Meet our researchers: Professor Sven Bestmann, UCL Institute of Neurology

When and how should we apply brain stimulation to help recovery after stroke?


Professor Sven Bestmann was awarded a Brain Research UK project grant in September 2017 for his work on non-invasive brain stimulation for promoting recovery after stroke.

Better awareness and improved treatment have both contributed to a reduction in mortality from stroke. But many survivors are left with disabilities that limit their ability to live productive, independent lives.

Electrical brain stimulation is becoming widely used as a tool to promote recovery of the brain after injury. Results are mixed, however, and this is partly due to the fact that it has not been possible to tell whether the stimulation is reaching the intended parts of the brain. Professor Bestmann will address this using cutting edge mathematical and brain imaging techniques to make sure that the right amount of electrical current is delivered to the right part of the brain, helping to unlock the full potential of brain stimulation to promote recovery after stroke.

Following rigorous assessment as part of our competitive project grant round, this project was selected for funding under our ‘acquired brain damage’ theme because the members of our Scientific Advisory Panel felt that it would make an important contribution to knowledge in an important area, with high unmet need. With clear research questions, and a simple design, the panel were confident that the research team would succeed in answering these important questions about the use of non-invasive brain stimulation.


About stroke

A stroke occurs when the blood supply to part of the brain is cut off. This starves the brain of oxygen and can have devastating consequences.

The number of UK deaths from strokes is less than half what is was 30 years ago. This decrease is in part due to a reduction in the incidence of strokes over the same period, but also to a greater awareness of symptoms - meaning that help is sought sooner - and availability of better treatments such as clot-busting drugs.

The lower mortality rates mean that more people are surviving stroke than ever before and it is estimated that there are 1.2 million stroke survivors in the UK today.

Over half of all stroke survivors are left with a life-limiting disability. This may include problems with limb weakness, impaired mobility, or problems with speech, balance and co-ordination.

In addition to the huge personal impact on the lives of survivors, the impact on society is enormous. The economic burden of stroke in the UK is estimated at £9 billion a year – including health and social care costs, informal care, productivity losses and benefit payments. Two-thirds of working age survivors are unable to return to work.

Improving stroke recovery is therefore a key goal.

Read more: Stroke


Brain stimulation to promote recovery after stroke

Improving stroke recovery is a crucial clinical and scientific goal but our healthcare systems struggle to deliver enough rehabilitation in the timeframe required.

Non-invasive brain stimulation is an exciting tool that may help to increase the effectiveness of rehabilitation after stroke. It involves the delivery of a small electrical current to the brain using a pair of electrodes placed on the head. There is a large body of evidence gathered from animal models of stroke that this may increase the capacity of the brain to recover from the kind of injury caused by stroke, and boost the effects of behavioural training such as physiotherapy.

The technique is widely used in the design of clinical trials but there are a number of key mechanistic questions that have not yet been answered, meaning that the trials have no mechanistic rationale and are therefore unlikely to succeed.

In simple terms, we currently do not know when and how best to apply brain stimulation in order to assist behavioural training.

•    When should brain stimulation be applied? Is it best early or late after stroke? Is it more effective within the first few weeks or several months afterwards? We know that the brain responds to early rehabilitation and therapy differently than it does to later similar input, but no systematic study exists to tell us when brain stimulation works best.

•    How should brain stimulation be applied? The effects of brain stimulation are variable and this is partly due to the fact that we don’t know which brain regions are being stimulated, or how much electrical current is actually delivered. This has likely contributed to the overall ineffective use of brain stimulation. Recent developments now allow better control over the amount of current that is delivered to the brain, and the team will exploit these developments to determine how the effects of brain stimulation are influenced by the time since stroke.

In this study, Professor Bestmann and colleagues will recruit two groups of first-time stroke patients who have impaired use of an arm and hand: i) ‘early’ patients, between 2 and 6 weeks post-stroke; and ii) ‘late’ patients, more than six months post-stroke.

They will apply non-invasive brain stimulation in a dose-controlled manner, to ensure that the dose of stimulation to the brain is the same in all patients. They can then compare the effects in the different groups of patients.

Their approach ensures that the same dose of electrical current gets to the same target brain area in all patients. This means that any differences in response to brain stimulation between the two groups can be attributed to how long ago the stroke occurred.


About the research team

Professor Bestmann has a long-standing track record in neuro-stimulation, human electrophysiology and movement control. He has pioneered several approaches for studying the impact of non-invasive brain stimulation on the brain.

He is working with Professor Nick Ward, a neurologist at the National Hospital for Neurology and Neurosurgery in London. Professor Ward directs the Upper Limb Neurorehabilitation Programme, the only dedicated clinic for stroke patients with upper limb impairment in the UK. The ‘late’ patients will be recruited from this clinic, which sees 220 patients annually.


Impact

If non-invasive brain stimulation does not appear to work, one explanation is that the electrical current simply missed the target, but there has previously been no way of knowing if this is the case. This has prevented attempts to test whether non-invasive brain stimulation could help stroke survivors by increasing the effectiveness of physiotherapy, for example.

This project will establish whether reliable and predictable changes in brain function can indeed be triggered by targeted brain stimulation, if dose-controlled delivery is applied. It will provide, for the first time, the basic understanding and insight for designing clinical trials to test the efficacy of brain stimulation for enhancing rehabilitation after stroke, both in the first few weeks as well as years after. In other words, this work will allow us to determine the ‘who, how and when’ of non-invasive brain stimulation for promoting recovery after stroke. It will underpin future trials examining the therapeutic potential of non-invasive brain stimulation.

“The use of non-invasive brain stimulation techniques for neurological rehabilitation has generated enormous interest in recent years. While such techniques might hold significant potential to improve rehabilitation, so far results have been disappointing. As the Investigators point out, this is likely the result of limited understanding of the biological effects of the techniques, the influence of brain states at the time of stimulation, and a “one size fits all” approach to stimulation. The proposed project will address these important issues in a stroke population and should provide important and novel insights.

“Without studies such as this, the field of therapeutic brain stimulation will continue to be characterised by studies lacking strong scientific rationale and result in more wasted research effort.” External reviewer

 

Related research projects

Acquired brain and spinal cord injury - which includes stroke - is one of our current priority research areas, reflecting the large unmet need in this area. Other research projects currently funded under this theme include: