Stroke is the leading cause of long-term disability in the US and worldwide. Unilateral stroke of the left- hemisphere causes reading and language deficits in 21-58% of stroke survivors and these deficits persist chronically, despite participation in therapy. The majority of the available reading treatments show the clearest benefits on trained materials. Therefore, there is an urgent need for new treatment strategies that can generalize outside of the treatment context. Biologically-based interventions can meet this challenge by directly influencing beneficial post-stroke plasticity. For example, real-time functional Magnetic Resonance Imaging Neurofeedback (fMRI NFB) is an innovative approach allowing participants to regulate their own brain activity. It uses a combination of mental strategies and concurrent brain activity feedback. Studies have shown that repeated efforts to self-regulate brain activity lead to learning-induced neural changes. Preliminary evidence also suggests that real-time fMRI NFB can improve post-stroke motor and cognitive function. The main goal of the present proposal is to build on this success and to advance biologically-inspired interventions for reading. Strong preliminary data show that reduced recruitment of the intact left-hemisphere reading areas is associated with suboptimal reading outcomes after stroke. In addition, pilot data suggest that right hand finger tap imagery can effectively activate the left inferior parietal region thought to support binding of visual orthographic information with sound representations during reading. Given that difficulty with orthography- phonology conversion is the most common deficit among left-hemisphere stroke survivors, the current project proposes to use right hand finger tap imagery in combination with fMRI NFB to help re-instate left inferior parietal activity during reading. It is hypothesized that efforts to increase reading-related brain activation in the left-hemisphere will re-engage the impaired reading mechanisms and may alleviate reading deficits. Under this K01 award, the applicant will develop skills necessary to test this hypothesis, namely in carrying out clinical trials using fMRI NFB and motor imagery. This project has 3 specific aims. Under Aim 1, the applicant will become proficient in specific hardware, software, pre- and post-processing requirements of fMRI NFB, gain NFB research experience, and acquire critical skills in motor imagery and clinical trial design. In Aim 2, the applicant will apply this training to conduct a clinical trial feasibility study for a combined fMRI NFB and motor imagery rehabilitation of reading impairments in left-hemisphere stroke. Lastly, under Aim 3, the applicant will characterize the neural mechanisms of reading in subacute stroke. At the end of this award period, the applicant will develop a valid and reliable paradigm for a neuroscience-based reading intervention that has the potential to change how reading deficits are treated. The methods developed here could be extended to other domains and to other clinical populations to improve cognitive rehabilitation outcomes.

The overall goal of this project is to advance a biologically-based approach to treatment of reading disorders after stroke, which will expand the limits of cognitive rehabilitation. Using a novel brain imaging technique, called real-time functional magnetic resonance imaging (fMRI) neurofeedback combined with right hand motor imagery, this project will re-instate brain activity in the left language-dominant hemisphere. Stroke patients will practice modulating their own brain activity using fMRI neurofeedback signal and will select the most effective mental strategies that help them maintain brain activation patterns associated with better reading recovery.