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Although insufficiently investigated, their distinction holds important clinical relevance for accurate diagnosis of ALS with behavioural impairment and for patients\u2019 prognosis and management. In the present study, we aimed to assess both apathy and depressive symptoms in patients with ALS and whether they have similar or different functional neural correlates.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Using graph analysis and connectomics, global and lobar nodal properties and regional functional brain connectivity were assessed in ALS patients without apathy\/depression (ALSn, <jats:italic>n<\/jats:italic>\u2009=\u200942), with apathy without depression (ALSa, <jats:italic>n<\/jats:italic>\u2009=\u200914), with depressive symptoms without apathy (ALSd, <jats:italic>n<\/jats:italic>\u2009=\u200920), and with apathy and depressive symptoms (ALSad, <jats:italic>n<\/jats:italic>\u2009=\u20096), and 46 healthy controls. Correlations between brain functional properties, apathy and depressive symptoms were performed in all patients.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Depressive symptoms were related with reduced path length within bilateral basal ganglia (BG) network, and apathy was related with increased path length, decreased nodal strength and local efficiency within left BG network. ALSa patients showed altered functional nodal properties within BG network compared to ALSn and ALSd. Compared to healthy controls and all non-apathetic patients (ALSn and ALSd), all apathetic patients (ALSa and ALSad) exhibited altered functional nodal properties within parietal, occipital and frontal networks. Non-apathetic patients, compared to apathetic patients, showed relatively preserved functional nodal properties in the BG network.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our findings indicate differences in brain functional neural organization associated with apathy and depression, underscoring the importance of distinguishing these symptoms in ALS and highlighting the need for targeted interventions.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00415-025-13247-1","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T19:08:13Z","timestamp":1752520093000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Brain functional connectivity changes in amyotrophic lateral sclerosis with apathy and depression"],"prefix":"10.1007","volume":"272","author":[{"given":"Veronica","family":"Castelnovo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Canu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Basaia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edoardo Gioele","family":"Spinelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabiola","family":"Freri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paride","family":"Schito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tommaso","family":"Russo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuri","family":"Falzone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"Verde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Torre","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Poletti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucio","family":"Tremolizzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ildebrando","family":"Appollonio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Ticozzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Silani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Filippi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3121-4979","authenticated-orcid":false,"given":"Federica","family":"Agosta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,7,14]]},"reference":[{"key":"13247_CR1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.620198","volume":"12","author":"S Benbrika","year":"2021","unstructured":"Benbrika S, Doidy F, Carluer L, Mondou A, Pelerin A, Eustache F, Viader F, Desgranges B (2021) Longitudinal study of cognitive and emotional alterations in amyotrophic lateral sclerosis: clinical and imaging data. 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Castelnovo has nothing to disclose; E. Canu has received research supports from the Italian Ministry of Health; S. Basaia, E.G. Spinelli, F. Freri, P. Schito, T. Russo, Y. Falzone have nothing to disclose; F. Verde is Associate Editor for Journal of Alzheimer\u2019s Disease; S. Torre has nothing to disclose; B. Poletti received compensation for consulting services and\/or speaking activities from Liquidweb S.r.l. She is Associate Editor for Frontiers in Neuroscience; L. Tremolizzo, I. Appollonio, N. Ticozzi have nothing to disclose; V. Silani received compensation for consulting services and\/or speaking activities from AveXis, Cytokinetics, Italfarmaco, Liquidweb S.r.l., Novartis Pharma AG, Amylyx Pharmaceuticals, Biogen, and Zambon Biotech SA; he receives or has received research supports from the Italian Ministry of Health, AriSLA, and E-Rare Joint Transnational Call; he is in the Editorial Board of Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, European Neurology, American Journal of Neurodegenerative Diseases, Frontiers in Neurology, and Exploration of Neuroprotective Therapy; M. Filippi is Editor-in-Chief of the Journal of Neurology, Associate Editor of Human Brain Mapping, Neurological Sciences, and Radiology, received compensation for consulting services from Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi, speaking activities from Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA, participation in Advisory Boards for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda, scientific direction of educational events for Biogen, Merck, Roche, Celgene, Bristol-Myers Squibb, Lilly, Novartis, Sanofi-Genzyme, he receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla; F. Agosta is Associate Editor of NeuroImage: Clinical, has received speaker honoraria from Biogen Idec, Roche, Eli Lilly and GE Healthcare, and receives or has received research supports from the Italian Ministry of Health, the Italian Ministry of University and Research, AriSLA (Fondazione Italiana di Ricerca per la SLA), the European Research Council, the EU Joint Programme\u2014Neurodegenerative Disease Research (JPND), and Foundation Research on Alzheimer Disease (France).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"Before participating, all participants provided written informed consent according to the Declaration of Helsinki. The local ethical standards committee on human experimentation approved the study protocol.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"509"}}