Stimulating language recovery after stroke: Tailored non-invasive electrical stimulation of the domain-general frontoparietal network.

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Context There are 1.2 million stroke survivors in the UK with a societal cost of £26 billion a year. Language impairment (aphasia) is a major cause of disability after stroke affecting a third of all patients. Current therapeutic strategies for treating aphasia have either had little success or demand prolonged and intensive speech and language therapy which is not feasible within the NHS. Most of these therapeutic strategies have largely focused on improving the residual language-specific processes or brain regions that support them. However, I have shown that residual language function after stroke is also dependent on support from the so-called domain-general brain regions that mediate general cognitive processes such as attention, working memory, and learning (or reacquisition) of a skill. Importantly, increased activity within the domain-general regions of a well-established bilateral frontoparietal brain network (FPN) has been shown to be associated with better recovery of language function after stroke, building a case for its potential as a prognostic biomarker and therapeutic target. The overall aim of this proposal is to investigate and to optimise the compensatory role of this domain-general brain network in recovery of language function after stroke. Objectives1. To use a rapid real-time brain imaging protocol to measure the function of the domain-general FPN across a wide range of language and non-language tasks in patients after stroke. Based on preliminary results, it is expected that patients who have a similar FPN function compared to the controls, will have the best language outcomes following their stroke. Conversely, those patients with a dissimilar FPN functional profile to the controls will have the worse outcomes.2. To combine real-time brain imaging and non-invasive brain stimulation to rapidly identify personalised brain stimulation settings that maximise the function of the domain-general FPN for each individual patient.3. To investigate whether the use of personalised brain stimulation of the domain-general FPN improves behavioural performances in patients after stroke. MethodI will use advanced magnetic resonance imaging (MRI) to study brain structure and function. Importantly I will use a novel technique that analyses brain function in real-time whilst participants perform tasks in the scanner. This will allow for a rapid assessment of the function of domain-general brain regions of the FPN across a wide range of experimental conditions. I have used this technique in a pilot study of patients to show that the pattern of activity of the FPN across a range of language and non-language tasks, is related to the degree of language impairment after stroke. I will use the same technique on a group of 50 patients following a stroke, and relate their imaging measures to their language function after the stroke. In a second study, I will use the same real-time brain imaging technique combined with non-invasive brain stimulation, to identify for each individual patient the optimal brain stimulation settings that maximally activate their domain-general FPN. Here, the optimal phase and frequency of the brain stimulation will be identified for each individual patient. In the third study, I will apply brain stimulation using the personalised stimulation settings for each patient, to improve behavioural performances.Potential applications and benefitsLanguage impairment after stroke is common, and it is unclear how best to rehabilitate individuals. Identifying individuals who will benefit from rehabilitation of domain-general brain regions that support their residual language function will provide a new therapeutic avenue. Demonstration of modulation of these regions using a personalised non-invasive brain simulation will not only benefit patients with language impairment, but will have far reaching implications for rehabilitation across a wide range of brain deficits and injuries.