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

Abstract

Importance: 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.

Objective: To determine the anatomical and physiological underpinnings of VAC in FTD.

Design, setting, and participants: 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.

Main outcomes and measures: Clinical, neuropsychological, genetic, and neuroimaging data were analyzed to characterize VAC-FTD and compare VAC-FTD with control groups.

Results: 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.

Conclusions and relevance: 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.

Figure 1.. Clinical Characteristics and Artistic Expression in Patients With Frontotemporal Dementia (FTD) Who Reported Emergence of Visual Artistic Creativity (VAC) (n = 17)

A, Semantic variant of primary progressive aphasia (svPPA) was the most common clinical syndrome in the VAC-FTD group. B, SvPPA was also the FTD syndrome with the highest percentage of patients with VAC relative to the overall syndrome-based cohort, significantly higher than in behavioral variant of frontotemporal dementia (bvFTD) and corticobasal syndrome (CBS) (Fisher exact test, P < .05). C, Painting was the most common modality of visual artistic expression. Painting plus indicates that painting, the primary modality, was accompanied by other forms of visual art: sculpture (n = 1), photography (n = 1), jewelry making, and glass painting (n = 1). D, Most patients showed emergence of visual artistic creativity in close temporal proximity to FTD symptom onset. ALS indicates amyotrophic lateral sclerosis; nfvPPA, nonfluent variant of primary progressive aphasia; PSP-RS, progressive supranuclear palsy with Richardson syndrome. ^aP < .05 for svPPA vs bvFTD and for svPPA vs CBS.

Figure 2.. Examples of the Visual Artworks

Each piece was selected to represent the style of a single patient with a frontotemporal dementia spectrum disease and emergence of visual artistic creativity. Artworks presented were generated by patients with clinical diagnoses of semantic variant of primary progressive aphasia (svPPA) (A and D), behavioral variant of frontotemporal dementia (bvFTD) (B and E), and nonfluent variant of primary progressive aphasia (nfvPPA) (C).

Figure 3.. Atrophy Network Mapping and Structural Covariance Analyses Results

A and B, Individual atrophy network maps were thresholded at t ≥ |7|, binarized, and overlaid to create group-level atrophy network maps. A similar bilateral dorsomedial occipital region showed anticorrelated brain activity, in healthy controls, to the activity seen in the top 1% of atrophied voxels in both individuals with visual artistic creativity with frontotemporal dementia (VAC-FTD) (17 of 17 patients) and patients with a frontotemporal dementia spectrum disease without emergence of visual artistic creativity (NVA-FTD) (45 of 51 patients [88.2%]). C-E, An interaction model, designed to detect brain regions showing greater structural covariance with the dorsomedial occipital region (red) in VAC-FTD vs NVA-FTD, identified a cluster in the right-hand region of the primary motor cortex (green). This cluster was positively correlated with the mean W-score in the occipital region of interest (ROI) in VAC-FTD but showed no correlation in NVA-FTD (D). A similar cluster (blue, panel C) was observed in a second interaction model aimed to identify regions with greater positive correlation in VAC-FTD than in HC (data shown in E). F-H, Distributions of the correlations of the mean W-score of the dorsomedial occipital ROI and the mean W-score of cortical brain regions (parcellated by the Brainnetome atlas) are shown. The VAC-FTD group had significantly stronger positive structural correlations with the ROI. Findings in panels A-C are superimposed on slice and render images of the Montreal Neurological Institute template brain. Images are in neurological orientation (left = left). D and E, The shaded areas represent the 95% CIs for the fitted regression lines. F-H, The vertical black line represents the median.

Figure 4.. Atrophy Network Mapping and Intensified Occipital Glucose Metabolism After Emergence of Visual Artistic Creativity (VAC) in a Patient With Semantic Variant of Primary Progressive Aphasia (svPPA)

A, Top 1% most atrophied voxels from a patient with svPPA and emergent VAC were used as seed to obtain an individual atrophy network map based on the healthy brain connectome. The left anterior temporal lobe regions atrophied in the patient (blue) showed anticorrelated brain activity, in controls, to medial occipital regions (red). B, ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) standardized uptake value ratio (SUVR) maps obtained before and after emergence of VAC show decline in glucose metabolism in temporal and frontal regions bilaterally, accompanied by increasing metabolism in medial occipital regions, right greater than left (arrowhead). C and D, Mean regional FDG-PET W-scores were computed for individual brain regions across the whole brain. For each region, the W-score after VAC onset was subtracted from that obtained prior to VAC onset to generate a corresponding change value for each region. Multiple brain regions, most prominently primary visual and visual association areas and sensorimotor regions, showed increased metabolism after VAC onset, as mapped on a template brain in panel D. Images are in neurological view (left = left).