Emergent visual creativity in frontotemporal dementia is associated with dorsomedial visual cortex enhancement

IMPORTANCE The neurological substrates of visual creativity are unknown. We demonstrate the role of dorsomedial visual cortex in emergence of visual artistic creativity (VAC) in the setting of dementia. Our findings illuminate neural substrates of human creativity and suggest that hyperactivation of specific brain areas may manifest as enhanced cognitive or behavioral capacities. OBJECTIVE To determine the anatomical and physiological underpinnings of VAC in dementia. DESIGN, SETTING, AND PARTICIPANTS As part of a prospective, longitudinal cohort study focused on frontotemporal dementia (FTD), 734 patients met research criteria for an FTD spectrum disorder between 2002 and 2019. Of these, seventeen showed emergence of visual artistic creativity (VAC-FTD). Two control groups (n = 51 each) were matched to VAC-FTD based on demographic and clinical parameters: (1) Not Visually Artistic FTD (NVA-FTD) and (2) Healthy Controls (HC). MAIN OUTCOMES AND MEASURES Clinical, neuropsychological, genetic and neuroimaging data were analyzed to characterize VAC-FTD and compare VAC-FTD to control groups. RESULTS Emergence of VAC occurred around the time of onset of symptoms, and was disproportionately seen in patients with temporal lobe predominant degeneration (n = 8/17). Atrophy network mapping identified a dorsomedial occipital region whose activity inversely correlated, in healthy brains, with activity in the patient-specific atrophy patterns in VAC-FTD (n = 17/17) and NVA-FTD (n = 45/51). Structural covariance analysis revealed that volume of this dorsal occipital region was strongly correlated, in VAC-FTD, but not in NVA-FTD or HC, with a volume in the primary motor cortex corresponding to the right hand representation. One patient, who underwent fluorodeoxyglucose positron emission tomography before and after VAC onset, showed increasing glucose metabolism in the dorsal occipital region over the interval when creativity emerged. CONCLUSIONS AND RELEVANCE FTD lesion-induced intensification of dorsal visual association cortex structure and function predisposes to emergence of VAC in certain environmental or genetic conditions. Paradoxical gains of function are early manifestations of neurodegenerative disease, and this study delineates a specific brain region associated with the emergence of VAC. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by NIH grants P01AG019724, P30AG062422, grant 2021-A-023-FEL from the Larry L. Hillblom Foundation (Dr Friedberg), the Global Brain Health Institute, Alzheimers Association, and Alzheimers Society Pilot Awards for Global Brain Health Leaders GBHI ALZ UK-21-721419 (Dr Friedberg), NIH grant K99AG065457 (Dr Pasquini), GBHI ALZ UK-21-720973 (Dr Illan-Gala), AACSF-21-850193 (Dr Illan-Gala), the Juan Rodes Contract JR20/0018 (Dr Illan-Gala) ,"Fondo de Investigaciones Sanitario" from Instituto de Salud Carlos III PI21/00791 (Dr Illan-Gala), NIH grant K99AG065501 (Dr La Jioe), NIH grant R01AG062588 (Dr Yokoyama) the Rainwater Foundation (Dr Yokoyama), NIH grant K23AG048291 (Dr ZA Miller), NIH grant K24AG053435 (Dr Grinberg), NIH grant R01NS050915 (Dr Gorno-Tempini), K24DC015544 (Dr Gorno-Tempini), the Charles and Helen Schwab Foundation (Dr Gorno-Tempini) Samples from the National Cell Repository for Alzheimer's Disease (NCRAD), which receives government support under a cooperative agreement grant (U24AG021886) awarded by the National Institute on Aging (NIA), were used in this study. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All participants provided written informed consent, and the University of California, San Francisco, Committee on Human Research approved the study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors