A new synthesis of aberrant reward processing in frontotemporal dementias

Abstract Background Aberrant reward processing is a cardinal feature of frontotemporal dementias (FTD), driving abnormal socio‐emotional behaviours that define these diseases clinically. However, the hedonic architecture of FTD remains poorly characterised. Here we addressed this issue for a multimodal spectrum of hedonic behaviours in a large patient cohort representing all major syndromes of FTD. Method Twenty‐seven patients with behavioural variant (bv)FTD and 58 with primary progressive aphasia (PPA) (24 non‐fluent variant (nfvPPA), 22 semantic (svPPA), 12 logopenic (lvPPA)) were studied in relation to 34 patients with typical Alzheimer’s disease (AD) and 42 healthy controls. Patients’ caregivers completed a questionnaire recording changes in liking and/or interest in stimuli or activities with primary (appetite/sweet tooth, sex) or non‐primary (music, religion, art, colour) reward value. We applied multiple correspondence analysis (MCA) to map the relationships between hedonic domains and extract core factors defining aberrant hedonic phenotypes. Voxel‐based morphometry (VBM) was used to define neuroanatomical substrates across the patient cohort. Result The most striking hedonic phenotypes defined bvFTD and svPPA: whereas both syndromes were characterised by altered hedonic valuation of food, they were polarised by their profiles in other hedonic domains (bvFTD ‐ decreased interest in sex and music, altered interest in art and colour; svPPA ‐ increased interest in sex, religion and music). Across the combined participant cohort, one MCA factor largely accounted for the presence of hedonic alterations: this factor was linked to a diverse repertoire of appetitive and socio‐emotional behaviours (apathy, disinhibition, inappropriate humour and affection) and underpinned by grey matter loss in a distributed frontotemporal and subcortical network anchored in right anterior temporal cortex. A second MCA factor largely determined the polarity of altered hedonic valuation (approach vs avoidance). Conclusion Our findings define new, multimodal hedonic phenotypes of bvFTD and svPPA and suggest a neurobiological synthesis in which involvement of right anterior temporal lobe and its connections drives the phenotypic expression of aberrant reward processing across the FTD and AD spectrum. This work has implications for the development of novel hedonic instruments and biomarkers in neurodegenerative diseases.