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However, the phenotypic repertoire and neuroanatomical substrates of abnormal reward behaviour in these diseases remain incompletely characterized and poorly understood. Here we addressed these issues in a large, intensively phenotyped patient cohort representing all major syndromes of sporadic frontotemporal dementia and Alzheimer\u2019s disease. We studied 27 patients with behavioural variant frontotemporal dementia, 58 with primary progressive aphasia (22 semantic variant, 24 non-fluent\/agrammatic variant and 12 logopenic) and 34 with typical amnestic Alzheimer\u2019s disease, in relation to 42 healthy older individuals. Changes in behavioural responsiveness were assessed for canonical primary rewards (appetite, sweet tooth, sexual activity) and non-primary rewards (music, religion, art, colours), using a semi-structured survey completed by patients\u2019 primary caregivers. Changes in more general socio-emotional behaviours were also recorded. We applied multiple correspondence analysis and k-means clustering to map relationships between hedonic domains and extract core factors defining aberrant hedonic phenotypes. Neuroanatomical associations were assessed using voxel-based morphometry of brain MRI images across the combined patient cohort. Altered (increased and\/or decreased) reward responsiveness was exhibited by most patients in the behavioural and semantic variants of frontotemporal dementia and around two-thirds of patients in other dementia groups, significantly (P &amp;lt; 0.05) more frequently than in healthy controls. While food-directed changes were most prevalent across the patient cohort, behavioural changes directed toward non-primary rewards occurred significantly more frequently (P &amp;lt; 0.05) in the behavioural and semantic variants of frontotemporal dementia than in other patient groups. Hedonic behavioural changes across the patient cohort were underpinned by two principal factors: a \u2018gating\u2019 factor determining the emergence of altered reward behaviour and a \u2018modulatory\u2019 factor determining how that behaviour is directed. These factors were expressed jointly in a set of four core, trans-diagnostic and multimodal hedonic phenotypes: \u2018reward-seeking\u2019, \u2018reward-restricted\u2019, \u2018eating-predominant\u2019 and \u2018control-like\u2019\u2014variably represented across the cohort and associated with more pervasive socio-emotional behavioural abnormalities. The principal gating factor was associated (P &amp;lt; 0.05 after correction for multiple voxel-wise comparisons over the whole brain) with a common profile of grey matter atrophy in anterior cingulate, bilateral temporal poles, right middle frontal and fusiform gyri: the cortical circuitry that mediates behavioural salience and semantic and affective appraisal of sensory stimuli. Our findings define a multi-domain phenotypic architecture for aberrant reward behaviours in major dementias, with novel implications for the neurobiological understanding and clinical management of these diseases.<\/jats:p>","DOI":"10.1093\/braincomms\/fcad027","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T00:01:32Z","timestamp":1675814492000},"source":"Crossref","is-referenced-by-count":28,"title":["The architecture of abnormal reward behaviour in dementia: multimodal hedonic phenotypes and brain substrate"],"prefix":"10.1093","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7973-8267","authenticated-orcid":false,"given":"Anthipa","family":"Chokesuwattanaskul","sequence":"first","affiliation":[{"name":"Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London , London , UK"},{"name":"Division of Neurology, Department of Internal Medicine, King Chulalongkorn Memorial Hospital, Thai Red Cross Society , Bangkok , Thailand"},{"name":"Cognitive Clinical and Computational Neuroscience Research Unit, Faculty of Medicine, Chulalongkorn University , Bangkok , Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harmony","family":"Jiang","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca L","family":"Bond","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A","family":"Jimenez","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London , London , UK"},{"name":"Department of Neurological Sciences, Faculty of Medicine, University of Chile , Santiago , Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy L","family":"Russell","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harri","family":"Sivasathiaseelan","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy C S","family":"Johnson","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elia","family":"Benhamou","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L","family":"Agustus","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janneke E P","family":"van Leeuwen","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peerapat","family":"Chokesuwattanaskul","sequence":"additional","affiliation":[{"name":"Faculty of Law, Chulalongkorn University , Bangkok , Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris J D","family":"Hardy","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles R","family":"Marshall","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London , London , UK"},{"name":"Preventive Neurology Unit, Wolfson Institute of Population Health, Queen Mary University of London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D","family":"Rohrer","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason D","family":"Warren","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,2,9]]},"reference":[{"issue":"3","key":"2023031804553843000_","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1152\/physrev.00023.2014","article-title":"Neuronal reward and decision signals: From theories to data","volume":"95","author":"Schultz","year":"2015","journal-title":"Physiol 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