Aging effects on the neural coding of proactive and reactive cognitive control: Administrative Supplement

Washington University, Saint Louis MO

Investigators

Abstract

Project Summary This proposal explores the neural and psychological mechanisms that underlie the well-established declines in cognitive control function experienced by otherwise healthy older adults. A clear consensus in the cognitive neuroscience of aging is that age-related cognitive control declines reflect neurobiological changes that occur in the functioning of the mid-brain dopamine system, interacting with targets located in the lateral prefrontal cortex (lPFC) and anterior cingulate cortex (ACC). The current proposal adopts an innovative experimental approach to this issue, by leveraging the methodology of representational similarity analysis (RSA), to examine the neural coding of cognitive control and how it changes with advancing age. Specifically, we utilize RSA to test the Dual Mechanisms of Control (DMC) theoretical framework, which postulates that older adults will exhibit clear impairments in the engagement of proactive control, but relative preservation of reactive control. The project directly tests this hypothesis, employing novel theoretically-optimized variants of the work- horse color-word Stroop paradigm, combined with RSA methods, to examine the neural mechanisms associated with proactive and reactive control, using a multi-modal neuroimaging approach involving matched fMRI and EEG studies. This multi-modal approach enables a systematic and comprehensive test of the DMC framework, to test whether proactive and reactive control have distinct temporal dynamic signatures, and involve anatomically dissociable neural mechanisms within the lPFC and ACC. We further propose to enrich our understanding of the mechanisms of age-related change in cognitive control function, by capitalizing on recent advances in the ability to assess risk of preclinical Alzheimer’s Disease (AD) and AD-related neurodegeneration through the use of blood plasma-based biomarkers. Through new collaborations with Dr. Brian Gordon, Dr. Ryan Bogdan, and Dr. Suzanne Schindler, we will utilize state-of-the-art methods, including single-molecule array (Simoa) and mass spectrometry, to comprehensively assess key blood-based biomarkers related to amyloid (APOE, beta-amyloid), tau (ptau181), and neurodegeneration (NfL, GFAP), as well as anatomical MRI biomarkers (e.g., cortical thickness). We propose an Administrative Supplement to provide additional support for us to acquire, process and rigorously analyze AD-related biomarker data. This Supplement will dramatically enhance the scope, impact, and