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Structural connections of the centromedian nucleus of thalamus and their relevance for neuromodulation in generalized drug-resistant epilepsy: insight from a tractography study
BACKGROUND: Epilepsy is a widespread neurologic disorder and almost one-third of patients suffer from drug-resistant epilepsy (DRE). Neuromodulation targeting the centromediannucleus of the thalamus (CM) has been showing promising results for patients with generalized DRE who are not surgical candid...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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SAGE Publications
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10563482/ https://www.ncbi.nlm.nih.gov/pubmed/37822361 http://dx.doi.org/10.1177/17562864231202064 |
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author | Remore, Luigi G. Rifi, Ziad Nariai, Hiroki Eliashiv, Dawn S. Fallah, Aria Edmonds, Benjamin D. Matsumoto, Joyce H. Salamon, Noriko Tolossa, Meskerem Wei, Wexin Locatelli, Marco Tsolaki, Evangelia C. Bari, Ausaf A. |
author_facet | Remore, Luigi G. Rifi, Ziad Nariai, Hiroki Eliashiv, Dawn S. Fallah, Aria Edmonds, Benjamin D. Matsumoto, Joyce H. Salamon, Noriko Tolossa, Meskerem Wei, Wexin Locatelli, Marco Tsolaki, Evangelia C. Bari, Ausaf A. |
author_sort | Remore, Luigi G. |
collection | PubMed |
description | BACKGROUND: Epilepsy is a widespread neurologic disorder and almost one-third of patients suffer from drug-resistant epilepsy (DRE). Neuromodulation targeting the centromediannucleus of the thalamus (CM) has been showing promising results for patients with generalized DRE who are not surgical candidates. Recently, the effect of CM- deep brain stimulation (DBS) in DRE patients was investigated in the Electrical Stimulation of Thalamus for Epilepsy of Lennox–Gastaut phenotype (ESTEL) trial, a monocentric randomized-controlled study. The same authors described a ‘cold-spot’ and a ‘sweet-spot’, which are defined as the volume of stimulation in the thalamus yielding the least and the best clinical response, respectively. However, it remains unclear which structural connections may contribute to the anti-seizure effect of the stimulation. OBJECTIVE: We investigated the differences in structural connectivity among CM, the sweet-spot and the cold-spot. Furthermore, we tried to validate our results in a cohort of DRE patients who underwent CM-DBS or CM-RNS (responsive neurostimulation). We hypothesized that the sweet-spot would share similar structural connectivity with responder patients. METHODS: By using the software FMRIB Software Library (FSL), probabilistic tractography was performed on 100 subjects from the Human Connectome Project to calculate the probability of connectivity of the whole CM, the sweet-spot and the cold-spot to 45 cortical and subcortical areas. Results among the three seeds were compared with multivariate analysis of variance (MANOVA). Similarly, the structural connectivity of volumes of tissue activated (VTAs) from eight DRE patients was investigated. Patients were divided into responders and non-responders based on the degree of reduction in seizure frequency, and the mean probabilities of connectivity were similarly compared between the two groups. RESULTS: The sweet-spot demonstrated a significantly higher probability of connectivity (p < 0.001) with the precentral gyrus, superior frontal gyrus, and the cerebellum than the whole CM and the cold-spot. Responder patients displayed a higher probability of connectivity with both ipsilateral (p = 0.011) and contralateral cerebellum (p = 0.04) than the non-responders. CONCLUSION: Cerebellar connections seem to contribute to the beneficial effects of CM-neuromodulation in patients with drug-resistant generalized epilepsy. |
format | Online Article Text |
id | pubmed-10563482 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-105634822023-10-11 Structural connections of the centromedian nucleus of thalamus and their relevance for neuromodulation in generalized drug-resistant epilepsy: insight from a tractography study Remore, Luigi G. Rifi, Ziad Nariai, Hiroki Eliashiv, Dawn S. Fallah, Aria Edmonds, Benjamin D. Matsumoto, Joyce H. Salamon, Noriko Tolossa, Meskerem Wei, Wexin Locatelli, Marco Tsolaki, Evangelia C. Bari, Ausaf A. Ther Adv Neurol Disord Original Research BACKGROUND: Epilepsy is a widespread neurologic disorder and almost one-third of patients suffer from drug-resistant epilepsy (DRE). Neuromodulation targeting the centromediannucleus of the thalamus (CM) has been showing promising results for patients with generalized DRE who are not surgical candidates. Recently, the effect of CM- deep brain stimulation (DBS) in DRE patients was investigated in the Electrical Stimulation of Thalamus for Epilepsy of Lennox–Gastaut phenotype (ESTEL) trial, a monocentric randomized-controlled study. The same authors described a ‘cold-spot’ and a ‘sweet-spot’, which are defined as the volume of stimulation in the thalamus yielding the least and the best clinical response, respectively. However, it remains unclear which structural connections may contribute to the anti-seizure effect of the stimulation. OBJECTIVE: We investigated the differences in structural connectivity among CM, the sweet-spot and the cold-spot. Furthermore, we tried to validate our results in a cohort of DRE patients who underwent CM-DBS or CM-RNS (responsive neurostimulation). We hypothesized that the sweet-spot would share similar structural connectivity with responder patients. METHODS: By using the software FMRIB Software Library (FSL), probabilistic tractography was performed on 100 subjects from the Human Connectome Project to calculate the probability of connectivity of the whole CM, the sweet-spot and the cold-spot to 45 cortical and subcortical areas. Results among the three seeds were compared with multivariate analysis of variance (MANOVA). Similarly, the structural connectivity of volumes of tissue activated (VTAs) from eight DRE patients was investigated. Patients were divided into responders and non-responders based on the degree of reduction in seizure frequency, and the mean probabilities of connectivity were similarly compared between the two groups. RESULTS: The sweet-spot demonstrated a significantly higher probability of connectivity (p < 0.001) with the precentral gyrus, superior frontal gyrus, and the cerebellum than the whole CM and the cold-spot. Responder patients displayed a higher probability of connectivity with both ipsilateral (p = 0.011) and contralateral cerebellum (p = 0.04) than the non-responders. CONCLUSION: Cerebellar connections seem to contribute to the beneficial effects of CM-neuromodulation in patients with drug-resistant generalized epilepsy. SAGE Publications 2023-10-10 /pmc/articles/PMC10563482/ /pubmed/37822361 http://dx.doi.org/10.1177/17562864231202064 Text en © The Author(s), 2023 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Research Remore, Luigi G. Rifi, Ziad Nariai, Hiroki Eliashiv, Dawn S. Fallah, Aria Edmonds, Benjamin D. Matsumoto, Joyce H. Salamon, Noriko Tolossa, Meskerem Wei, Wexin Locatelli, Marco Tsolaki, Evangelia C. Bari, Ausaf A. Structural connections of the centromedian nucleus of thalamus and their relevance for neuromodulation in generalized drug-resistant epilepsy: insight from a tractography study |
title | Structural connections of the centromedian nucleus of thalamus and their relevance for neuromodulation in generalized drug-resistant epilepsy: insight from a tractography study |
title_full | Structural connections of the centromedian nucleus of thalamus and their relevance for neuromodulation in generalized drug-resistant epilepsy: insight from a tractography study |
title_fullStr | Structural connections of the centromedian nucleus of thalamus and their relevance for neuromodulation in generalized drug-resistant epilepsy: insight from a tractography study |
title_full_unstemmed | Structural connections of the centromedian nucleus of thalamus and their relevance for neuromodulation in generalized drug-resistant epilepsy: insight from a tractography study |
title_short | Structural connections of the centromedian nucleus of thalamus and their relevance for neuromodulation in generalized drug-resistant epilepsy: insight from a tractography study |
title_sort | structural connections of the centromedian nucleus of thalamus and their relevance for neuromodulation in generalized drug-resistant epilepsy: insight from a tractography study |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10563482/ https://www.ncbi.nlm.nih.gov/pubmed/37822361 http://dx.doi.org/10.1177/17562864231202064 |
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