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1.
Epilepsia ; 65(6): 1756-1767, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38517477

RESUMO

OBJECTIVE: Focal to bilateral tonic-clonic seizures (FBTCS) represent a challenging subtype of focal temporal lobe epilepsy (TLE) in terms of both severity and treatment response. Most studies have focused on regional brain analysis that is agnostic to the distribution of white matter (WM) pathways associated with a node. We implemented a more selective, edge-wise approach that allowed for identification of the individual connections unique to FBTCS. METHODS: T1-weighted and diffusion-weighted images were obtained from 22 patients with solely focal seizures (FS), 43 FBTCS patients, and 65 age/sex-matched healthy participants (HPs), yielding streamline (STR) connectome matrices. We used diffusion tensor-derived STRs in an edge-wise approach to determine specific structural connectivity changes associated with seizure generalization in FBTCS compared to matched FS and HPs. Graph theory metrics were computed on both node- and edge-based connectivity matrices. RESULTS: Edge-wise analyses demonstrated that all significantly abnormal cross-hemispheric connections belonged to the FBTCS group. Abnormal connections associated with FBTCS were mostly housed in the contralateral hemisphere, with graph metric values generally decreased compared to HPs. In FBTCS, the contralateral amygdala showed selective decreases in the structural connection pathways to the contralateral frontal lobe. Abnormal connections in TLE involved the amygdala, with the ipsilateral side showing increases and the contralateral decreases. All the FS findings indicated higher graph metrics for connections involving the ipsilateral amygdala. Data also showed that some FBTCS connectivity effects are moderated by aging, recent seizure frequency, and longer illness duration. SIGNIFICANCE: Data showed that not all STR pathways are equally affected by the seizure propagation of FBTCS. We demonstrated two key biases, one indicating a large role for the amygdala in the propagation of seizures, the other pointing to the prominent role of cross-hemispheric and contralateral hemisphere connections in FBTCS. We demonstrated topographic reorganization in FBTCS, pointing to the specific WM tracts involved.


Assuntos
Convulsões , Substância Branca , Humanos , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Feminino , Masculino , Adulto , Convulsões/diagnóstico por imagem , Convulsões/patologia , Convulsões/fisiopatologia , Pessoa de Meia-Idade , Conectoma/métodos , Imagem de Tensor de Difusão/métodos , Adulto Jovem , Vias Neurais/diagnóstico por imagem , Vias Neurais/patologia , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/patologia , Imageamento por Ressonância Magnética/métodos
2.
Neurology ; 103(7): e209800, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39250744

RESUMO

BACKGROUND AND OBJECTIVES: Despite their temporal lobe pathology, a significant subgroup of patients with temporal lobe epilepsy (TLE) is able to maintain normative cognitive functioning. In this study, we identify patients with TLE with intact vs impaired neurocognitive profiles and interrogate for the presence of both normative and highly individual intrinsic connectivity networks (ICNs)-all toward understanding the transition from impaired to intact neurocognitive status. METHODS: This retrospective cross-sectional study included patients with TLE and matched healthy controls (HCs) from the Thomas Jefferson Comprehensive Epilepsy Center. Functional MRI data were decomposed using independent component analysis to obtain individualized ICNs. In this article, we calculated the degree of match between individualized ICNs and canonical ICNs (e.g., 17 resting-state networks by Yeo et al.) and divided each participant's ICNs into normative or non-normative status based on the degree of match. RESULTS: 100 patients with TLE (mean age 42.0 [SD: 13.7] years, 47 women) and 92 HCs were included in this study. We found that the individualized networks matched to the canonical networks less well in the cognitively impaired (n = 24) compared with the cognitively intact (n = 63) patients with TLE by 2-way mixed-measures analysis of variance (impaired vs intact mean difference [MD] -0.165 [-0.317, -0.013], p = 0.028). The cognitively impaired patients showed significant abnormalities in the profiles of both normative (impaired vs intact MD -0.537 [-0.998, -0.076], p = 0.017, intact vs HC MD -0.221 [-0.536, 0.924], p = 0.220, and impaired vs HC MD -0.759 [-1.200, -0.319], p < 0.001) and non-normative networks (impaired vs intact MD 0.484 [0.030, 0.937], p = 0.033, intact vs HC MD 0.369 [0.059, 0.678], p = 0.014, and impaired vs HC MD 0.853 [0.419, 1.286], p < 0.001) while the intact patients showed abnormalities only in non-normative networks. At the same time, we found that normative networks held a strong, positive association with the neuropsychological measures, with this association negative in non-normative networks. DISCUSSION: Our data demonstrated that significant cognitive deficits are associated with the status of both canonical and highly individual ICNs, making clear that the transition from intact to impaired cognitive status is not simply the result of disruption to normative brain networks.


Assuntos
Cognição , Epilepsia do Lobo Temporal , Imageamento por Ressonância Magnética , Rede Nervosa , Humanos , Epilepsia do Lobo Temporal/fisiopatologia , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/psicologia , Feminino , Masculino , Adulto , Estudos Transversais , Pessoa de Meia-Idade , Estudos Retrospectivos , Cognição/fisiologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Testes Neuropsicológicos
3.
Neuroimage Clin ; 38: 103387, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37023491

RESUMO

Despite the effectiveness of surgical interventions for the treatment of intractable focal temporal lobe epilepsy (TLE), the substrates that support good outcomes are poorly understood. While algorithms have been developed for the prediction of either seizure or cognitive/psychiatric outcomes alone, no study has reported on the functional and structural architecture that supports joint outcomes. We measured key aspects of pre-surgical whole brain functional/structural network architecture and evaluated their ability to predict post-operative seizure control in combination with cognitive/psychiatric outcomes. Pre-surgically, we identified the intrinsic connectivity networks (ICNs) unique to each person through independent component analysis (ICA), and computed: (1) the spatial-temporal match between each person's ICA components and established, canonical ICNs, (2) the connectivity strength within each identified person-specific ICN, (3) the gray matter (GM) volume underlying the person-specific ICNs, and (4) the amount of variance not explained by the canonical ICNs for each person. Post-surgical seizure control and reliable change indices of change (for language [naming, phonemic fluency], verbal episodic memory, and depression) served as binary outcome responses in random forest (RF) models. The above functional and structural measures served as input predictors. Our empirically derived ICN-based measures customized to the individual showed that good joint seizure and cognitive/psychiatric outcomes depended upon higher levels of brain reserve (GM volume) in specific networks. In contrast, singular outcomes relied on systematic, idiosyncratic variance in the case of seizure control, and the weakened pre-surgical presence of functional ICNs that encompassed the ictal temporal lobe in the case of cognitive/psychiatric outcomes. Our data made clear that the ICNs differed in their propensity to provide reserve for adaptive outcomes, with some providing structural (brain), and others functional (cognitive) reserve. Our customized methodology demonstrated that when substantial unique, patient-specific ICNs are present prior to surgery there is a reliable association with poor post-surgical seizure control. These ICNs are idiosyncratic in that they did not match the canonical, normative ICNs and, therefore, could not be defined functionally, with their location likely varying by patient. This important finding suggested the level of highly individualized ICN's in the epileptic brain may signal the emergence of epileptogenic activity after surgery.


Assuntos
Epilepsia do Lobo Temporal , Memória Episódica , Humanos , Imageamento por Ressonância Magnética/métodos , Rede Nervosa , Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , Encéfalo/fisiologia , Convulsões
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