Saturday, May 17, 2025
5/17/2025
Precision Neuromodulation in Post-Stroke Aphasia - Stroke is a leading cause of disability, often resulting in long-term cognitive impairments. One of the most common and devastating disabilities from stroke is impairment of the ability to communicate with language, or aphasia, which often leads to loss of employment, social isolation and depression in stroke survivors with aphasia (SWA). Current aphasia rehabilitation approaches yield only modest results. There is a great need to develop more effective strategies to improve language recovery and quality of life for SWA. The long-term goal of proposed research is to enhance generalization outcomes from a linguistically-motivated therapy—semantic feature analysis (SFA) therapy—using excitatory theta burst stimulation (TBS), which is a reliable and stable form of repetitive transcranial magnetic stimulation. SFA on its own is shown to promote generalization in improving word-finding in SWA, though gains achieved on untrained (or new) stimuli are typically small. The overarching hypothesis of our work is that SFA given during the post-TBS period will benefit from the heightened state of neural excitability, leading to more extensive therapy-relevant neuroplasticity and generalization. But the biggest unanswered question for excitatory TBS is how to select the best stimulation site to achieve the strongest treatment effect. A previous approach uses fMRI prior to therapy (baseline) to identify the brain region showing the strongest level of activity during a language task. However, a major weakness of this approach is the assumption that the sites exhibiting maximal activation at baseline are the same sites where maximal neuroplasticity can be achieved through therapy. Another weakness is that it assumes that maximal fMRI activation reflects a causal link with behavior. We aim to solve these problems by implementing a novel multimodal approach to TBS site selection. We will select a precision site that 1) shows fMRI evidence of changes in activation over an initial 2 weeks of SFA, and 2) shows evidence of a causal contribution to word retrieval abilities using inhibitory TBS. In Aim 1, we will establish for the first time a causal contribution of neural correlates of SFA therapy to language performance using inhibitory TBS. In Aim 2, we will determine the extent of generalization with SFA combined with excitatory TBS given to the precision site. Our primary outcome measure will be changes in accuracy of untrained stimuli and secondary measures will evaluate changes in patient- reported communication abilities. In Aim 3, we will explore changes in neural activation after SFA with excitatory TBS and neural correlates of generalization. This project is highly innovative and will be the first study to combine excitatory TBS with SFA to improve generalization in SWA using a precision targeting approach. At this stage, a high-risk, high-reward R21 study will generate critical preliminary data to determine whether a larger-scale clinical trial is warranted to evaluate the effectiveness of excitatory TBS with SFA. The current project promises to pave the way to achieve Level A clinical recommendation (definite efficacy) for excitatory TBS, which will be a major clinically meaningful breakthrough for the field of post-stroke aphasia recovery.
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