Neuroplasticity Biomarkers in Aphasia

University of Wisconsin, Madison90 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Eligibility

Sex: ALLMin age: 40 YearsMax age: 90 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Aphasia presence/severity

The primary outcome measure for Aim 1 will be overall aphasia severity. Severity across language domains will be measured by Western Aphasia Battery-Revised Aphasia Quotient (AQ). AQ scores range from 0-100 and rate severity as follows: 0-25 is very severe, 26-50 is severe, 51-75 is moderate, and 76+ is mild.

Time frame: 3 months, 6 months, 1 year post-stroke

Semantic processing

A primary outcome measure for Aim 2 will be semantic versus phonological processing ability. Semantic processing will be measured by the three pictures version of the Pyramids and Palm Trees Test (PPT) and Psycholinguistic Assessments of Language Processing in Aphasia (PALPA) 51: Word Semantic Association, and semantic weights will be calculated from Philadelphia Naming Test (PNT). PPT ranges from 0-52, with higher scores indicating a better ability to retrieve item names from semantic memory. PALPA 51 ranges from 0 to 40, with each correct semantic association earning one point. PNT semantic weights refer to the measure of the semantic relatedness of the words used in the test.