Brain Markers Predicting Reading Recovery After Stroke
Condition: Left-Hemisphere Stroke
MeSH terms: Stroke
Study type: Observational

Summary: 
      For millions of stroke survivors acquired reading deficits represent a significant handicap
      preventing them from returning to work or continuing their education. The goal of the
      proposed research is to investigate what brain mechanisms enable recovery of impaired
      reading. To achieve this goal, the project will directly measure changes in brain perfusion
      (blood flow) and activation among recovering stroke survivors using a neuroimaging technique
      called perfusion fMRI (functional Magnetic Resonance Imaging). The project will test if
      re-perfusion (return of circulation) and re-appearance of reading-related brain activity in
      the left-brain network for reading is associated with recovery. The ability to predict
      recovery from neuroimaging has tremendous value in rehabilitation for generating prognoses.
      It may also dramatically improve the quality of research evaluation for novel, targeted
      interventions such as noninvasive brain stimulation or pharmacologic therapies.
    

Detailed description: 
      There is a fundamental gap in understanding the neuro-behavioral time-course of reading
      recovery following stroke. It is not known whether recovery of reading is associated with
      improved blood circulation and neural activity of the peri-infarct area, or whether
      circulation in the unaffected, contralateral brain areas contributes to functional recovery.
      Continued existence of this gap represents an important problem because, until it is filled,
      knowledge about optimal timing and targets for restorative therapies to improve reading will
      remain out of reach. The long-term goal is to develop clinical prognostic and therapeutic
      tools to improve reading limitations. The overall objective of this project is to
      characterize the neural mechanisms of recovery from stroke-induced reading impairments. The
      central hypothesis of this study is that subacute-to-chronic recovery of reading ability is
      potentiated by reperfusion (improved blood flow) of the left reading network. Reperfusion
      promotes the return of neural activity and supports behavioral recovery. In contrast,
      increased perfusion of the right brain areas represents a maladaptive response and is
      associated with worse chronic reading ability. This hypothesis has been formulated on the
      basis of preliminary data. The rationale for the proposed research is that once the neural
      recovery from stroke-induced reading impairments is characterized, clinicians will be able to
      predict individual recovery potential and select appropriate rehabilitation goals. Guided by
      strong preliminary data, this hypothesis will be tested by pursuing two specific aims: 1)
      Determine whether post-stroke changes in cerebral blood flow predict recovery of reading
      ability; and 2) Determine whether increased baseline perfusion of the left reading network is
      paralleled by greater reading-related neural activation. Under the first aim, perfusion in
      the peri-infarct tissue, left reading network, and homologous right brain areas will be
      examined among left stroke patients with reading impairments. A non-invasive measure of
      perfusion (Arterial Spin Labeling, ASL MRI) will be applied longitudinally: <4 weeks
      post-stroke (sub-acute) and >3 months post-stroke (chronic) to test if increased perfusion of
      the left reading network is coupled with an improvement of reading accuracy. Under the second
      aim, reading-induced brain activity will be recorded in the same group of patients using
      perfusion-based functional MRI. The effect of task-related neural activity on recovery will
      be separated from the effect of cerebral blood flow by statistically controlling for baseline
      circulation and by modeling independent contributions of perfusion and BOLD (Blood Oxygen
      Level Dependent) signals in order to estimate cerebral oxygen consumption rate, which is
      directly related to neural activity. The conceptual innovation of this study is that it
      offers the opportunity to examine reading recovery as distinct from other functions. The
      methodological innovation is in using simultaneously-acquired perfusion and BOLD signals,
      helping to measure longitudinal changes in circulation and neural activity with unprecedented
      precision. The proposed research is significant because it can help greatly improve the
      effectiveness of post-stroke rehabilitation.
    

Intervention name(s): Perfusion functional Magnetic Resonance Imaging (perfusion fMRI)
Intervention type(s): Diagnostic Test
Intervention description(s): The goal of this test is to measure brain activity during subacute and chronic post-stroke period using a widely available non-invasive neuroimaging tool - functional Magnetic Resonance Imaging (fMRI). Because fMRI relies in part on cerebral blood flow, which is altered in stroke, measuring longitudinal changes in neural activity with fMRI requires that we control for concomitant changes in blood circulation. To do this, we will employ a novel dual-echo perfusion fMRI sequence, which will allow us to separately estimate neural and vascular contributions to fMRI.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        34 participants with first-ever left-brain stroke
      
Keywords: stroke; reading; fMRI; perfusion; activation; BOLD; recovery; subacute; chronic