Description (from grant(s)):

Stroke is the leading cause of adult disability in the United States, making it a major public health concern (1). Approximately a quarter of all chronic stroke survivors present with aphasia, a language disorder caused by damage to the speech and language areas of the brain (3, 4). In a recently published report, Simmons-Mackie (1) estimates that over two million people in North America are currently living with aphasia. Stroke is typically thought to affect older persons; however, the incidence of stroke in younger individuals has been steadily increasing (2). In fact, at least half of all stroke patients in the state of South Carolina are under the age of 60 (2). Aphasia can vary in severity from very profound impairment that renders patients mute and without the ability to understand others’ speech, to milder forms where patients have great difficulty retrieving specific words. In the chronic stage of stroke, aphasia has been identified as the strongest predictor of poor quality of life. Aphasia not only influences the ability to communicate with family and friends, but also drastically decreases education and employment opportunities. Although some degree of spontaneous recovery from aphasia is typical in the first weeks and months following stroke, many patients are left with devastating communication problems and never fully recover. 

To address the need for studies improving long-term outcomes in aphasia, the Center for the Study of Aphasia Recovery (C-STAR), funded for just under four years at the time of this application, has made great progress towards understanding the mechanisms that promote spontaneous and therapy-induced recovery in aphasia. The overarching goal of the research proposed in this renewal application is to maintain our focus on aphasia therapy. Specifically, during the next funding phase, the focus of C-STAR is to improve access to aphasia therapy, enhance the effect of behavioral aphasia therapy to promote an improved aphasia therapy outcome, and understand overall health and neurolinguistic factors that influence aphasia recovery. To accomplish our research goals, this project will continue to rely on collaboration among five main investigators: Drs. Julius Fridriksson, Argye Hillis, Leonardo Bonilha, Chris Rorden, and Greg Hickok. Projects led by Fridriksson (chronic patients) and Hillis (acute patients) will continue to focus on factors that may promote improved outcome of aphasia therapy. Both projects have proven successful in yielding a vast, unique dataset including measures of brain status and response to aphasia therapy. Relying on this dataset, Bonilha and Rorden’s project will focus on the relationship between brain health and recovery from aphasia, whereas Hickok will utilize the same data to better understand aphasic impairment in relation to aphasia therapy success as well as new neurolinguistic models of speech and language processing.

Speech and language treatment (SALT) can be helpful in restoring language function, but recovery is often incomplete. Recent studies indicate that the effectiveness of SALT can be augmented by concurrent Transcranial Direct Current Stimulation (tDCS), a noninvasive, non-painful, electrical stimulation of the brain. It is believed that tDCS boosts neural plasticity that underlies recovery with SALT. This research will lay the groundwork for designing a Phase III clinical trial of tDCS + language therapy for aphasia early after stroke.

Liu CF, Hsu J, Xu X, Ramachandran S, Wang V, Miller MI, Hillis AE, Faria AV. Deep learning-based detection and segmentation of diffusion abnormalities in acute ischemic stroke. Communications medicine. 2021 December;1:61. PMCID: PMC9053217. 

Fan H, Su P, Lin DDM, Goldberg EB, Walker A, Leigh R, Hillis AE, Lu H. Simultaneous Hemodynamic and Structural Imaging of Ischemic Stroke With Magnetic Resonance Fingerprinting Arterial Spin Labeling. Stroke. 2022 June;53(6):2025. PMCID: PMC9179092. 

Liu P, Baker Z, Li Y, Li Y, Xu J, Park DC, Welch BG, Pinho M, Pillai JJ, Hillis AE, Mori S, Lu H. CVR-MRICloud: An online processing tool for CO2-inhalation and resting-state cerebrovascular reactivity (CVR) MRI data. PLoS One. 2022 Sep 28;17(9):e0274220. PMCID: PMC9518872.

Liu CF, Hsu J, Xu X, Kim G, Sheppard SM, Meier EL, Miller MI, Hillis AE, Faria AV. Digital 3D Brain MRI Arterial Territories Atlas. Sci Data. 2023 Feb 4;10(1):74. PMCID: PMC9899211. 

Breining BL, Faria AV, Tippett DC, Stockbridge MD, Meier EL, Caffo B, Hermann O, Friedman R, Meyer A, Tsapkini K, Hillis AE. Association of Regional Atrophy With Naming Decline in Primary Progressive Aphasia. Neurology. 2023 Feb 7;100(6):e582-e594. PMCID: PMC9946192. 

Liu CF, Li J, Kim G, Miller MI, Hillis AE, Faria AV. Automatic comprehensive aspects reports in clinical acute stroke MRIs. Sci Rep. 2023 Mar 7;13(1):3784. PMCID: PMC9992659. 

Kim G, Vitti E, Stockbridge MD, Saver JL, Hillis AE, Faria AV. Association of inferior division MCA stroke location with populations with atrial fibrillation incidence. Heliyon. 2023 Apr;9(4):e15287. PMCID: PMC10113841. 

Xu F, Liu D, Zhu D, Hillis AE, Bakker A, Soldan A, Albert MS, Lin DDM, Qin Q. Test-retest reliability of 3D velocity-selective arterial spin labeling for detecting normal variations of cerebral blood flow. Neuroimage. 2023 May 1;271:120039. PMCID: PMC10150252. 

Hou X, Guo P, Wang P, Liu P, Lin DDM, Fan H, Li Y, Wei Z, Lin Z, Jiang D, Jin J, Kelly C, Pillai JJ, Huang J, Pinho MC, Thomas BP, Welch BG, Park DC, Patel VM, Hillis AE, Lu H. Deep-learning-enabled brain hemodynamic mapping using resting-state fMRI. NPJ Digit Med. 2023 Jun 21;6(1):116. PMCID: PMC10284915.

Liu CF, Zhao Y, Yedavalli V, Leigh R, Falcao V, Miller MI, Hillis AE, Faria AV. Automatic comprehensive radiological reports for clinical acute stroke MRIs. Commun Med (Lond). 2023 Jul 10;3(1):95. PMCID: PMC10333348. 

Liu CF, Leigh R, Johnson B, Urrutia V, Hsu J, Xu X, Li X, Mori S, Hillis AE, Faria AV. A large public dataset of annotated clinical MRIs and metadata of patients with acute stroke. Sci Data. 2023 Aug 22;10(1):548. PMCID: PMC10444746. 

Zhu D, Xu F, Liu D, Hillis AE, Lin D, van Zijl PCM, Qin Q. Evaluation of 3D stack-of-spiral turbo FLASH acquisitions for pseudo-continuous and velocity-selective ASL-derived brain perfusion mapping. Magn Reson Med. 2023 Sep;90(3):939-949. PMCID: PMC11054979. 

Stockbridge MD, Matchin W, DeLuque E, Sharif M, Fridriksson J, Faria AV, Hillis AE. Mary has a little chair: Eliciting noun-modifier phrases in individuals with acute post-stroke aphasia. Aphasiology. 2024;38(5):771-789. PMCID: PMC11034753. 

Fan H, Bunker L, Wang Z, Durfee AZ, Lin D, Yedavalli V, Ge Y, Zhou XJ, Hillis AE, Lu H. Simultaneous perfusion, diffusion, T(2) *, and T(1) mapping with MR fingerprinting. Magn Reson Med. 2024 Feb;91(2):558-569. PMCID: PMC10872728. 

Raman A, Faria AV, Colavito M, Hillis AE. Novel Insights into Viewer-Centered Versus Stimulus-Centered Hemispatial Neglect: A Cross-Sectional Behavioral and Imaging Study of Acute Stroke. Brain Sci. 2025 Feb 17;15(2):208. PMCID: PMC11853268.