Prevalence, Timing, and Network Localization of Emergent Visual Creativity in Frontotemporal Dementia

Abstract

Altres ajuts: National Institutes of Health (NIH - P01AG019724, P30AG062422, K99AG065501, K99AG065457, R01AG062588, K23AG048291, K24AG053435, R01NS050915, K24DC015544); Larry L. Hillblom Foundation (2021-A-023-FEL); Global Brain Health Institute, Alzheimer's Association, and Alzheimer's Society Pilot Awards for Global Brain Health Leaders (GBHI ALZ UK-21-721419, GBHI ALZ UK-21-720973, AACSF-21-850193); Rainwater Foundation; Charles and Helen Schwab Foundation. Samples from the National Cell Repository for Alzheimer's Disease, which receives government support under a cooperative agreement grant (U24AG021886) awarded by the National Institute on Aging, were used in this study.

This case-control study assesses the anatomical and physiological underpinnings of visual artistic creativity in individuals with frontotemporal dementia. What are the neural underpinnings of visual artistic creativity (VAC) in the setting of frontotemporal dementia (FTD)? In this study of 119 patients, VAC occurred early in the course of FTD, was disproportionately observed in patients with temporal lobe-predominant degeneration, and may be associated with damage to brain regions that normally suppress dorsomedial occipital cortex function. This work generated a novel hypothesis about the mechanisms underlying the emergence of VAC in FTD, setting the stage to study in-depth enhanced capacities arising early in the course of neurodegeneration. The neurological substrates of visual artistic creativity (VAC) are unknown. VAC is demonstrated here to occur early in frontotemporal dementia (FTD), and multimodal neuroimaging is used to generate a novel mechanistic hypothesis involving dorsomedial occipital cortex enhancement. These findings may illuminate a novel mechanism underlying human visual creativity. To determine the anatomical and physiological underpinnings of VAC in FTD. This case-control study analyzed records of 689 patients who met research criteria for an FTD spectrum disorder between 2002 and 2019. Individuals with FTD and emergence of visual artistic creativity (VAC-FTD) were matched to 2 control groups based on demographic and clinical parameters: (1) not visually artistic FTD (NVA-FTD) and (2) healthy controls (HC). Analysis took place between September 2019 to December 2021. Clinical, neuropsychological, genetic, and neuroimaging data were analyzed to characterize VAC-FTD and compare VAC-FTD with control groups. Of 689 patients with FTD, 17 (2.5%) met VAC-FTD inclusion criteria (mean [SD] age, 65 [9.7] years; 10 [58.8%] female). NVA-FTD (n = 51; mean [SD] age, 64.8 [7] years; 25 [49.0%] female) and HC (n = 51; mean [SD] age, 64.5 [7.2] years; 25 [49%] female) groups were well matched to VAC-FTD demographically. Emergence of VAC occurred around the time of onset of symptoms and was disproportionately seen in patients with temporal lobe predominant degeneration (8 of 17 [47.1%]). Atrophy network mapping identified a dorsomedial occipital region whose activity inversely correlated, in healthy brains, with activity in regions found within the patient-specific atrophy patterns in VAC-FTD (17 of 17) and NVA-FTD (45 of 51 [88.2%]). Structural covariance analysis revealed that the 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. This study generated a novel hypothesis about the mechanisms underlying the emergence of VAC in FTD. These findings suggest that early lesion-induced activation of dorsal visual association areas may predispose some patients to the emergence of VAC under certain environmental or genetic conditions. This work sets the stage for further exploration of enhanced capacities arising early in the course of neurodegeneration.