A Mechanistic Study to Investigate tDCS and Working Memory in MCI Patients - Project Summary/Abstract This K25 proposal is for a five-year mentored training program to launch Dr. Aprinda Indahlastari’s career as an independent aging investigator by leveraging her engineering background to develop personalized cognitive intervention in NIH-relevant research on cognitive aging and dementia. As such, the proposed training will transition Dr. Indahlastari into the field of aging and ADRD, by 1) acquiring knowledge in neurobiological effects of clinical aging and Alzheimer's disease and related dementias (ADRD) in the context of aging interventions, 2) gaining experience in clinical trial design focused on deploying aging interventions, 3) learning skills in advanced neuroimaging analytics with machine learning to probe and analyze intervention effects, and 4) becoming an independent investigator and forming a network of collaborators in clinical ADRD research. The training plan encompasses various components such as formal coursework, didactics, clinical cases shadowing, conferences, direct mentorship, and career development activities to facilitate candidate’s transition towards independence. The overarching research question addressed in this proposal is characterizing the effect of acute (one-time) application of transcranial direct current stimulation (tDCS) with standard fixed dosing on working memory performance and functional connectivity in individuals with mild cognitive impairment (MCI). Fixed dosing strategy refers to prescribing the same stimulation parameters to participants within a single study. To address this question, a human trial study will be conducted at the University of Florida to evaluate working memory gains with tDCS in MCI patients compared to healthy control. The study will employ state-of-the-art methods including person-specific computational models, machine learning, and multi-modal neuroimaging. The research proposal outlines two main aims to unravel the relationship between working memory gains and acute tDCS application in the MCI cohort. Aim 1.) Identify whether acute tDCS application leads to greater behavioral change in working memory and quantify important factors driving these changes in MCI patients compared to cognitively intact cohort. We hypothesize that acute tDCS may increase working memory performance during active tDCS and larger degree of brain atrophy and white matter hyperintensity observed in MCI patients will significantly decrease current intensity in stimulated brain regions. Aim 2.) Determine whether acute tDCS application strengthens functional connectivity within the working memory network. We hypothesize that acute tDCS may significantly increase functional connectivity within the working memory network during active stimulation, but not during sham stimulation, for both healthy and MCI cohorts. Machine learning enhanced models will be employed to identify important tDCS current characteristics that drive working memory gains and strengthen connectivity networks at individual level. The information gathered from this grant will provide a basis for future R01 submission to formulate custom intervention tailored to each individual. These personalized interventions are expected to be more effective than the standard fixed dosing strategy in improving overall cognitive abilities.
