Award Title: Does dose-controlled brain stimulation enhance motor rehabilitation in chronic stroke patients?
Funder: Dunhill Medical Trust

Abstract: Stroke is a leading cause of disability among older people. Around three quarters of stroke survivors are left with difficulties moving a limb, which has a profound effect on independence. The need to find effective treatments to promote recovery and independence after stroke is increasingly important, both because the number of older people in the population is increasing, and because more people are surviving stroke. In small studies, non-invasive brain stimulation, such as transcranial direct current stimulation, can promote rehabilitation after stroke(3,17–21), by enhancing motor learning(6,7,25–30). However the effects are variable and so tDCS has not yet made the transition to use in clinical practice(6,7). Some of this variability is likely due to individual differences in how much current enters the brain and where it goes(9). Recent work on current flow modelling has enabled the question of 'how much' and 'where' to be accurately estimated for the passage of electrical current into an individual's brain(8,31,32).

In this project, we will use current flow modelling to create individualised, optimised tDCS interventions with higher reliability and efficacy than traditional approaches.

Firstly, we will assess the validity of current flow models in chronic stroke patients using diffusion tensor magnetic resonance electrical impedance tomography (DT-MREIT), an MRI technique that measures the pattern of current flow through the brain(11,33,34). Current flow inside the healthy brain can be predicted with high precision using current flow models(35), however, there is currently no empirical data about how lesioned tissue may influence current flow. This insight into how such lesions might distort or alter current flow would be hugely beneficial for validating current flow models, and allowing the design of optimised, dose-controlled tDCS delivery in stroke patients.

The second and third studies will compare the effects of optimised, dose-controlled tDCS with conventional tDCS application in chronic stroke patients. We will quantify how optimisation increases overall beneficial effects, and reduces inter- and intra-individual variability, in physiological (study-2) and motor learning (study-3) measures.

In study 2 we will examine the neurophysiological changes induced by tDCS to primary motor (M1) and sensory cortices (S1), thought to be associated with positive rehabilitation outcomes(36).

Study 3 will assess the effects of tDCS protocol on upper-limb motor learning, a key process for recovery of motor function. This will provide crucial insight into how the application of tDCS can be made more effective in patient populations such as stroke.

Lay Abstract: Recent research has shown the benefit of combining physiotherapy with a form of non-invasive brain stimulation known as transcranial direct current stimulation, or tDCS. This technique involves placing two electrodes on the participants’ scalp and passing a small, barely perceptible electric current through the brain. Patients who are given tDCS while undergoing rehabilitation tend to show greater improvements in movement control than those who do not.

However the effects of tDCS can be very different across individuals. This is likely due to differences in the shape of individuals' head causing variations in how much current actually enters the brain and where this current actually flows. These differences are even greater in individuals with stroke, as the damaged brain tissue can distort the path of current flow. In other words, there is currently no established and validated way to control the effective dose of the treatment.

However, the amount of current, and the path it takes through an individual's brain, can be estimated using a technique known as current flow modelling. In this set of studies we plan to investigate how adjusting tDCS settings on the basis of individual differences in current flow can enhance the beneficial effects of tDCS on upper-limb stroke rehabilitation. We will use a novel MRI technique, called diffusion tensor magnetic resonance electrical impedance tomography (DT-MREIT) that can measure the actual flow of current though the brain of chronic stroke survivors with tDCS. We will use this to assess the accuracy of our current flow models applied to stroke patients with different lesion locations and sizes. This is an essential requirement for delivering precise stimulation to an individual's brain.

We will then create optimised tDCS treatments where the amount of current entering the brain, and which parts of the brain it affects, are the same in all patients. In our subsequent studies we will assess whether our optimised tDCS treatments results in less variability, and greater positive effects on motor rehabilitation and measures of brain activity. We predict that tDCS optimised for each individual will enable it to have a positive effect in all stroke patients. This work will provide crucial validation that tDCS can be made more effective in patient populations suffering from age related diseases such as stroke.

Research Activity Codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health Categories: STROKE;NEUROLOGICAL