{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:01:23Z","timestamp":1772164883541,"version":"3.50.1"},"reference-count":53,"publisher":"MIT Press","license":[{"start":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T00:00:00Z","timestamp":1713830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["direct.mit.edu"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,5,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Aging is associated with impaired signaling between brain regions when measured using resting-state functional magnetic resonance imaging (fMRI). This age-related destabilization and desynchronization of brain networks reverses itself when the brain switches from metabolizing glucose to ketones. Here, we probe the mechanistic basis for these effects. First, we confirmed their robustness across measurement modalities using two datasets acquired from resting-state EEG (Lifespan: standard diet, 20\u201380 years, N = 201; Metabolic: individually weight-dosed and calorically-matched glucose and ketone ester challenge, \u03bcage = 26.9 \u00b111.2 years, N = 36). Then, using a multiscale conductance-based neural mass model, we identified the unique set of mechanistic parameters consistent with our clinical data. Together, our results implicate potassium (K+) gradient dysregulation as a mechanism for age-related neural desynchronization and its reversal with ketosis, the latter finding of which is consistent with direct measurement of ion channels. As such, the approach facilitates the connection between macroscopic brain activity and cellular-level mechanisms.<\/jats:p>","DOI":"10.1162\/imag_a_00163","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T19:06:54Z","timestamp":1713899214000},"update-policy":"https:\/\/doi.org\/10.1162\/mitpressjournals.corrections.policy","source":"Crossref","is-referenced-by-count":3,"title":["Ketosis regulates K+ ion channels, strengthening brain-wide signaling disrupted by age"],"prefix":"10.1162","volume":"2","author":[{"given":"Helena","family":"van Nieuwenhuizen","sequence":"first","affiliation":[{"name":"Department of Physics and Astronomy, Stony Brook University, Stony Brook, NY, United States"},{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony G.","family":"Chesebro","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States"},{"name":"Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, United States"},{"name":"Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Polizu","sequence":"additional","affiliation":[{"name":"Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kieran","family":"Clarke","sequence":"additional","affiliation":[{"name":"Department of Physiology, Oxford University, Oxford, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helmut H.","family":"Strey","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, United States"},{"name":"Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, NY, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corey","family":"Weistuch","sequence":"additional","affiliation":[{"name":"Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lilianne R.","family":"Mujica-Parodi","sequence":"additional","affiliation":[{"name":"Department of Physics and Astronomy, Stony Brook University, Stony Brook, NY, United States"},{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States"},{"name":"Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, United States"},{"name":"Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, NY, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"281","published-online":{"date-parts":[[2024,5,8]]},"reference":[{"issue":"10","key":"2025081116464707900_b1","doi-asserted-by":"crossref","first-page":"160201","DOI":"10.1098\/rsos.160201","article-title":"Global field synchronization reveals rapid eye movement sleep as most synchronized brain state in the human EEG","volume":"3","author":"Achermann","year":"2016","journal-title":"Royal Society Open Science"},{"key":"2025081116464707900_b2","doi-asserted-by":"crossref","first-page":"e73138","DOI":"10.7554\/eLife.73138","article-title":"Type 2 diabetes mellitus accelerates brain aging and cognitive decline: Complementary findings from UK Biobank and meta-analyses","volume":"11","author":"Antal","year":"2022","journal-title":"Elife"},{"issue":"1","key":"2025081116464707900_b3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/sdata.2018.308","article-title":"A mind-brain-body dataset of MRI, EEG, cognition, emotion, and peripheral physiology in young and old adults","volume":"6","author":"Babayan","year":"2019","journal-title":"Scientific Data"},{"issue":"3","key":"2025081116464707900_b4","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.cmet.2018.11.005","article-title":"Non-canonical control of neuronal energy status by the Na+ pump","volume":"29","author":"Baeza-Lehnert","year":"2019","journal-title":"Cell Metabolism"},{"issue":"1","key":"2025081116464707900_b5","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1001\/archneurol.2010.225","article-title":"Insulin resistance and Alzheimer-like reductions in regional cerebral glucose metabolism for cognitively normal adults with prediabetes or early type 2 diabetes","volume":"68","author":"Baker","year":"2011","journal-title":"Archives of Neurology"},{"issue":"6","key":"2025081116464707900_b6","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1007\/s11940-008-0043-8","article-title":"The ketogenic diet: Uses in epilepsy and other neurologic illnesses","volume":"10","author":"Bara\u00f1ano","year":"2008","journal-title":"Current Treatment Options in Neurology"},{"issue":"10","key":"2025081116464707900_b7","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1212\/01.WNL.0000144278.79488.DD","article-title":"Diabetes mellitus in midlife and the risk of dementia three decades later","volume":"63","author":"Beeri","year":"2004","journal-title":"Neurology"},{"issue":"4","key":"2025081116464707900_b8","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1088\/0954-898X_14_4_305","article-title":"Modulation of excitatory synaptic coupling facilitates synchronization and complex dynamics in a biophysical model of neuronal dynamics","volume":"14","author":"Breakspear","year":"2003","journal-title":"Network: Computation in Neural Systems"},{"issue":"2","key":"2025081116464707900_b9","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1152\/jn.00406.2019","article-title":"Next-generation neural mass and field modeling","volume":"123","author":"Byrne","year":"2020","journal-title":"Journal of Neurophysiology"},{"key":"2025081116464707900_b10","doi-asserted-by":"crossref","first-page":"106207","DOI":"10.1016\/j.nbd.2023.106207","article-title":"Lactate as a determinant of neuronal excitability, neuroenergetics and beyond","volume":"184","author":"Cauli","year":"2023","journal-title":"Neurobiology of Disease"},{"key":"2025081116464707900_b11","doi-asserted-by":"crossref","first-page":"113120","DOI":"10.1016\/j.chaos.2023.113120","article-title":"Ion gradient-driven bifurcations of a multi-scale neuronal model","volume":"167","author":"Chesebro","year":"2023","journal-title":"Chaos, Solitons & Fractals"},{"issue":"1","key":"2025081116464707900_b12","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/nyas.12999","article-title":"Can ketones compensate for deteriorating brain glucose uptake during aging? 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