Neuroplasticity Biomarkers in Aphasia

University of Wisconsin (UW)

Status: Enrolling

Conditions: Stroke; Language; Aphasia

Treatments: Behavioral: Pseudoword learning paradigm task

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06471127

2023-1101

Protocol Version 9/26/2025 (Other Identifier)

1K23DC021744 (U.S. NIH Grant/Contract)

L&S/COMMUN SCI & DISORDERS (Other Identifier)

A481800 (Other Identifier)

Details and patient eligibility

About

Patients with stroke frequently suffer from aphasia, a disorder of expressive and/or receptive language, that can lead to serious health consequences, including social isolation, depression, reduced quality of life, and increased caregiver burden. Aphasia recovery varies greatly between individuals, and likely relies upon the capacity for neuroplasticity, both at a systems level of reorganized brain networks and a molecular level of neuronal repair and plasticity. The proposed work will evaluate genetic and neural network biological markers of neuroplasticity associated with variability in aphasia, with a future goal to improve prognostics and identify therapeutic targets to reduce the long-term burdens of aphasia.

Full description

Aphasia is an acquired neurologic language disorder that is among the most challenging long-term disabilities for stroke survivors, often leading to social isolation and reduced quality of life. Recovery from aphasia relies on plasticity in residual brain networks. However, neuroplasticity varies substantially across individuals, making the presence, severity, and phenotype of language impairments challenging to predict. A vital step toward post-stroke precision medicine is identifying neuroplasticity-related biological markers that can improve prognostic models and targeted neurorehabilitation therapies for people with aphasia. The proposed research will test the central hypothesis that individual differences in neuroplasticity, measured through genetic polymorphisms and longitudinal neuroimaging connectivity biomarkers, will account for significant variance in post-stroke aphasia recovery. This 5-year project will include three specific aims. Aim 1 is to index spontaneous recovery by determining relationships between genetic biomarkers of plasticity, longitudinal neural network connectivity, and changes in language during sub-acute to chronic stroke recovery. Aim 2 is to identify genetic and MRI biomarkers predictive of chronic post-stroke aphasia severity and phenotypes. Aim 3 is to characterize genetic and MRI biomarkers associated with verbal learning variability in chronic aphasia. These data will support the development of a larger, multi-site R01 study to examine interactions between multiple biomarkers of neuroplasticity that inform longitudinal aphasia prognostics and treatment efficacy.

Enrollment: 90 estimated patients

Sex: All

Ages: 40 to 90 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Ages 40-90
2. Right-handed (prior to stroke)
3. Proficient English speakers
4. History of a single ischemic stroke in the middle cerebral artery territory that is lateralized to the left or right (Aim 1) cerebral hemisphere.
5. Presence of aphasia (Aims 2-3)
6. Capacity to understand the nature of the study and provide informed consent
7. Acute or subacute stroke at the time of Aim 1 enrollment; Stroke #12 months old (chronic) at the time of Aims 2-3 enrollment
8. Medically stable

Exclusion criteria

1. History of significant medical or neurological disorder (other than stroke)
2. History of significant or poorly controlled psychiatric disorders
3. Current abuse of alcohol or drugs, prescription or otherwise
4. Clinically significant and uncorrected vision or hearing loss
5. Anything other than standard of care stroke treatment such as Plavix, aspirin (81-300 mg daily), beta-blockers, diabetes medications or choles- terol-lowering agents, thrombolytics (e.g., tPA), anticoagulation agents such as Heparin, Warfarin/Coumadin

Trial design

Primary purpose: Other

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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90 participants in 1 patient group

Experimental word-learning task for aphasia

Experimental group

Description:

The word learning task includes 210 trials across 7 learning blocks (30 trials/block). Each trial features two novel objects (target and foil) on the screen, with an audio recording naming one object. Subjects must quickly and accurately identify the named object. Correct responses are rewarded with a happy face, and incorrect ones with a sad face. The target object's position is counter-balanced, and trial order is randomized for each subject. Short pauses occur every 60 trials to reduce fatigue. After 7 learning blocks, feedback is discontinued, and an immediate test block assesses word-referent recognition. A week later, a second test block, with the same instructions, measures retained learning. Each test block consists of 30 randomized trials without feedback.

Treatment:

Behavioral: Pseudoword learning paradigm task