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Neurobiology of Language Re-learning in Post Stroke Aphasia Treatment

$49,538F31FY2025DCNIH

University Of Pittsburgh At Pittsburgh, Pittsburgh PA

Investigators

Abstract

Aphasia is a debilitating language disorder that affects over 2 million Americans1 and impairs communication and reduces quality of life. Behavioral language treatment protocols are the clinical standard for managing aphasia. These interventions aim to restore language functions through structured therapy. However, treatment outcomes vary widely2,3, and the mechanisms underlying treatment success remain unclear. Prior studies have identified several non-modifiable predictors of aphasia recovery, such as initial aphasia severity and lesion characteristics3,4. However, there are additional modifiable factors that may contribute to aphasia treatment response which have yet to be studied. Sleep-related memory consolidation may be one such factor. Sleep is required to stabilize labile memory traces for long-term retention, and its disruption impairs learning5. Stroke survivors frequently experience sleep disturbances6, but the impact of these disturbances on aphasia treatment outcomes has not been systematically evaluated. This project applies relevant principles of the Complementary Learning Systems (CLS) neurobiological framework to aphasia treatment as a model for understanding the contribution of sleep to aphasia treatment outcomes. The CLS is a dual systems model of learning that describes a division of labor between brain systems to support learning, in which newly learned information is initially stored in the hippocampus and is gradually consolidated to rely more on stable neocortical brain networks for long-term retention7,8. Sleep facilitates this hippocampal-to-neocortical shift, but it is unknown how well the core principles of CLS are upheld in the lesioned brains of individuals with aphasia. We will extend the relevant principles of the CLS framework to evaluate how sleep-related consolidation influences neural and behavioral response to aphasia treatment. Specific Aim 1 explores the role of sleep in behavioral and neural treatment outcomes by associating sleep quality with changes in naming performance and brain activation. Specific Aim 2 tests whether aphasia treatment promotes shifts in brain activation patterns in hippocampus and neocortex, and how these shifts are associated with behavioral improvements. Data from an ongoing clinical trial of intensive naming treatment will be used to address these aims. Data collection for this trial will be complete prior to beginning the proposed project. This study represents the first systematic investigation of sleep’s impact on aphasia treatment as well as a novel application of a neurobiological framework of learning to aphasia recovery. Findings could uncover modifiable mechanisms driving treatment-response variability, identifying new pathways for optimizing patient outcomes. Completing this research project and the associated training, the applicant will develop essential expertise, establishing herself as the first cognitive neuroscientist specialized in sleep and aphasia recovery.

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Neurobiology of Language Re-learning in Post Stroke Aphasia Treatment · GrantIndex