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Altered metabolic connectivity within the limbic cortico-striato-thalamo-cortical circuit in presymptomatic and symptomatic behavioral variant frontotemporal dementia

BACKGROUND: Behavioral variant frontotemporal dementia (bvFTD) is predominantly considered a dysfunction in cortico-cortical transmission, with limited direct investigation of cortical-subcortical transmission. Thus, we aimed to characterize the metabolic connectivity between areas of the limbic cor...

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Autores principales: Liu, Li, Chu, Min, Nie, Binbin, Jiang, Deming, Xie, Kexin, Cui, Yue, Liu, Lin, Kong, Yu, Chen, Zhongyun, Nan, Haitian, Rosa-Neto, Pedro, Wu, Liyong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9814421/
https://www.ncbi.nlm.nih.gov/pubmed/36604747
http://dx.doi.org/10.1186/s13195-022-01157-7
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author Liu, Li
Chu, Min
Nie, Binbin
Jiang, Deming
Xie, Kexin
Cui, Yue
Liu, Lin
Kong, Yu
Chen, Zhongyun
Nan, Haitian
Rosa-Neto, Pedro
Wu, Liyong
author_facet Liu, Li
Chu, Min
Nie, Binbin
Jiang, Deming
Xie, Kexin
Cui, Yue
Liu, Lin
Kong, Yu
Chen, Zhongyun
Nan, Haitian
Rosa-Neto, Pedro
Wu, Liyong
author_sort Liu, Li
collection PubMed
description BACKGROUND: Behavioral variant frontotemporal dementia (bvFTD) is predominantly considered a dysfunction in cortico-cortical transmission, with limited direct investigation of cortical-subcortical transmission. Thus, we aimed to characterize the metabolic connectivity between areas of the limbic cortico-striato-thalamic-cortical (CSTC) circuit in presymptomatic and symptomatic bvFTD patients. METHODS: Thirty-three bvFTD patients and 33 unrelated healthy controls were recruited for this study. Additionally, six asymptomatic carriers of the MAPT P301L mutation were compared with 12 non-carriers who were all from the same family of bvFTD. Each participant underwent neuropsychological assessment, genetic testing, and a hybrid PET/MRI scan. Seed-based metabolic connectivity based on [(18)F]-fluorodeoxyglucose PET between the main components within the limbic CSTC circuit was explored according to the Oxford-GSK-Imanova Striatal Connectivity Atlas. RESULTS: BvFTD patients exhibited reduced metabolic connectivity between the relays in the limbic CSTC circuit, which included the frontal region (ventromedial prefrontal cortex, orbitofrontal cortex, rectus gyrus, and anterior cingulate cortex), the limbic striatum, and thalamus compared to controls. In the bvFTD patients, the involvement of the limbic CSTC circuit was associated with the severity of behavior disruption, as measured by the frontal behavior inventory, the disinhibition subscale, and the apathy subscale. Notably, asymptomatic MAPT carriers had weakened frontostriatal connectivity but enhanced striatothalamus and thalamofrontal connectivity within the limbic CSTC circuit compared with noncarriers. CONCLUSION: These findings suggested that aberrant metabolic connectivity within the limbic CSTC circuit is present in symptomatic and even asymptomatic stages of bvFTD. Thus, metabolic connectivity patterns could be used as a potential biomarker to detect the presymptomatic stage and track disease progression. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13195-022-01157-7.
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spelling pubmed-98144212023-01-06 Altered metabolic connectivity within the limbic cortico-striato-thalamo-cortical circuit in presymptomatic and symptomatic behavioral variant frontotemporal dementia Liu, Li Chu, Min Nie, Binbin Jiang, Deming Xie, Kexin Cui, Yue Liu, Lin Kong, Yu Chen, Zhongyun Nan, Haitian Rosa-Neto, Pedro Wu, Liyong Alzheimers Res Ther Research BACKGROUND: Behavioral variant frontotemporal dementia (bvFTD) is predominantly considered a dysfunction in cortico-cortical transmission, with limited direct investigation of cortical-subcortical transmission. Thus, we aimed to characterize the metabolic connectivity between areas of the limbic cortico-striato-thalamic-cortical (CSTC) circuit in presymptomatic and symptomatic bvFTD patients. METHODS: Thirty-three bvFTD patients and 33 unrelated healthy controls were recruited for this study. Additionally, six asymptomatic carriers of the MAPT P301L mutation were compared with 12 non-carriers who were all from the same family of bvFTD. Each participant underwent neuropsychological assessment, genetic testing, and a hybrid PET/MRI scan. Seed-based metabolic connectivity based on [(18)F]-fluorodeoxyglucose PET between the main components within the limbic CSTC circuit was explored according to the Oxford-GSK-Imanova Striatal Connectivity Atlas. RESULTS: BvFTD patients exhibited reduced metabolic connectivity between the relays in the limbic CSTC circuit, which included the frontal region (ventromedial prefrontal cortex, orbitofrontal cortex, rectus gyrus, and anterior cingulate cortex), the limbic striatum, and thalamus compared to controls. In the bvFTD patients, the involvement of the limbic CSTC circuit was associated with the severity of behavior disruption, as measured by the frontal behavior inventory, the disinhibition subscale, and the apathy subscale. Notably, asymptomatic MAPT carriers had weakened frontostriatal connectivity but enhanced striatothalamus and thalamofrontal connectivity within the limbic CSTC circuit compared with noncarriers. CONCLUSION: These findings suggested that aberrant metabolic connectivity within the limbic CSTC circuit is present in symptomatic and even asymptomatic stages of bvFTD. Thus, metabolic connectivity patterns could be used as a potential biomarker to detect the presymptomatic stage and track disease progression. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13195-022-01157-7. BioMed Central 2023-01-05 /pmc/articles/PMC9814421/ /pubmed/36604747 http://dx.doi.org/10.1186/s13195-022-01157-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Liu, Li
Chu, Min
Nie, Binbin
Jiang, Deming
Xie, Kexin
Cui, Yue
Liu, Lin
Kong, Yu
Chen, Zhongyun
Nan, Haitian
Rosa-Neto, Pedro
Wu, Liyong
Altered metabolic connectivity within the limbic cortico-striato-thalamo-cortical circuit in presymptomatic and symptomatic behavioral variant frontotemporal dementia
title Altered metabolic connectivity within the limbic cortico-striato-thalamo-cortical circuit in presymptomatic and symptomatic behavioral variant frontotemporal dementia
title_full Altered metabolic connectivity within the limbic cortico-striato-thalamo-cortical circuit in presymptomatic and symptomatic behavioral variant frontotemporal dementia
title_fullStr Altered metabolic connectivity within the limbic cortico-striato-thalamo-cortical circuit in presymptomatic and symptomatic behavioral variant frontotemporal dementia
title_full_unstemmed Altered metabolic connectivity within the limbic cortico-striato-thalamo-cortical circuit in presymptomatic and symptomatic behavioral variant frontotemporal dementia
title_short Altered metabolic connectivity within the limbic cortico-striato-thalamo-cortical circuit in presymptomatic and symptomatic behavioral variant frontotemporal dementia
title_sort altered metabolic connectivity within the limbic cortico-striato-thalamo-cortical circuit in presymptomatic and symptomatic behavioral variant frontotemporal dementia
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9814421/
https://www.ncbi.nlm.nih.gov/pubmed/36604747
http://dx.doi.org/10.1186/s13195-022-01157-7
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