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

Abstract

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.

Network, clinical and sociodemographic features of cognitive phenotypes in temporal lobe epilepsy

“…In that TLE is a network disorder and the ECP sample represents a more benign profile than our previous refractory group, regional thickness/volume estimates may not be sensitive enough, whereas the GT measures are able to capture group differences. In point of fact, recent work with a specific “language-impaired phenotype” showed that regional measures of superficial white matter compromise did not reveal differences between the language-impaired phenotype and healthy controls, but network-based measures did ( Kaestner et al, 2019 ).…”

“…In this view cognitive variability within an epilepsy syndrome becomes a core focus of investigation. A developing literature has demonstrated the existence of cognitive subtypes within well-characterized epilepsy syndromes, examined most frequently in TLE given the careful study of these patients as part of the presurgical process ( Elverman et al, 2019 , Hermann et al, 2007 , Kaestner et al, 2019 , Reyes et al, 2019 , Rodríguez-Cruces et al, 2018 ). While the overall modal cognitive profile may be one of broader than expected abnormalities, subgroups of patients appear to exist including some with surprisingly intact cognition, some with syndrome-specific cognitive impairment, and others with generalized nonspecific cognitive impairment.…”

“…While the overall modal cognitive profile may be one of broader than expected abnormalities, subgroups of patients appear to exist including some with surprisingly intact cognition, some with syndrome-specific cognitive impairment, and others with generalized nonspecific cognitive impairment. The number of investigations examining neuroimaging correlates of these subgroups is more limited, but with some evidence that increasingly distributed neurobiological abnormalities are associated with increasingly broad cognitive impairments ( Dabbs et al, 2009 , Hermann et al, 2007 , Kaestner et al, 2019 , Reyes et al, 2019 , Rodríguez-Cruces et al, 2018 , Rodríguez-Cruces et al, 2020 ).…”

Addressing neuropsychological diagnostics in adults with epilepsy: Introducing the International Classification of Cognitive Disorders in Epilepsy: The IC CODE Initiative

“…40 Despite the increasing popularity of this comprehensive neuropsychological approach for cognitive subtyping in MCI, a similar method has only recently been applied to patients with epilepsy. 23,45,46 Investigating patients with temporal lobe epilepsy, this diagnostic approach yielded distinct groups of patients (memory-impaired, language-impaired, multidomain, cognitively normal) with unique clinical, cognitive, and neuroimaging profiles. 23 More generally, there have been a modest number of empirical attempts to identify underlying latent cognitive groups in patients with adult epilepsies that have revealed associated neuroimaging correlates and varying prospective cognitive trajectories associated with the identified groups.…”

Disorganization of language and working memory systems in frontal versus temporal lobe epilepsy

“…22, 23, 77, 78 Alteration of frontal function in TLE may emerge as propagated abnormality, and could be mediated by microstructural alterations in perisylvian white matter tracts. 49, 73, 74 During verb generation, there were differences between FLE and TLE in the semantic processing stream, involving posterior temporo-parietal and occipital areas. 69, 79, 80 More marked impairment during tasks with semantic demands thus appears TLE-specific, and correlates with neuropsychological findings.…”