Brain Health and Aphasia Recovery

Abstract
Language impairments can vary considerably between individuals with aphasia. Our neurobiological
models based on the stroke lesion can only partly explain the aphasic symptoms. We hypothesize that the
integrity of the residual brain tissue outside the stroke lesion is an important, but not yet fully appreciated,
determinant of aphasia severity and recovery.
It is well recognized that cardiovascular risk factors lead to cumulative widespread brain damage
through small vessel disease (SVD). Outside the aphasia literature, SVD has been strongly associated with
poor cognitive reserve and reduced resiliency to various forms of neurological injury. Stroke survivors with
aphasia typically have cardiovascular risk factors and they commonly exhibit SVD. However, the impact of
SVD is not usually taken into account in our models of recovery, even though the residual brain tissue is
responsible for overcoming the loss of function. It follows that higher degrees of SVD outside the lesion may
lead to worse aphasic symptoms and less chances of recovery due to reduced capacity to compensate for the
stroke injury. Our goal is to directly test this hypothesis.
We propose to evaluate how aphasia is shaped by the stroke lesion in combination with residual brain
integrity. Neuroimaging (brain MRI) is ideally suited to address this problem. SVD is composed of
microangiopathic ischemic changes and microhemorrhages. The ischemic changes from SVD can be
measured through white matter hyper intensities using T2-weighted and T2-FLAIR images, and the
microhemorrhages can be assessed using susceptibility-weighted images. SVD preferentially affects white
matter and diffusion MRI can provide additional measures of white matter microstructural integrity and their
relationship with the whole brain neuronal networks architecture (the brain connectome).
Using our experience with post-stroke lesion symptom mapping, white matter and connectome imaging
we propose a comprehensive study of the neurobiology and impact of SVD in aphasia. Our project will build on
international guidelines for SVD assessment (The STandards for ReportIng Vascular changes on
nEuroimaging - STRIVE) and it will develop an innovative multimodal machine learning approach to fully
assess brain integrity.
Brain integrity and language measures will be assessed in the context of chronic (Project 1) and acute
(Project 2) aphasia recovery. The behavioral and linguistic assessments will be guided by Project 4. With the
neuroimaging core, we will develop and distribute a multimodal neuroimaging approach to quantify the severity
and location of SVD.
Specific Aim 1 will longitudinally assess the independent impact of SVD, controlling for the brain lesion,
on acute and chronic symptoms, as well as acute and chronic language recovery. Specific Aim 2 will evaluate
the mechanisms by which SVD leads to language impairments by assessing the impact of SVD and stroke
lesions on connectome neural network architecture, loss of associative long-range white matter fibers and its
relationship with semantic, lexical-semantic, lexical-phonological, phonological/phonetic deficits.

Grant Number: 5P50DC014664-10
NIH Institute/Center: NIH
Principal Investigator: Leonardo Bonilha