on the word-fluency test demonstrated a significantly lower mean functional connectivity than controls. Text reading demonstrated lower functional connectivity in patients with epilepsy in the frontotemporal network. Similarly, lower mean functional connectivity was observed in patients with lowest reading performance compared to controls. A relation between reduced functional connectivity and performance on word-fluency and text-reading tests was demonstrated in epilepsy patients. CONCLUSION: Impaired performance on language assessment in epilepsy patients is associated with loss of functional connectivity in the cognitive language networks.