{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:11:14Z","timestamp":1777396274562,"version":"3.51.4"},"reference-count":96,"publisher":"SAGE Publications","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2022,12,6]]},"abstract":"<jats:p>Background: Earlier studies have described the neural markers of apathy in Alzheimer\u2019s disease (AD) and mild cognitive impairment (MCI), but few focused on the motivation circuits. Here, we targeted hypothalamus, a hub of the motivation circuit. Objective: To examine hypothalamic resting state functional connectivity (rsFC) in relation to apathy. Methods: We performed whole-brain regression of hypothalamic rsFC against Apathy Evaluation Scale (AES) total score and behavioral, cognitive, and emotional subscores in 29 patients with AD\/MCI and 28 healthy controls (HC), controlling for age, sex, education, cognitive status, and depression. We evaluated the results at a corrected threshold and employed path analyses to assess possible interaction between hypothalamic rsFCs, apathy and depression\/memory. Finally, we re-examined the findings in a subsample of amyloid-\u03b2-verified AD. Results: AES total score correlated negatively with hypothalamic precuneus (PCu)\/posterior cingulate cortex (PCC) and positively with left middle temporal gyrus (MTG) and supramarginal gyrus rsFCs. Behavioral subscore correlated negatively with hypothalamic PCu\/PCC and positively with middle frontal gyrus rsFC. Cognitive subscore correlated positively with hypothalamic MTG rsFC. Emotional subscore correlated negatively with hypothalamic calcarine cortex rsFC. In path analyses, hypothalamic-PCu\/PCC rsFC negatively modulated apathy and, in turn, depression. The model where hypothalamic MTG rsFC and memory independently modulated apathy also showed a good fit. The findings of diminished hypothalamic-PCu\/PCC rsFC in relation to apathy and, in turn, depression were confirmed in amyloid-verified AD. Conclusion: The findings together support a role of altered hypothalamic connectivity in relation to apathy and depression, and modulation of apathy by memory dysfunction.<\/jats:p>","DOI":"10.3233\/jad-220708","type":"journal-article","created":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T11:45:28Z","timestamp":1666698328000},"page":"1615-1628","source":"Crossref","is-referenced-by-count":16,"title":["Hypothalamic Functional Connectivity and Apathy in People with Alzheimer\u2019s Disease and Cognitively Normal Healthy Controls"],"prefix":"10.1177","volume":"90","author":[{"given":"Shefali","family":"Chaudhary","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Zhornitsky","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herta H.","family":"Chao","sequence":"additional","affiliation":[{"name":"VA Connecticut Healthcare System, West Haven, CT, USA"},{"name":"Department of Medicine & Yale Comprehensive Cancer Center, Yale University School of Medicine, New Haven, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher H.","family":"van Dyck","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA"},{"name":"Alzheimer\u2019s Disease Research Unit, Yale University School of Medicine, New Haven, CT, USA"},{"name":"Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA"},{"name":"Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiang-Shan R.","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA"},{"name":"Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA"},{"name":"Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT, USA"},{"name":"Wu Tsai Institute, Yale University, New Haven, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-220708_ref1","first-page":"119","article-title":"Apathy as a treatment target in Alzheimer\u2019sdisease: Implications for clinical trials","volume":"30","author":"Mortby","year":"2022","journal-title":"Am J GeriatrPsychiatry"},{"key":"10.3233\/JAD-220708_ref2","first-page":"7","article-title":"Apathy in Alzheimer\u2019s disease","volume":"22","author":"Nobis","year":"2018","journal-title":"CurrOpin Behav 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Extra"},{"key":"10.3233\/JAD-220708_ref6","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1097\/JGP.0b013e31818a0e35","article-title":"Apathy predicts more severe parkinsonism in Alzheimer\u2019sdisease","volume":"17","author":"Starkstein","year":"2009","journal-title":"Am J Geriatr Psychiatry"},{"key":"10.3233\/JAD-220708_ref7","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jagp.2020.04.026","article-title":"Neurobiologic rationale fortreatment of apathy in Alzheimer\u2019s disease with methylphenidate","volume":"29","author":"van Dyck","year":"2021","journal-title":"Am J Geriatr Psychiatry"},{"key":"10.3233\/JAD-220708_ref8","doi-asserted-by":"crossref","first-page":"10996","DOI":"10.1523\/JNEUROSCI.22-24-10996.2002","article-title":"The role of rat medial frontal cortex in effort-based decision making","volume":"22","author":"Walton","year":"2002","journal-title":"J Neurosci"},{"key":"10.3233\/JAD-220708_ref9","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.3233\/JAD-215316","article-title":"Cerebral volumetric correlates of apathy in Alzheimer\u2019s disease andcognitively normal older adults: Meta-analysis, label-based review,and study of an independent cohort.","volume":"85","author":"Chaudhary","year":"2022","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-220708_ref10","first-page":"1388","article-title":"Afunctional magnetic resonance imaging study of amygdala responses tohuman faces in aging and mild Alzheimer\u2019s disease","volume":"62","author":"Wright","year":"2007","journal-title":"BiolPsychiatry"},{"key":"10.3233\/JAD-220708_ref11","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1176\/appi.neuropsych.12110261","article-title":"Functional magneticresonance imaging study of apathy in Alzheimer\u2019s disease","volume":"26","author":"Zhao","year":"2014","journal-title":"JNeuropsychiatry Clin Neurosci"},{"key":"10.3233\/JAD-220708_ref13","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1093\/brain\/awz026","article-title":"Functional connectivity associated with tau levels in ageing,Alzheimer\u2019s, and small vessel disease","volume":"142","author":"Franzmeier","year":"2019","journal-title":"Brain"},{"key":"10.3233\/JAD-220708_ref14","doi-asserted-by":"crossref","first-page":"4678","DOI":"10.1093\/cercor\/bhu151","article-title":"Disrupted intrinsicnetworks link amyloid-\u03b2 pathology and impaired cognition inprodromal Alzheimer\u2019s disease","volume":"25","author":"Koch","year":"2015","journal-title":"Cereb Cortex"},{"key":"10.3233\/JAD-220708_ref15","doi-asserted-by":"crossref","first-page":"363","DOI":"10.5152\/dir.2019.19445","article-title":"Resting-state fMRIanalysis in apathetic Alzheimer\u2019s disease","volume":"26","author":"B\u00fcy\u00fckg\u00f6k","year":"2020","journal-title":"Diagn 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criteria","volume":"31","author":"Benoit","year":"2012","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-220708_ref45","first-page":"21","article-title":"Apathy and depression:Which clinical specificities?-}","volume":"8","author":"Batail","year":"2018","journal-title":"Pers Med Psychiatry"},{"key":"10.3233\/JAD-220708_ref46","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.jalz.2011.03.005","article-title":"The diagnosis of dementia due to Alzheimer\u2019s disease:Recommendations from the National Institute on Aging-Alzheimer\u2019sAssociation workgroups on diagnostic guidelines for Alzheimer\u2019sdisease","volume":"7","author":"McKhann","year":"2011","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-220708_ref47","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13195-020-00742-y","article-title":"Association of A\u03b2 deposition and regionalsynaptic density in early Alzheimer\u2019s disease: A PET imaging studywith [(11)C]UCB-J","volume":"13","author":"O\u2019Dell","year":"2021","journal-title":"Alzheimers Res Ther"},{"key":"10.3233\/JAD-220708_ref48","first-page":"270","article-title":"The diagnosis of mild cognitiveimpairment due to Alzheimer\u2019s disease: Recommendations from theNational Institute on Aging-Alzheimer\u2019s Association workgroups ondiagnostic guidelines for Alzheimer\u2019s disease","volume":"7","author":"Albert","year":"2011","journal-title":"AlzheimersDement"},{"key":"10.3233\/JAD-220708_ref49","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/0165-1781(91)90040-V","article-title":"Reliability and validity of the Apathy Evaluation Scale","volume":"38","author":"Marin","year":"1991","journal-title":"Psychiatry Res"},{"key":"10.3233\/JAD-220708_ref50","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.jns.2014.10.027","article-title":"Apathy in multiple sclerosis: A validation study of the apathy evaluation 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imaging","volume":"8","author":"Fox","year":"2007","journal-title":"Nat Rev Neurosci"},{"key":"10.3233\/JAD-220708_ref61","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.1016\/j.neuroimage.2011.10.018","article-title":"Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion","volume":"59","author":"Power","year":"2012","journal-title":"Neuroimage"},{"key":"10.3233\/JAD-220708_ref62","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.neuroimage.2019.04.016","article-title":"Global signal regressionstrengthens association between resting-state functionalconnectivity and behavior","volume":"196","author":"Li","year":"2019","journal-title":"Neuroimage"},{"key":"10.3233\/JAD-220708_ref63","first-page":"1326","article-title":"Frequencies contributing to functional connectivity in the cerebral cortex in \u201cresting-state\u201d data","volume":"22","author":"Cordes","year":"2001","journal-title":"AJNR Am J 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