PROJECT SUMMARY—Language and Emotions: Discovery and Clinical Translation (Project ൬) In primary progressive aphasia (PPA) and behavioral variant frontotemporal dementia (bvFTD), symptoms can reflect the neurodegeneration of language and emotion brain networks. Although recent clinical and basic science evidence suggests there is substantial conceptual, mechanistic, and clinical overlap between the domains of language and emotion, research on these areas has largely proceeded in parallel. In patients who exhibit early alterations in both language and behavior, diagnostic accuracy can be limited because theoretical and anatomical models of the language-emotion interface are lacking. A central hypothesis of this proposal is that damage and decline in interacting language and emotion neural networks underlie symptoms in PPA, bvFTD, and emotional semantic variant frontotemporal dementia (esvFTD), a newly defined syndrome. Studies of PPA and bvFTD often do not include comprehensive assessments of both language and emotion systems because evaluation of these domains typically requires specialized, time-intensive approaches. A more detailed understanding of the clinical features that characterize these disorders at presentation, and the symptoms that emerge over time, will facilitate differential diagnosis and help to predict neuropathological subtypes, a critical step in the emerging era of molecular-specific therapies. Assessment tools that provide scalable, objective, and ultimately automated, measures of language and emotion functioning will be needed before these approaches can be used to monitor disease progression or treatment response in large-scale clinical trials. In the proposed project, we will leverage existing clinical, neuroimaging, and neuropathological data collected in previous PPG cycles and will collect new language and emotion (i.e., autonomic nervous system activity, facial expression, and emotional experience) data using innovative techniques. We will conduct three annual in-person evaluations and five semiannual remote longitudinal assessments of language and emotion in patients with PPA, bvFTD, and esvFTD and in age-matched healthy controls. We will use these data to refine current clinical conceptualizations of these disorders and to investigate how neural system decline relates to language and emotion trajectories across the clinical syndromes. We will also develop automated tools that extract objective measures of language and emotion, which will make these approaches more accessible to the community. We will address three key aims. In Aim ൬, we will advance current models of PPA, bvFTD, and esvFTD by integrating language and emotion measures. In Aim ൭, we will map longitudinal decline in language, emotion, and associated brain structures and networks in PPA, bvFTD, and esvFTD. In Aim ൮, we will create automated language and emotion tools that facilitate diagnosis, track progression, and predict pathology. The proposed projec...