More than 2.5 million people in the U.S. have aphasia, a language disorder most often caused by stroke that dramatically affects an individual’s functional independence and quality of life. For several decades, fMRI has critically advanced aphasia research, but it has notable limitations. For example, individuals with conditions that affect many Veterans (e.g., implanted medical devices or a history of injury involving metal) cannot safely be scanned. These individuals have therefore been systematically excluded from fMRI studies of aphasia. Additionally, fMRI is conducted in a noisy, restrictive environment, necessitating the use of artificial experimental paradigms that may not engage the full range of anatomical and physiological mechanisms supporting real-world language and communicative function. In contrast to fMRI, functional near-infrared spectroscopy (fNIRS) has few contraindications, is silent, inexpensive, and can be administered in a standard clinic room with naturalistic language paradigms. Despite these advantages, fNIRS has rarely been used to study aphasia, likely due to a lack of data validating it as compared to fMRI in this specific population. This study will address critical gaps in the evidence that would support fNIRS’ use by investigating its correlation with fMRI for language mapping (Aim 1), its test-retest reliability (Aim 2), and its sensitivity to changes in brain function due to behavioral language treatment (Aim 3) in people with chronic post-stroke aphasia. In part A of this study, 24 people with chronic aphasia (PWA) will be scanned twice over a 3-week interval with both fNIRS and fMRI while performing three language tasks: picture naming and semantic and phonological matching. Concurrent validity will be established by correlating language activation measured by fNIRS with that of fMRI. fNIRS’ test-retest reliability will be assessed by computing intraclass correlation coefficients across the first and second fNIRS scans, with comparable comparisons of the fMRI scans. Twenty- four healthy older adults will complete the same protocols to inform interpretations of the results in PWA. In part B, 12 PWA will complete fNIRS and fMRI scans during language tasks before and after three weeks of intensive language therapy, administered as part of a separate clinical trial of treatment for word-retrieval impairments. Comparisons between pre- and post-treatment fNIRS and fMRI scans will be used to assess fNIRS’ sensitivity to change after intervention, relative to that of fMRI. Behavioral research activities (including intensive language therapy) will be conducted at the VA Pittsburgh Healthcare System (VAPHS). fMRI and fNIRS will be performed at the CMU-Pitt Brain Imaging Data Generation & Education Center and the Brain and Auditory Sciences Research Initiative at the University of Pittsburgh, respectively. The results of this study will help determine the viability of fNIRS for measuring language functions in post-stroke aphasia and may provide a foundation for increased use of fNIRS in aphasia research, broadening participation in neuroimaging studies and increasing the generalizability of their findings. The results may also support the development of novel uses for fNIRS, such as measuring brain responses during everyday language use or aphasia treatment, and using real-time neurofeedback as an adjuvant to behavioral aphasia therapy. The applicant is a VA CDA-1 awardee, research and clinical speech pathologist, and former Advanced Geriatrics Fellow in the Geriatric Research, Education, and Clinical Center at VAPHS, with experience in aphasia rehabilitation and fMRI. During the CDA-2, mentorship and structured training activities in advanced neuroimaging/fNIRS methods, advanced statistics, Bayesian adaptive clinical trials design, and validity theory will facilitate execution and completion of the project and achievement of the applicant’s career goals. These goals include completing a CDA-2 and becoming an independent VA clinician-scientist supported by VA Merit Review and NIH/NIDCD award mechanisms, with a research program focused on improving service delivery and maximizing treatment outcomes for Veterans and others with aphasia.

Aphasia is a debilitating and often chronic language disorder that has dramatic consequences for communication and quality of life. Aphasia affects more than 2.5 million Americans, including thousands of U.S. Veterans. Given evidence that stroke, the leading cause of aphasia, is more common in Veterans than non- Veterans, VA has a vested interest in developing and implementing novel prognostic and therapeutic tools for aphasia management. Research on the brain systems implicated in aphasia and its rehabilitation has relied heavily on fMRI, but fMRI has contraindications that are exclusionary for many people with aphasia. This project aims to validate functional near-infrared spectroscopy (fNIRS), a lower-cost, less-restrictive neuroimaging technology that could reduce barriers to the use of neuroimaging in research and clinical care for Veterans with aphasia. The project will help establish the viability of fNIRS for studying, predicting, and potentially accelerating or augmenting aphasia rehabilitation, laying the groundwork for future clinical trials.