Close to 2.5 million Americans are currently living with post-stroke aphasia, a debilitating communication disorder
affecting multiple language modalities. Most stroke survivors with aphasia have acquired reading deficits, which
persist chronically and severely limit life participation and autonomy. There is an urgent need for effective
treatments grounded in stroke neurobiology which yield robust functional improvements. Treatments targeting
impaired reading processes and aimed at restoring cerebral blood flow (CBF) can meet this need by directly
remediating dysfunctional brain mechanisms. In the proposed R01 we will combine aerobic exercise training
(AET) with an intensive phono-motor reading treatment (PMT). Our central hypothesis is that a single bout of
aerobic exercise will increase CBF and oxygenation, and if delivered before a PMT session, will facilitate
treatment-induced neuroplasticity, strengthening damaged phonological networks and leading to robust
functional improvements over time. We and others found that reduced CBF in parts of the left hemisphere outside
the stroke lesion persists for weeks to months after a stroke and predicts more severe language deficits and
worse recovery. Phonological processing, or the ability to derive sound structure of words, critical to so many
language modalities, is consistently impaired in left-hemisphere stroke survivors with aphasia and reding deficits.
We expect that the proposed treatment targeting both the impaired CBF, and phonological deficits will markedly
increase treatment effectiveness and enhance generalization to untrained language modalities. We will test our
central hypothesis by pursuing three specific aims. Under Aim 1, we will determine if combined AET and PMT
improve language outcomes by carrying out a randomized controlled trial in 70 individuals with chronic left-
hemisphere stroke. Participants will complete either 20 minutes of moderate aerobic exercise or light stretching
prior to each session of intensive PMT. We expect that while both groups should improve, the AET group will
show more robust language improvements after 40 sessions of combined AET+PMT. Under Aims 2-3, we will
study both the immediate and sustained impact of AET and PMT on brain function using 3 MRI scans,
administered before the intervention, after the initial aerobic exercise session, and after the full course of AET +
PMT treatment. We expect that aerobic exercise will have an immediate positive impact on CBF and resting
state functional connectivity, as well as induce a sustained improvement in these measures and in task-related
brain activity compared to the pre-intervention baseline. While each of these interventions in isolation has shown
positive impact on stroke recovery, the proposed project will test if AET promotes acquisition and retention of
therapy skills when adjuvant to PMT. This has the potential to radically change how these treatments are applied,
increasing their effectiveness, and ultimately improving the lives of 2.5 million Americans living with stroke-
related aphasia. In addition, it is likely that the results will contribute to the understanding of stroke recovery
mechanisms thereby fundamentally advancing the field of neurorehabilitation.
