Over the past nine years we have developed a unique methodology for studying brain structure/function relationships, by studying 708 patients with acute or evolving left hemisphere stroke, initially within 24 hours of onset of symptoms with diffusion-weighted imaging (DWI), perfusion weighted imaging (PWI), and with batteries of language tasks. We have then studied them longitudinally with both imaging and language tests to identify changes in language that correlate with changes in blood flow in the brain. This work has led to novel insights into both the anatomy of the neural networks that support language and how these networks change over time. The networks are sometimes restored to their normal structure in response to restored blood flow and are sometimes reorganized, such that new areas assume the function of the damaged areas during the first year of recovery. In this renewal we aim to combine our unique methodology of studying the neural bases of language (evaluating changes in perfusion with concurrent changes in language performance) with both task-related and resting state functional connectivity MRI (rsfcMRI) to investigate the neural basis of recovery of naming, spelling, lexical-semantics, and sentence comprehension over the first year after stroke. We believe that by combining careful analysis of the changes in cerebral blood flow (in response to stroke or stroke treatment) with the changes in activation (measured by the hemodynamic response), changes in resting state connectivity (measured by correlations in the hemodynamic response in various areas at rest), and changes in anatomical connectivity, we will develop a better understanding of language recovery over the first year after stroke. Task-related fMRI and rsfcMRI provide distinct windows on recovery, and have different advantages. For example, rsfcMRI does not require any response and can be obtained in patients with even severe language deficits. Task-related fMRI reveals brain areas that can be recruited in various activities.
Aim 1 will identify changes in neural activation associated with naming, spelling, lexical-semantics, and sentence comprehension at Day 3, Week 2, Month 6, and Year 1 after stroke onset in patients with infarcts and/or hypoperfusion involving left thalamus, other purely subcortical areas, or any one of three "language cortex regions of interest (ROIs)": inferior frontal gyrus (IFG), superior temporal gyrus (STG), or fusiform gyrus (FG).
Aim 2 will identify, in the first three days of stroke, language and neural (imaging) predictors of subsequent language recovery.
Aim 3 will identify imaging biomarkers of language recovery at Months 6 and 12. It is hoped that this multidimensional model of recovery will serve in the future as the basis for targeted brain-based interventions for aphasia, which require an understanding of the anatomy of language networks, as well as the extent and timing of how these networks reorganize after injury.

Public Health Relevance

The aim of this application is to better understand how people who have language impairments cause by stroke improve during the first year. We know from our previous research on blood flow imaging that some of their improvement is due to restoring blood flow to parts of the brain that are important for language, while functional imaging research shows that some recovery is due to reorganization of language circuitry. We plan to combine blood flow imaging with functional imaging to develop a complete picture of recovery, to develop new treatments for language problems due to stroke in the future.

National Institute of Health (NIH)
Research Project (R01)
Project #
Application #
Study Section
Language and Communication Study Section (LCOM)
Program Officer
Cooper, Judith
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Johns Hopkins University
Schools of Medicine
United States
Zip Code
Bonekamp, David; Barker, Peter B; Leigh, Richard et al. (2015) Susceptibility-based analysis of dynamic gadolinium bolus perfusion MRI. Magn Reson Med 73:544-54
Sebastian, Rajani; Schein, Mara G; Davis, Cameron et al. (2014) Aphasia or Neglect after Thalamic Stroke: The Various Ways They may be Related to Cortical Hypoperfusion. Front Neurol 5:231
Sebastian, Rajani; Gomez, Yessenia; Leigh, Richard et al. (2014) The roles of occipitotemporal cortex in reading, spelling, and naming. Cogn Neuropsychol 31:511-28
Leigh, Richard; Krakauer, John W (2014) MRI-guided selection of patients for treatment of acute ischemic stroke. Curr Opin Neurol 27:425-33
Pettigrew, Corinne; Hillis, Argye E (2014) Role for Memory Capacity in Sentence Comprehension: Evidence from Acute Stroke. Aphasiology 28:1258-1280
Leigh, Richard; Jen, Shyian S; Hillis, Argye E et al. (2014) Pretreatment blood-brain barrier damage and post-treatment intracranial hemorrhage in patients receiving intravenous tissue-type plasminogen activator. Stroke 45:2030-5
Hickok, Gregory; Rogalsky, Corianne; Chen, Rong et al. (2014) Partially overlapping sensorimotor networks underlie speech praxis and verbal short-term memory: evidence from apraxia of speech following acute stroke. Front Hum Neurosci 8:649
Beslow, Lauren A; Ichord, Rebecca N; Gindville, Melissa C et al. (2014) Frequency of hematoma expansion after spontaneous intracerebral hemorrhage in children. JAMA Neurol 71:165-71
Beslow, Lauren A; Ichord, Rebecca N; Gindville, Melissa C et al. (2014) Pediatric intracerebral hemorrhage score: a simple grading scale for intracerebral hemorrhage in children. Stroke 45:66-70
Tippett, Donna C; Niparko, John K; Hillis, Argye E (2014) Aphasia: Current Concepts in Theory and Practice. J Neurol Transl Neurosci 2:1042

Showing the most recent 10 out of 65 publications