Enhancing the effectiveness of brain stimulation for stroke recovery

Overview

Haya Akkad was awarded a Brain Research UK PhD studentship in 2019 to enable her to pursue research aimed at improving recovery in stroke survivors.  

Following successful completion of an ambitious programme of work focused on the advancement of electrical brain stimulation for post-stroke recovery, she was awarded her PhD from UCL in 2024.

Background

The number of deaths from stroke continues to decrease, thanks to innovations in emergency treatment and care, along with improving public awareness of the signs of stroke and the need for urgent medical attention. Whilst this is cause for celebration, investment in rehabilitation has unfortunately not kept pace and many survivors are left with severe disabilities. Two of the most common and debilitating problems are limb weakness and language and communication problems: 

• More than three quarters of stroke survivors report arm weakness. This makes it difficult to carry out daily living activities and threatens people's independence.
• A third of stroke survivors have aphasia, which affects the ability to speak and understand what others say. It can also affect the ability to read and write. It is profoundly frustrating for those affected, often leading to social withdrawal and a higher risk of depression.

Traditional post-stroke rehabilitation techniques to overcome such problems typically require intensive programmes delivering at least 100 hours of treatment. This is rarely available as standard clinical care, meaning that many patients simply do not recover good function. There is a pressing clinical need to develop economically feasible ways to boost the effects of rehab and facilitate a better recovery.  

Read more: About stroke

Enhancing the effectiveness of brain stimulation for brain repair

Stroke and other brain injuries can disrupt vital connections between different parts of the brain. These connections, or 'neural networks', usually interact to give rise to particular functions and their disruption underlies some of the disabilities seen in stroke.

Non-invasive brain stimulation (NIBS) is becoming widely used as a tool to promote recovery of the brain after injury. It involves the delivery of electrical current to the brain via electrodes or a magnetic coil placed on the head, with the aim of 'resetting' the disrupted neural networks.

The use of NIBS has shown some promising results in stroke patients, but a lack of understanding of precisely how and why it works has meant that effects have been inconsistent across studies and between patients, hindering its wider application.

A better understanding of the mechanisms involved will inform better decisions about precisely which part of the brain to target, what dose is required, and how to deliver that dose to the target area. This is key to improving effectiveness.

Haya set out to address this in her PhD research, working with supervisors Professor Jenny Crinion and Professor Sven Bestmann, who bring a wealth of experience in neurorehabilitation, speech and language therapy, brain stimulation and neuro-imaging.

She focused on the two most common post-stroke symptoms - severe word-retrieval deficits (anomia) and one-sided upper limb weakness (hemiparesis) - and pulled together evidence about behaviour, brain structure and brain function to provide new insight as to why current NIBS approaches can fail, and how they can be improved.

Starting with an extensive literature review and progressing to deliver three major experimental studies, Haya demonstrated that the most common brain regions targeted with NIBS for post-stroke anomia and upper limb hemiparesis are not the regions that most commonly drive these deficits, and thus may not be the most suitable targets. This sheds light on the low effectiveness of current NIBS interventions for post-stroke recovery.

From this, Haya proposed revised, evidence-based approaches for consideration in future trials and designed detailed brain stimulation protocols, tailored to the relevant brain network. These offer a roadmap for future clinical trials that can potentially provide more effective brain-targeted treatments and improve outcomes for stroke survivors.

Impact

Stroke represents a significant burden on individuals, healthcare systems and society as a whole. Two-thirds of stroke patients leave in-patient hospital care with a disability^[i], requiring ongoing rehabilitation and care, and the NHS does not have the resource to deliver this at the levels required.

Non-invasive brain stimulation has shown promising results, with the potential to facilitate substantial recovery in some stroke patients. It is cost-effective and highly scalable. Effects are inconsistent across studies, however, and highly variable between patients, and this has hindered translation to the clinic.

Haya’s PhD research addressed these challenges, providing new insight to the efficacy of current NIBS interventions, and setting out a revised approach based on mechanistic principles. Explored within the scope of two common post-stroke deficits – anomia and upper-limb hemiparesis – this work offers a roadmap for future clinical trials, potentially leading to improved outcomes for stroke survivors.

The impact of this work extends beyond immediate clinical applications. It challenges existing NIBS paradigms and emphasises the importance of considering network-level effects in the design of brain stimulation protocols. The methodological approach has relevance beyond stroke, for the treatment of other types of brain injury or neurological impairment.

Equally important, this PhD studentship has supported the career development of a talented researcher. It enabled Haya to work with world-leading experts at both UCL and Harvard University, thanks to an additional fellowship she secured during the course of her PhD. This has equipped her with a versatile and advanced skill set, which she is now applying in her role as a Post-doctoral research fellow in the Department of Clinical and Experimental Epilepsy at UCL Queen Square Institute of Neurology. In this new role she is building on the work carried out during her PhD and expanding it to the treatment of neurological disorders beyond stroke. She continues to collaborate with her PhD supervisor Professor Jenny Crinion to apply her PhD work for the benefit of stroke survivors, as well as with Dr Mike Fox at Harvard on the methods of brain network mapping.  

Key publications

Akkad, H, Hope, TMH, Ondobaka, S, Duncan, J, Leff, AP,Crinion, J (2023). Mapping spoken language and cognitive deficits inpost-stroke aphasia. Neuroimage: Clinical. doi 10.1016/j.nicl.2023.103452

‍Akkad, H, Dupont-Hadwen, J, Bestmann, S, Stagg, CJ (2021). Increasing motor skill acquisition by driving theta-gamma coupling. eLife. doi 10.7554/eLife.67355.

‍‍Hope, TMH., Ondobaka, S., Akkad,H., Nardo, D., Pappa, K., Price, CJ., Leff, AP., Crinion, J. (2024). Predicting online behavioural responses to transcranial direct current stimulation in stroke. Life. doi 10.3390/life14030331

Hope T, Nardo D, Holland R, Ondobaka S, Akkad H, Price C, Leff A, Crinion J (2021). Lesion site and therapy time predict responses to a therapy for anomia after stroke: a prognostic model development study. Nature Scientific Reports. doi 10.1038/s41598-021-97916-x

 

‍_{[i] StrokeAudit 2015: https://www.strokeaudit.org/getattachment/AnnualReport/Historical-Guideline/Apr2014Mar2015-AnnualReport.pdf.aspx}