{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T06:09:26Z","timestamp":1775628566839,"version":"3.50.1"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cognitive impairment persists during partial or full remission in 50\u201370% of individuals with mood disorders and impacts daily functioning and clinical prognosis. Preclinical evidence suggests that extended exposure to moderate hypoxia, combined with motor-cognitive learning, may elevate neuroplasticity and improve cognition. In these individuals with remitted mood disorders, we found that cognitive training under repeated moderate normobaric hypoxia improved executive function, and here investigate neurobiological mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Participants with major depressive disorder (MDD) or bipolar disorder (BD) in partial or full remission were randomized to 3\u202fweeks of 3.5-h daily normobaric hypoxia (12% O\n                      <jats:sub>2<\/jats:sub>\n                      ) combined with cognitive training five to 6\u202fdays per week or treatment-as-usual (TAU). Participants were assessed with cognitive tests and diffusion-weighted MRI at baseline and 1\u202fmonth after treatment completion (week 8) as part of the ALTIBRAIN trial (\n                      <jats:uri>ClinicalTrials.gov<\/jats:uri>\n                      : NCT06121206). Prefrontal and hippocampal gray matter microstructure were modelled with Neurite Orientation Dispersion and Density Imaging (NODDI).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fifty-seven participants (mean age 39\u202fyears, SD: 13, 70% female) with baseline MRI data were included. No significant effects of hypoxia-cognition training vs. TAU on neurite density index (NDI) or orientation dispersion index (ODI) were observed in either the prefrontal cortex or hippocampus (all p-FDR\u202f\u2265\u202f0.832). No significant associations were observed between microstructural changes and changes in cognitive function in either region (all p-FDR\u202f\u2265\u202f0.721). At baseline, microstructure in both regions was not associated with executive function or global cognition (all\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;gt;\u202f0.40).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The absence of detectable microstructural changes, despite selective improvements in executive function, indicates that NODDI-derived metrics did not capture structural correlates of the cognitive response to hypoxia-cognition training. Whether this reflects functional neural mechanisms, measurement insensitivity, or the timing of the single follow-up assessment remains to be determined. Future studies should incorporate multiple imaging time points to capture the dynamic trajectories of putative microstructural brain changes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnins.2026.1798024","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T05:32:32Z","timestamp":1775626352000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Prefrontal and hippocampal microstructural gray matter following cognitive training under moderate hypoxia in mood disorders: a randomized controlled trial"],"prefix":"10.3389","volume":"20","author":[{"given":"Kristian H. R.","family":"Jensen","sequence":"first","affiliation":[{"name":"Neurobiology Research Unit, Rigshospitalet","place":["Copenhagen, Denmark"]},{"name":"Copenhagen Affective Disorders Research Center (CADIC), Mental Health Center Copenhagen","place":["Copenhagen, Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ida P.","family":"\u00d8stergaard","sequence":"additional","affiliation":[{"name":"The Neurocognition and Emotion Across Disorders of the Brain (NEAD) Centre, Psychiatric Centre Copenhagen","place":["Copenhagen, Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viktoria","family":"Damgaard","sequence":"additional","affiliation":[{"name":"The Neurocognition and Emotion Across Disorders of the Brain (NEAD) Centre, Psychiatric Centre Copenhagen","place":["Copenhagen, Denmark"]},{"name":"Department of Psychology, University of Copenhagen","place":["Copenhagen, Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna M.","family":"Schandorff","sequence":"additional","affiliation":[{"name":"The Neurocognition and Emotion Across Disorders of the Brain (NEAD) Centre, Psychiatric Centre Copenhagen","place":["Copenhagen, Denmark"]},{"name":"Department of Psychology, University of Copenhagen","place":["Copenhagen, Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian","family":"Macoveanu","sequence":"additional","affiliation":[{"name":"The Neurocognition and Emotion Across Disorders of the Brain (NEAD) Centre, Psychiatric Centre Copenhagen","place":["Copenhagen, Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cyril","family":"Pernet","sequence":"additional","affiliation":[{"name":"Neurobiology Research Unit, Rigshospitalet","place":["Copenhagen, Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah W.","family":"Julsgart","sequence":"additional","affiliation":[{"name":"Neurobiology Research Unit, Rigshospitalet","place":["Copenhagen, Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annette","family":"Johansen","sequence":"additional","affiliation":[{"name":"Neurobiology Research Unit, Rigshospitalet","place":["Copenhagen, Denmark"]},{"name":"Department of Neurology, Copenhagen University Hospital, Rigshospitalet","place":["Copenhagen, Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristoffer","family":"Brendstrup-Brix","sequence":"additional","affiliation":[{"name":"Neurobiology Research Unit, Rigshospitalet","place":["Copenhagen, Denmark"]},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen","place":["Copenhagen, Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars V.","family":"Kessing","sequence":"additional","affiliation":[{"name":"Copenhagen Affective Disorders Research Center (CADIC), Mental Health Center Copenhagen","place":["Copenhagen, Denmark"]},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen","place":["Copenhagen, Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin B.","family":"J\u00f8rgensen","sequence":"additional","affiliation":[{"name":"Copenhagen Affective Disorders Research Center (CADIC), Mental Health Center Copenhagen","place":["Copenhagen, Denmark"]},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen","place":["Copenhagen, Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannelore","family":"Ehrenreich","sequence":"additional","affiliation":[{"name":"Experimental Medicine, Central Institute of Mental Health (CIMH)","place":["Mannheim, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gitte M.","family":"Knudsen","sequence":"additional","affiliation":[{"name":"Neurobiology Research Unit, Rigshospitalet","place":["Copenhagen, Denmark"]},{"name":"Department of Neurology, Copenhagen University Hospital, Rigshospitalet","place":["Copenhagen, Denmark"]},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen","place":["Copenhagen, Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamilla","family":"Miskowiak","sequence":"additional","affiliation":[{"name":"Copenhagen Affective Disorders Research Center (CADIC), Mental Health Center Copenhagen","place":["Copenhagen, Denmark"]},{"name":"The Neurocognition and Emotion Across Disorders of the Brain (NEAD) Centre, Psychiatric Centre Copenhagen","place":["Copenhagen, Denmark"]},{"name":"Department of Psychology, University of Copenhagen","place":["Copenhagen, Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"S220\u2013S221","DOI":"10.1192\/j.eurpsy.2022.574","article-title":"Neurotrophics correlates and functional remediation in bipolar disorder. 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