Aphasia is one of the most common neurological deficits after a stroke, typically resulting from injury to cortical brain regions related to language processing in the dominant hemisphere. However, many individuals with aphasia can exhibit language impairments that are out of proportion to the degree of gray matter injury, with severe deficits from relatively smaller subcortical lesions, or less severe deficits in spite of relatively large lesions. This discrepancy is frequently attributed to the notion that language relies not only on the integrity of gray matter regions, but also on the white matter pathways supporting their ability to act in concert. Nonetheless, white matter disconnections beyond the necrotic or gliotic post-stroke brain lesions are not always measured or taken into account in models of brain-behavior relationships. To fully understand the neurobiology of aphasia, brain damage should be quantified as the combination of direct necrosis / gliosis as well as cortical disconnection. The overarching purpose of this research proposal is to comprehensively map residual white matter networks in stroke survivors to determine their role in the neurobiology of language processing and aphasia recovery. Using newer advancements in structural neuroimaging, our group developed Connectome-Lesion Symptom Mapping (CLSM) to test specific questions related to aphasia mechanisms and aphasia recovery. During the first cycle of this project, this research yielded 15 high-impact peer-reviewed publications. Based on this success, the novel research proposed in this project will build on these achievements to evaluate three independent new conceptual topics related to aphasia: we will define multimodal network dynamic modeling approaches to elucidate the relationship between structural and functional neuronal network integrity post-stroke, including direct and indirect neuronal communication, and their relationship with aphasia (Aim 1). The dual stream model is a promising new theoretical framework for language processing, however, it is still an oversimplification and our recent data suggests that each stream is composed of finer grained sub-networks. Using the connectome approach, we will define the sub-networks that form the dorsal and ventral streams of language processing (Aim 2). We will determine stream-specific white matter microstructural network plasticity supporting aphasia recovery after treatment (Aim 3). To accomplish these aims, we will leverage a large baseline behavioral and imaging chronic aphasia dataset from the Center for the Study of Aphasia Recovery (C-STAR) (n-199) (Aims 1 and 2), and data from the ongoing treatment study Predictor of Outcome of Language Rehabilitation (POLAR) (n=150) (Aim 3). Overall, this project will build on connectome and network science to advance translational and personalized research in aphasia. It will advance knowledge on neuroimaging methods, provide mechanistic information about language processing, and determine markers for therapy-related language improvement.

Public Health Relevance

The severity of language processing difficulties after a stroke can be better understood by taking into account how brain networks have been affected by the stroke. Building on methodological advancements to map the whole brain networks in stroke survivors using neuroimaging, this research will optimize neuronal circuitry mapping in aphasia, define sub-networks associated with semantics and phonological processing, and lead to translational use of brain mapping to predict and explain therapy-mediated aphasia recovery.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Cooper, Judith
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Medical University of South Carolina
Schools of Medicine
United States
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Singh, Tarkeshwar; Phillip, Lorelei; Behroozmand, Roozbeh et al. (2018) Pre-articulatory electrical activity associated with correct naming in individuals with aphasia. Brain Lang 177-178:1-6
Peters, Denise M; Fridriksson, Julius; Stewart, Jill C et al. (2018) Cortical disconnection of the ipsilesional primary motor cortex is associated with gait speed and upper extremity motor impairment in chronic left hemispheric stroke. Hum Brain Mapp 39:120-132
Feenaughty, Lynda; Basilakos, Alexandra; Bonilha, Leonardo et al. (2017) Non-fluent speech following stroke is caused by impaired efference copy. Cogn Neuropsychol 34:333-346
McKinnon, Emilie T; Fridriksson, Julius; Glenn, G Russell et al. (2017) Structural plasticity of the ventral stream and aphasia recovery. Ann Neurol 82:147-151
Basilakos, Alexandra; Fridriksson, Julius; Rorden, Chris et al. (2017) Activity associated with speech articulation measured through direct cortical recordings. Brain Lang 169:1-7
Gleichgerrcht, Ezequiel; Fridriksson, Julius; Rorden, Chris et al. (2016) Separate neural systems support representations for actions and objects during narrative speech in post-stroke aphasia. Neuroimage Clin 10:140-5
Bonilha, Leonardo; Gleichgerrcht, Ezequiel; Nesland, Travis et al. (2016) Success of Anomia Treatment in Aphasia Is Associated With Preserved Architecture of Global and Left Temporal Lobe Structural Networks. Neurorehabil Neural Repair 30:266-79
Yourganov, Grigori; Fridriksson, Julius; Rorden, Chris et al. (2016) Multivariate Connectome-Based Symptom Mapping in Post-Stroke Patients: Networks Supporting Language and Speech. J Neurosci 36:6668-79
Fedorenko, Evelina; Fillmore, Paul; Smith, Kimberly et al. (2015) The superior precentral gyrus of the insula does not appear to be functionally specialized for articulation. J Neurophysiol 113:2376-82
Bonilha, Leonardo; Gleichgerrcht, Ezequiel; Fridriksson, Julius et al. (2015) Reproducibility of the Structural Brain Connectome Derived from Diffusion Tensor Imaging. PLoS One 10:e0135247

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