Language
English
Publication Date
12-1-2025
Journal
NeuroImage: Reports
DOI
10.1016/j.ynirp.2025.100289
PMID
41030378
PMCID
PMC12478081
PubMedCentral® Posted Date
9-17-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Apathy is characterized by loss of motivation and manifests as a reduction of goal-directed behavior. Apathy is highly prevalent across neurodegenerative diseases, including Alzheimer's Disease (AD) and Parkinson's Disease (PD), and is an important contributor to the disability and reduce quality of life in these conditions. The treatment of apathy remains challenging due to a lack of specific therapies, largely attributed to an incomplete understanding of its cognitive and neuroanatomical underpinnings, crucial for developing targeted interventions. Apathy can be mechanistically studied through effort-based decision-making (EBDM) paradigms, where individuals choose between low- and high-effort tasks for varying reward magnitudes. Anatomically, apathy has been associated with alterations in brain regions previously implicated in EBDM. Using a novel transdiagnostic study design in individuals with AD and PD, we aim to: (1) evaluate the independent effects of reward and effort sensitivity as a mechanistic link between apathy and neurodegeneration of basal ganglia-frontal networks and, (2) in a subset of PD patients receiving deep brain stimulation (DBS) surgery, determine whether electrical manipulation of subthalamic nucleus and/or DBS connectivity, directly alter reward and effort information processing and, consequently, goal-directed behavior. Understanding how neurodegeneration-alone or in combination with neuromodulatory interventions-drives apathy, is essential for guiding clinical decision-making and therapeutic development. Given its prevalence across neurodegenerative disorders, apathy provides a unique framework for investigating shared and disease-specific neuroanatomical, functional, and behavioral mechanisms. In this protocol paper, we describe the rationale and methodology of our proposed multimodal approach, to investigate apathy in a transdiagnostic cohort of individuals with AD and PD.
Keywords
Apathy, Alzheimer's disease, Parkinson's disease, Goal-directed behavior, Drift diffusion model, Magnetic resonance imaging, Tractography
Published Open-Access
yes
Recommended Citation
Gazes, Yunglin; Suzuki, Hideo; Morris, Lee-Anne; et al., "A Transdiagnostic, Multi-Modal Approach to Understanding Apathy: Methodological and Analytical Framework" (2025). Faculty and Staff Publications. 5268.
https://digitalcommons.library.tmc.edu/baylor_docs/5268