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dc.contributor.authorSkouras, Stavros
dc.contributor.authorTorner Ribé, Jordi
dc.contributor.authorAlpiste Penalba, Francesc
dc.contributor.authorMolinuevo, José Luis
dc.contributor.otherUniversitat Politècnica de Catalunya. Departament d'Expressió Gràfica a l'Enginyeria
dc.date.accessioned2020-04-28T12:42:39Z
dc.date.available2021-02-20T01:29:12Z
dc.date.issued2020-02-24
dc.identifier.citationSkouras, S. [et al.]. Earliest amyloid and tau deposition modulate the influence of limbic networks during closed-loop hippocampal downregulation. "Brain", 24 Febrer 2020, vol. 143, núm. 3, p. 976-992.
dc.identifier.issn0006-8950
dc.identifier.urihttp://hdl.handle.net/2117/185457
dc.description.abstractResearch into hippocampal self-regulation abilities may help determine the clinical significance of hippocampal hyperactivity throughout the pathophysiological continuum of Alzheimer’s disease. In this study, we aimed to identify the effects of amyloid-ß peptide 42 (amyloid-ß42) and phosphorylated tau on the patterns of functional connectomics involved in hippocampal downregulation. We identified 48 cognitively unimpaired participants (22 with elevated CSF amyloid-ß peptide 42 levels, 15 with elevated CSF phosphorylated tau levels, mean age of 62.705 ± 4.628 years), from the population-based ‘Alzheimer’s and Families’ study, with baseline MRI, CSF biomarkers, APOE genotyping and neuropsychological evaluation. We developed a closed-loop, real-time functional MRI neurofeedback task with virtual reality and tailored it for training downregulation of hippocampal subfield cornu ammonis 1 (CA1). Neurofeedback performance score, cognitive reserve score, hippocampal volume, number of apolipoprotein e4 alleles and sex were controlled for as confounds in all cross-sectional analyses. First, using voxel-wise multiple regression analysis and controlling for CSF biomarkers, we identified the effect of healthy ageing on eigenvector centrality, a measure of each voxel’s overall influence based on iterative whole-brain connectomics, during hippocampal CA1 downregulation. Then, controlling for age, we identified the effects of abnormal CSF amyloid-ß42 and phosphorylated tau levels on eigenvector centrality during hippocampal CA1 downregulation. Across subjects, our main findings during hippocampal downregulation were: (i) in the absence of abnormal biomarkers, age correlated with eigenvector centrality negatively in the insula and midcingulate cortex, and positively in the inferior temporal gyrus; (ii) abnormal CSF amyloid-ß42 (<1098) correlated negatively with eigenvector centrality in the anterior cingulate cortex and primary motor cortex; and (iii) abnormal CSF phosphorylated tau levels (>19.2) correlated with eigenvector centrality positively in the ventral striatum, anterior cingulate and somatosensory cortex, and negatively in the precuneus and orbitofrontal cortex. During resting state functional MRI, similar eigenvector centrality patterns in the cingulate had previously been associated to CSF biomarkers in mild cognitive impairment and dementia patients. Using the developed closed-loop paradigm, we observed such patterns, which are characteristic of advanced disease stages, during a much earlier presymptomatic phase. In the absence of CSF biomarkers, our non-invasive, interactive, adaptive and gamified neuroimaging procedure may provide important information for clinical prognosis and monitoring of therapeutic efficacy. We have released the developed paradigm and analysis pipeline as open-source software to facilitate replication studies.
dc.format.extent17 p.
dc.language.isoeng
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Spain
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
dc.subjectÀrees temàtiques de la UPC::Informàtica::Aplicacions de la informàtica
dc.subject.lcshBioengineering
dc.subject.otherAmyloid-ß42
dc.subject.otherp-tau
dc.subject.otherrt-fMRI
dc.subject.otherECM
dc.subject.otherCA1
dc.titleEarliest amyloid and tau deposition modulate the influence of limbic networks during closed-loop hippocampal downregulation
dc.typeArticle
dc.subject.lemacAlzheimer, Malaltia d'
dc.subject.lemacBioenginyeria
dc.contributor.groupUniversitat Politècnica de Catalunya. LAM - Laboratori d'Aplicacions Multimèdia i TIC
dc.identifier.doi10.1093/brain/awaa011
dc.description.peerreviewedPeer Reviewed
dc.relation.publisherversionhttps://academic.oup.com/brain/article/143/3/976/5753887
dc.rights.accessOpen Access
local.identifier.drac27072519
dc.description.versionPostprint (author's final draft)
local.citation.authorSkouras, S.; Jordi Torner; Alpiste, F.; Molinuevo, J.
local.citation.publicationNameBrain
local.citation.volume143
local.citation.number3
local.citation.startingPage976
local.citation.endingPage992


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