Dataset Information

Cognitive slowing and its underlying neurobiology in temporal lobe epilepsy.

ABSTRACT: 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.

SUBMITTER: Hwang G

PROVIDER: S-EPMC6650302 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Cognitive slowing and its underlying neurobiology in temporal lobe epilepsy.

Hwang Gyujoon G Dabbs Kevin K Conant Lisa L Nair Veena A VA Mathis Jed J Almane Dace N DN Nencka Andrew A Birn Rasmus R Humphries Colin C Raghavan Manoj M DeYoe Edgar A EA Struck Aaron F AF Maganti Rama R Binder Jeffrey R JR Meyerand Elizabeth E Prabhakaran Vivek V Hermann Bruce B

Cortex; a journal devoted to the study of the nervous system and behavior 20190305

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 hea ...[more]

PMID: 30927560

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Project description:This study explored the taxonomy of cognitive impairment within temporal lobe epilepsy and characterized the sociodemographic, clinical and neurobiological correlates of identified cognitive phenotypes. 111 temporal lobe epilepsy patients and 83 controls (mean ages 33 and 39, 57% and 61% female, respectively) from the Epilepsy Connectome Project underwent neuropsychological assessment, clinical interview, and high resolution 3T structural and resting-state functional MRI. A comprehensive neuropsychological test battery was reduced to core cognitive domains (language, memory, executive, visuospatial, motor speed) which were then subjected to cluster analysis. The resulting cognitive subgroups were compared in regard to sociodemographic and clinical epilepsy characteristics as well as variations in brain structure and functional connectivity. Three cognitive subgroups were identified (intact, language/memory/executive function impairment, generalized impairment) which differed significantly, in a systematic fashion, across multiple features. The generalized impairment group was characterized by an earlier age at medication initiation (P < 0.05), fewer patient (P < 0.001) and parental years of education (P < 0.05), greater racial diversity (P < 0.05), and greater number of lifetime generalized seizures (P < 0.001). The three groups also differed in an orderly manner across total intracranial (P < 0.001) and bilateral cerebellar cortex volumes (P < 0.01), and rate of bilateral hippocampal atrophy (P < 0.014), but minimally in regional measures of cortical volume or thickness. In contrast, large-scale patterns of cortical-subcortical covariance networks revealed significant differences across groups in global and local measures of community structure and distribution of hubs. Resting-state fMRI revealed stepwise anomalies as a function of cluster membership, with the most abnormal patterns of connectivity evident in the generalized impairment group and no significant differences from controls in the cognitively intact group. Overall, the distinct underlying cognitive phenotypes of temporal lobe epilepsy harbor systematic relationships with clinical, sociodemographic and neuroimaging correlates. Cognitive phenotype variations in patient and familial education and ethnicity, with linked variations in total intracranial volume, raise the question of an early and persisting socioeconomic-status related neurodevelopmental impact, with additional contributions of clinical epilepsy factors (e.g., lifetime generalized seizures). The neuroimaging features of cognitive phenotype membership are most notable for disrupted large scale cortical-subcortical networks and patterns of functional connectivity with bilateral hippocampal and cerebellar atrophy. The cognitive taxonomy of temporal lobe epilepsy appears influenced by features that reflect the combined influence of socioeconomic, neurodevelopmental and neurobiological risk factors.

Project description:Most patients with pharmacoresistant mesial temporal lobe epilepsy (MTLE) have hippocampal sclerosis on the postoperative histopathological examination. Although most patients with MTLE do not refer to a family history of the disease, familial forms of MTLE have been reported. We studied surgical specimens from patients with MTLE who had epilepsy surgery for medically intractable seizures. We assessed and compared gene expression profiles of the tissue lesion found in patients with familial MTLE (n = 3) and sporadic MTLE (n = 5). In addition, we used data from control hippocampi obtained from a public database (n = 7). We obtained expression profiles using the Human Genome U133 Plus 2.0 (Affymetrix) microarray platform. Overall, the molecular profile identified in familial MTLE differed from that in sporadic MTLE. In the tissue of patients with familial MTLE, we found an over-representation of the biological pathways related to protein response, mRNA processing, and synaptic plasticity and function. In sporadic MTLE, the gene expression profile suggests that the inflammatory response is highly activated. In addition, we found enrichment of gene sets involved in inflammatory cytokines and mediators and chemokine receptor pathways in both groups. However, in sporadic MTLE, we also found enrichment of epidermal growth factor signaling, prostaglandin synthesis and regulation, and microglia pathogen phagocytosis pathways. Furthermore, based on the gene expression signatures, we identified different potential compounds to treat patients with familial and sporadic MTLE. To our knowledge, this is the first study assessing the mRNA profile in surgical tissue obtained from patients with familial MTLE and comparing it with sporadic MTLE. Our results clearly show that, despite phenotypic similarities, both forms of MTLE present distinct molecular signatures, thus suggesting different underlying molecular mechanisms that may require distinct therapeutic approaches.

Dataset Information

Cognitive slowing and its underlying neurobiology in temporal lobe epilepsy.

Publications

Cognitive slowing and its underlying neurobiology in temporal lobe epilepsy.

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