Cognitive slowing and its underlying neurobiology in temporal lobe epilepsy

Cognitive slowing is a known but comparatively under-investigated neuropsychological complication of the epilepsies in relation to other known cognitive comorbidities such as memory, executive function and language. Here we focus on a novel metric of processing speed, characterize its relative salience compared to other cognitive difficulties in epilepsy, and explore its underlying neurobiological correlates. Research participants included 55 patients with temporal lobe epilepsy (TLE) and 58 healthy controls from the Epilepsy Connectome Project (ECP) who were administered a battery of tests yielding 14 neuropsychological measures, including selected tests from the NIH Toolbox-Cognitive Battery, and underwent 3T MRI and resting state fMRI. TLE patients exhibited a pattern of generalized cognitive impairment with very few lateralized abnormalities. Using the neuropsychological measures, machine learning (Support Vector Machine binary classification model) classified the TLE and control groups with 74% accuracy with processing speed (NIH Toolbox Pattern Comparison Processing Speed Test) the best predictor. In TLE, slower processing speed was associated predominantly with decreased local gyrification in regions including the rostral and caudal middle frontal gyrus, inferior precentral cortex, insula, inferior parietal cortex (angular and supramarginal gyri), lateral occipital cortex, rostral anterior cingulate, and medial orbital frontal regions, as well as three small regions of the temporal lobe. Slower processing speed was also associated with decreased connectivity between the primary visual cortices in both hemispheres and the left supplementary motor area, as well as between the right parieto-occipital sulcus and right middle insular area. Overall, slowed processing speed is an important cognitive comorbidity of TLE associated with altered brain structure and connectivity.