Mechanism, connectivity, and outcome prediction of anxiety intervention from MRI-derived models in tDCS augmented cognitive training

Project Summary / Abstract Alzheimer’s disease (AD) is the most common form of dementia. The rate of dementia increases almost exponentially with age – thus, the prevalence of AD has rapidly grown with the global life expectancy. Dementia is detrimental to an individual’s standard of life, economic status, and psychological condition. Studies have

shown that certain neuropsychiatric disorders can promote the progression of mild cognitive impairment (MCI) to AD. These disorders include anxiety, depression, and apathy. Depression and apathy have been studied in this population; however, anxiety has largely been neglected. Understanding the mechanism, brain connectivity,

and response heterogeneity involved in anxiety interventions is pivotal in developing individualized interventions for anxiety-paired MCI or AD. This proposal broadly aims to understand the mechanism of anxiety interventions in an older adult population. The objective of this work is to compare the neural changes that occur in individuals who respond and do not

respond to the non-invasive intervention. This work focuses on transcranial direct current stimulation (tDCS) for anxiety intervention. Prior works have shown that tDCS shows promise to treat anxiety when paired with cognitive training. However, a greater understanding of its mechanisms is required to develop a consistent pipeline for this

intervention. Functional magnetic resonance imaging (fMRI) will be used to identify the regions of interest (ROIs) that are responsible for neurophysiological changes in tDCS-paired cognitive training for anxiety intervention (Aim 1). We focus on specific brain regions (DLPFC, DMPFC, VLPFC) that have been shown to lead to response

in previous anxiety and dementia studies. Our hypothesis is that these activity in these regions will be positively correlated to changes in neural function compared to sham. The neuroimaging results will highlight the specific functional connectivity networks (left or right DLPFC, ACC) in fMRI that are associated with response to cognitive

training and tDCS intervention (Aim 2). Our analysis target specific functional connectivity networks that are backed by anxiety research. These results will provide insight into the best intervention strategies to yield positive results to anxiety interventions. All together, these aims will provide crucial insight into anxiety pathways and the

ideal steps for targeted anxiety interventions to prevent AD and related dementia. This training proposal will provide the applicant with comprehensive training in effective teaching and mentoring techniques. She will foster her ability to collaborate seamlessly within interdisciplinary teams and hone the skills

necessary for disseminating research findings to both scientific and clinical audiences. The applicant will gain experience in designing and performing experiments that combine neural and cognitive outcome measures. These experiences will further exposure her to advanced machine learning and artificial intelligence together

with neuroimage analysis tools. Engaging in these experiences will enrich the applicant's technical and professional capabilities, equipping them with the essential training required for a prosperous career as research faculty in academia.