{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T06:21:57Z","timestamp":1785565317812,"version":"3.56.0"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>Friedreich\u2019s ataxia (FRDA) is a severe multisystemic disorder caused by a deficiency of the mitochondrial protein frataxin. While some aspects of FRDA pathology are developmental, the causes underlying the steady progression are unclear. The inaccessibility of key affected tissues to sampling is a main hurdle. Skeletal muscle displays a disease phenotype and may be sampled <jats:italic>in vivo<\/jats:italic> to address open questions on FRDA pathophysiology. Thus, we performed a quantitative mass spectrometry-based proteomics analysis in gastrocnemius skeletal muscle biopsies from genetically confirmed FRDA patients (<jats:italic>n<\/jats:italic> = 5) and controls. Obtained data files were processed using Proteome Discoverer and searched by Sequest HT engine against a UniProt human reference proteome database. Comparing skeletal muscle proteomics profiles between FRDA and controls, we identified 228 significant differentially expressed (DE) proteins, of which 227 were downregulated in FRDA. Principal component analysis showed a clear separation between FRDA and control samples. Interactome analysis revealed clustering of DE proteins in oxidative phosphorylation, ribosomal elements, mitochondrial architecture control, and fission\/fusion pathways. DE findings in the muscle-specific proteomics suggested a shift toward fast-twitching glycolytic fibers. Notably, most DE proteins (169\/228, 74%) are target of the transcription factor nuclear factor-erythroid 2. Our data corroborate a mitochondrial biosignature of FRDA, which extends beyond a mere oxidative phosphorylation failure. Skeletal muscle proteomics highlighted a derangement of mitochondrial architecture and maintenance pathways and a likely adaptive metabolic shift of contractile proteins. The present findings are relevant for the design of future therapeutic strategies and highlight the value of skeletal muscle-omics as disease state readout in FRDA.<\/jats:p>","DOI":"10.3389\/fnins.2023.1289027","type":"journal-article","created":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T10:44:15Z","timestamp":1698749055000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Skeletal muscle proteome analysis underpins multifaceted mitochondrial dysfunction in Friedreich\u2019s ataxia"],"prefix":"10.3389","volume":"17","author":[{"given":"Elisabetta","family":"Indelicato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Faserl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Amprosi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Nachbauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Wanschitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Sarg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Boesch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1083\/JCB.200204081","article-title":"Rab32 is an A-kinase anchoring protein and participates in mitochondrial dynamics.","volume":"158","author":"Alto","year":"2002","journal-title":"J. Cell Biol."},{"key":"B2","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1093\/hmg\/9.2.275","article-title":"Clinical, biochemical and molecular genetic correlations in Friedreich\u2019s ataxia.","volume":"9","author":"Bradley","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"3768","DOI":"10.1016\/S0021-9258(18)61421-8","article-title":"The journal op biological chemistry adult forms of the Ca2+ATPase of sarcoplasmic reticulum expression in developing skeletal muscle*.","volume":"262","author":"Brandls","year":"1987","journal-title":"J. Biol. Chem."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1126\/science.271.5254.1423","article-title":"Friedreich\u2019s ataxia: Autosomal recessive disease caused by an intronic GAA triplet repeat expansion.","volume":"271","author":"Campuzano","year":"1996","journal-title":"Science."},{"key":"B5","doi-asserted-by":"publisher","first-page":"12321","DOI":"10.1073\/PNAS.192449599","article-title":"Inhibition of Fe-S cluster biosynthesis decreases mitochondrial iron export: Evidence that Yfh1p affects Fe-S cluster synthesis.","volume":"99","author":"Chen","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B6","doi-asserted-by":"publisher","first-page":"16958","DOI":"10.1016\/S0021-9258(19)85287-0","article-title":"Isolation and analysis of the gene and cDNA for a human Mu class glutathione S-transferase, GSTM4.","volume":"268","author":"Comstock","year":"1993","journal-title":"J. Biol. Chem."},{"key":"B7","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1002\/ANA.22526","article-title":"A gene expression phenotype in lymphocytes from friedreich ataxia patients.","volume":"70","author":"Coppola","year":"2011","journal-title":"Ann. Neurol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"2452","DOI":"10.1093\/HMG\/DDP183","article-title":"Functional genomic analysis of frataxin deficiency reveals tissue-specific alterations and identifies the PPAR\u03b3 pathway as a therapeutic target in Friedreich\u2019s ataxia.","volume":"18","author":"Coppola","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcad007","article-title":"Proprioceptors-enriched neuronal cultures from induced pluripotent stem cells from Friedreich ataxia patients show altered transcriptomic and proteomic profiles, abnormal neurite extension, and impaired electrophysiological properties.","volume":"5","author":"Dionisi","year":"2023","journal-title":"Brain Commun."},{"key":"B10","doi-asserted-by":"publisher","first-page":"3271","DOI":"10.1089\/SCD.2013.0126","article-title":"Induced pluripotent stem cells from friedreich ataxia patients fail to upregulate frataxin during in vitro differentiation to peripheral sensory neurons.","volume":"22","author":"Eigentler","year":"2013","journal-title":"Stem Cells Dev."},{"key":"B11","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1177\/088307380201700612","article-title":"Friedreich\u2019s ataxia associated with mitochondrial myopathy: Clinicopathologic report.","volume":"17","author":"Gallagher","year":"2002","journal-title":"J Child Neurol."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1371\/JOURNAL.PONE.0017827","article-title":"MISC-1\/OGC links mitochondrial metabolism, apoptosis and insulin secretion.","volume":"6","author":"Gallo","year":"2011","journal-title":"PLoS One"},{"key":"B13","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1111\/jnc.12303","article-title":"Mitochondrial pathophysiology in Friedreich\u2019s ataxia.","volume":"126","author":"Gonz Alez-Cabo","year":"2013","journal-title":"J. Neurochem."},{"key":"B14","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1111\/JNC.12303","article-title":"Mitochondrial pathophysiology in Friedreich\u2019s ataxia.","volume":"126","author":"Gonz\u00e1lez-Cabo","year":"2013","journal-title":"J. Neurochem."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.1007\/S13311-019-00764-X","article-title":"Molecular mechanisms and therapeutics for the GAA\u22c5TTC expansion disease friedreich ataxia.","volume":"16","author":"Gottesfeld","year":"2019","journal-title":"Neurotherapeutics."},{"key":"B16","doi-asserted-by":"publisher","first-page":"4281","DOI":"10.1073\/PNAS.1909814117","article-title":"Decision between mitophagy and apoptosis by Parkin via VDAC1 ubiquitination.","volume":"117","author":"Ham","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2473","DOI":"10.1096\/FJ.14-257717","article-title":"Increasing mitochondrial muscle fatty acid oxidation induces skeletal muscle remodeling toward an oxidative phenotype.","volume":"29","author":"H\u00e9nique","year":"2015","journal-title":"FASEB J."},{"key":"B18","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1093\/BRAIN\/AWM272","article-title":"Mutation of OPA1 causes dominant optic atrophy with external ophthalmoplegia, ataxia, deafness and multiple mitochondrial DNA deletions: A novel disorder of mtDNA maintenance.","volume":"131","author":"Hudson","year":"2008","journal-title":"Brain"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/FNINS.2022.885313\/BIBTEX","article-title":"Cerebrospinal fluid proteomics in friedreich ataxia reveals markers of neurodegeneration and neuroinflammation.","volume":"16","author":"Imbault","year":"2022","journal-title":"Front. Neurosci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1080\/21678707.2018.1409109","article-title":"Emerging therapeutics for the treatment of Friedreich\u2019s ataxia.","volume":"6","author":"Indelicato","year":"2018","journal-title":"Expert Opin. Orphan Drugs"},{"key":"B21","doi-asserted-by":"publisher","first-page":"2241","DOI":"10.1093\/HMG\/DDAD051","article-title":"Skeletal muscle transcriptomics dissects the pathogenesis of Friedreich\u2019s ataxia.","volume":"32","author":"Indelicato","year":"2023","journal-title":"Hum. Mol. Genet."},{"key":"B22","doi-asserted-by":"crossref","first-page":"3331","DOI":"10.1093\/hmg\/ddg349","article-title":"Reduction in frataxin causes progressive accumulation of mitochondrial damage.","volume":"12","author":"Karthikeyan","year":"2023","journal-title":"Hum. Mol. Genet."},{"key":"B23","doi-asserted-by":"crossref","DOI":"10.3390\/microorganisms11102487","article-title":"Enzymatic cleavage of Stx2a in the gut and identification of pancreatic elastase and trypsin as possible main cleavers.","volume":"11","author":"Kellnerov\u00e1","year":"2023","journal-title":"Microorganisms"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0116396","article-title":"The pathogenesis of cardiomyopathy in Friedreich ataxia.","volume":"10","author":"Koeppen","year":"","journal-title":"PLoS One"},{"key":"B25","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1097\/NEN.0000000000000160","article-title":"Friedreich ataxia: Failure of GABA-ergic and glycinergic synaptic transmission in the dentate nucleus.","volume":"74","author":"Koeppen","year":"","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1093\/JNEN\/NLX087","article-title":"Friedreich ataxia: Developmental failure of the dorsal root entry zone.","volume":"76","author":"Koeppen","year":"2017","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1846","DOI":"10.1074\/JBC.RA118.006515","article-title":"Transcriptional profiling of isogenic Friedreich ataxia neurons and effect of an HDAC inhibitor on disease signatures.","volume":"294","author":"Lai","year":"2019","journal-title":"J. Biol. Chem."},{"key":"B28","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1007\/s40265-023-01874-9","article-title":"Omaveloxolone: First approval.","volume":"83","author":"Lee","year":"2023","journal-title":"Drugs"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1093\/DATABASE\/BAAC083","article-title":"TFLink: An integrated gateway to access transcription factor\u2013target gene interactions for multiple species.","volume":"2022","author":"Liska","year":"2022","journal-title":"Database"},{"key":"B30","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/J.CELL.2016.03.014","article-title":"On the dependency of cellular protein levels on mRNA abundance.","volume":"165","author":"Liu","year":"2016","journal-title":"Cell"},{"key":"B31","doi-asserted-by":"publisher","first-page":"11492","DOI":"10.1073\/PNAS.96.20.11492","article-title":"Deficit of in vivo mitochondrial ATP production in patients with Friedreich ataxia.","volume":"96","author":"Lodi","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B32","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1093\/jnen\/nlz029","article-title":"Neurogenic muscle biopsy findings are common in mitochondrial myopathy.","volume":"78","author":"Lu","year":"2019","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1042\/NS20200093","article-title":"Mitochondrial and metabolic dysfunction in friedreich ataxia: Update on pathophysiological relevance and clinical interventions.","volume":"5","author":"Lynch","year":"2021","journal-title":"Neuronal Signal."},{"key":"B34","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1002\/ana.25934","article-title":"Safety and efficacy of omaveloxolone in friedreich ataxia (MOXIe Study).","volume":"89","author":"Lynch","year":"2021","journal-title":"Ann. Neurol."},{"key":"B35","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1177\/0883073812453498","article-title":"Unanswered questions in Friedreich ataxia.","volume":"27","author":"Lynch","year":"2012","journal-title":"J. Child Neurol."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/S41467-020-17954-3","article-title":"Frataxin gene editing rescues Friedreich\u2019s ataxia pathology in dorsal root ganglia organoid-derived sensory neurons.","volume":"11","author":"Mazzara","year":"2020","journal-title":"Nat. Commun."},{"key":"B37","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1097\/NEN.0B013E31825FED76","article-title":"Skeletal muscle involvement in friedreich ataxia and potential effects of recombinant human erythropoietin administration on muscle regeneration and neovascularization.","volume":"71","author":"Nachbauer","year":"2012","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1242\/DMM.030536","article-title":"Comprehensive analysis of gene expression patterns in Friedreich\u2019s ataxia fibroblasts by RNA sequencing reveals altered levels of protein synthesis factors and solute carriers.","volume":"10","author":"Napierala","year":"2017","journal-title":"Dis. Model. Mech."},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/J.MCPRO.2021.100094","article-title":"Reverse phase protein array reveals correlation of retinoic acid metabolism with cardiomyopathy in Friedreich\u2019s ataxia.","volume":"20","author":"Napierala","year":"2021","journal-title":"Mol. Cell Proteom."},{"key":"B40","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1016\/j.ajhg.2018.01.020","article-title":"Biallelic mutations in ATP5F1D, which encodes a subunit of ATP synthase, cause a metabolic disorder.","volume":"102","author":"Ol\u00e1hov\u00e1","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"B41","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/jnc.12317","article-title":"Clinical features of Friedreich\u2019s ataxia: Classical and atypical phenotypes.","volume":"126","author":"Parkinson","year":"2013","journal-title":"J. Neurochem."},{"key":"B42","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1093\/EMBOJ\/21.3.221","article-title":"The ATP synthase is involved in generating mitochondrial cristae morphology.","volume":"21","author":"Paumard","year":"2002","journal-title":"EMBO J."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/J.MOLMET.2022.101456","article-title":"Skeletal muscle undergoes fiber type metabolic switch without myosin heavy chain switch in response to defective fatty acid oxidation.","volume":"59","author":"Pereyra","year":"2022","journal-title":"Mol. Metab."},{"key":"B44","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1038\/s41586-020-2290-0","article-title":"Structural basis for catalysis and substrate specificity of human ACAT1.","volume":"581","author":"Qian","year":"2020","journal-title":"Nature"},{"key":"B45","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1038\/NG1097-215","article-title":"Aconitase and mitochondrial iron-sulphur protein deficiency in friedreich ataxia.","volume":"17","author":"Rotig","year":"1997","journal-title":"Nat. Genet."},{"key":"B46","doi-asserted-by":"publisher","first-page":"3688","DOI":"10.1111\/FEBS.14502","article-title":"Muscle fiber type diversity revealed by anti-myosin heavy chain antibodies.","volume":"285","author":"Schiaffino","year":"2018","journal-title":"FEBS J."},{"key":"B47","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1111\/SMS.12606","article-title":"Mitochondrial specialization revealed by single muscle fiber proteomics: Focus on the Krebs cycle.","volume":"25","author":"Schiaffino","year":"","journal-title":"Scand. J. Med. Sci. Sports"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1186\/S13395-015-0046-6\/FIGURES\/1","article-title":"Developmental myosins: Expression patterns and functional significance.","volume":"5","author":"Schiaffino","year":"","journal-title":"Skelet Muscle"},{"key":"B49","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1093\/HMG\/DDM038","article-title":"Mitochondrial frataxin interacts with ISD11 of the NFS1\/ISCU complex and multiple mitochondrial chaperones.","volume":"16","author":"Shan","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/J.MITO.2015.08.003","article-title":"Investigation of mitochondrial DNA variations among Indian Friedreich\u2019s ataxia (FRDA) patients.","volume":"25","author":"Singh","year":"2015","journal-title":"Mitochondrion"},{"key":"B51","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1111\/J.1469-8749.2011.03931.X","article-title":"In children with Friedreich ataxia, muscle and ataxia parameters are associated.","volume":"53","author":"Sival","year":"2011","journal-title":"Dev. Med. Child. Neurol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"D447","DOI":"10.1093\/NAR\/GKU1003","article-title":"STRING v10: Protein\u2013protein interaction networks, integrated over the tree of life.","volume":"43","author":"Szklarczyk","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2022.109828","article-title":"Friedreich\u2019s ataxia related diabetes: Epidemiology and management practices.","volume":"186","author":"Tamaroff","year":"2022","journal-title":"Diabetes Res. Clin. Pract."},{"key":"B54","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1016\/J.BBADIS.2018.01.010","article-title":"Quantitative proteomics in Friedreich\u2019s ataxia B-lymphocytes: A valuable approach to decipher the biochemical events responsible for pathogenesis.","volume":"1864","author":"T\u00e9lot","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"B55","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1042\/BJ20101116","article-title":"The Friedreich\u2019s ataxia protein frataxin modulates DNA base excision repair in prokaryotes and mammals.","volume":"432","author":"Thierbach","year":"2010","journal-title":"Biochem. J."},{"key":"B56","doi-asserted-by":"publisher","first-page":"26994","DOI":"10.1074\/JBC.M203189200","article-title":"Structural and functional genomics of the CPT1B gene for muscle-type carnitine palmitoyltransferase I in mammals.","volume":"277","author":"Van Der Leij","year":"2002","journal-title":"J. Biol. Chem."},{"key":"B57","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1111\/JNC.12215","article-title":"Prevalence gradients of Friedreich\u2019s ataxia and R1b haplotype in Europe co-localize, suggesting a common Palaeolithic origin in the Franco-Cantabrian ice age refuge.","volume":"126","author":"Vankan","year":"2013","journal-title":"J. Neurochem."},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1172\/JCI.INSIGHT.155201","article-title":"Frataxin deficiency lowers lean mass and triggers the integrated stress response in skeletal muscle.","volume":"7","author":"V\u00e1squez-Trincado","year":"2022","journal-title":"JCI Insight"},{"key":"B59","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1016\/S0960-8966(00)00108-5","article-title":"Mitochondrial impairment of human muscle in Friedreich ataxia in vivo.","volume":"10","author":"Vorgerd","year":"2000","journal-title":"Neuromuscul. Disord."},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1113\/JPHYSIOL.2013.268177","article-title":"Deficiency of slow skeletal muscle troponin T causes atrophy of type I slow fibres and decreases tolerance to fatigue.","volume":"592","author":"Wei","year":"2014","journal-title":"J. Physiol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1016\/j.isci.2019.08.056","article-title":"Structural basis of mitochondrial scaffolds by prohibitin complexes: Insight into a role of the coiled-coil region.","volume":"19","author":"Yoshinaka","year":"2019","journal-title":"iScience"}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2023.1289027\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T10:44:20Z","timestamp":1698749060000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2023.1289027\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,31]]},"references-count":61,"alternative-id":["10.3389\/fnins.2023.1289027"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2023.1289027","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,31]]},"article-number":"1289027"}}