Rigid Preoccupations in Right Temporal Degeneration: Phenomenology and Neural Mechanisms

University Of California, San Francisco, San Francisco CA

Investigators

Abstract

ABSTRACT Some individuals with behavioral variant frontotemporal dementia (bvFTD) and semantic variant primary progressive aphasia (svPPA) syndromes are known to develop an intense, narrowed focus on specific activities, interests, and ideas, which together can be termed “rigid preoccupations” (RP). Examples of these behaviors include preoccupation with puzzles or games, collecting objects, dietary and exercise fads, religious or political adherence, clock watching, preoccupation with saving gasoline or electricity, and many others. Despite the very high early prevalence rates and clinical significance of RP behaviors in a subset of persons with dementia (PWD), particularly those with right temporal lobe dysfunction where RP symptom rates approach 90%, there is still no consensus in the field on the precise phenomenology of RPs from a behavioral neurology or neuropsychological perspective, and thus no agreement on how to measure them. The absence of validated measurement tools for comprehensively characterizing RP-related symptoms, and a lack of understanding of the fundamental neural circuitry involved in different presentations of this behavior, have hampered diagnosis and phenotyping, clinical research, clinical trial recruitment and monitoring, and clinical care of PWDs. For this study, we propose to perform a comprehensive evaluation of the phenomenology of RP symptoms using qualitative ethnographic methods, and to perform a chart review of archival research reports that can be analyzed in conjunction with functional MRI data. This work will set the foundation for later development of neurologically-grounded measures of RPs after this project. For Aim 1, we will perform a qualitative study to clarify the phenomenology of RPs using standard ethnographic methods. We will enroll 30 PWDs known to engage in RP behaviors, and will conduct interviews and home-based participant observation with them and their caregivers to elucidate their motivating emotions and thought processes. Interviewers will take observational field notes and conduct qualitative interviews with both PWDs and caregivers. Analytic memos will be constructed for each dyad to guide identification of themes. Transcribed interviews and field notes will be coded in ATLAS.ti, adding new codes as they emerge inductively. In parallel for Aim 2, we will perform a retrospective chart review of research visit summary reports from 200 PWDs (100 bvFTD/100 svPPA), quantifying evidence of RP behaviors and their associated cognitive and emotional processes. Data from the chart review will then be analyzed in conjunction with previously collected resting-state MRI scans to perform a preliminary examination of the neural basis of RP- associated features using functional connectivity and dynamic causal modeling approaches. Our goal is to understand the phenomenology of RP behavior in a data-driven manner using mixed-method approaches robust enough to capture the complexity of the internal cognitive and emotional processes involved, which will facilitate more meaningful hypotheses about the neurologic mechanisms underlying RPs and guide development of better measurement tools, facilitating advances in both research and clinical care.