image: Tiny changes in the microscopic structure of the human brain may affect how patients respond to an emerging therapy for neurological problems. view more
Credit: Lucia Li et al. 2019
Tiny changes in the microscopic structure of the human brain may affect how patients respond to an emerging therapy for neurological problems.
The technique, called non-invasive electrical brain stimulation, involves applying an electrical current to the surface of a patient's head to stimulate brain cells, altering the patient's brain activity. It is being trialled for a range of neurological problems including recovery from stroke, traumatic brain injury, dementia, and depression, but research to date has found the effects to be inconsistent
Now, a team led by researchers at Imperial College London has shed more light on why these inconsistencies occur and may provide physical evidence for why some patients respond better than others - because of the fine structure of their brain tissue. The new research suggests it may be possible to target the therapy to those patients most likely to benefit.
They found that differences in the makeup of the brain's white matter - the tissue deep in the brain and rich in the branching 'tails' of nerve cells - were key. The research revealed that those who had more connectivity in the regions being stimulated were more likely to respond better to the treatment.
According to the team, the findings, published in the journal Brain, could help to personalise the non-invasive electrical brain stimulation, targeting the treatment to patients who are most likely to gain clinical benefits.
Dr Lucia Li, a clinical lecturer in neurology in the Department of Brain Sciences at Imperial College London, and lead author of the study, said: "With all the current buzz around brain stimulation for altering brain activity, it's important to understand who will benefit most from this technique in the clinic.
"Problems with white matter structure are a feature of a range of different neurological conditions. Our study is a step towards more personalised use of brain stimulation, which will improve the outcomes using this technique, as well as reduce the number of people treated un-necessarily."
In the study, researchers looked at 24 healthy patients and 35 patients recovering from a moderate or severe traumatic brain injury (TBI). Participants performed a task inside an MRI scanner (see 'The Stop Signal Task' in notes to editors) while receiving small amounts of electrical current through electrodes on the surface of the scalp or a placebo. They were unable to tell whether they were receiving brain stimulation or not.
They found that healthy participants who received brain stimulation performed better in the task than when they didn't receive the treatment. For patient with TBI, task performance in response to stimulation varied widely.
However, when they analysed MRI scans, they found that those participants with highly-connected white matter in the brain region being stimulated responded best to the treatment, and those who had damaged or less-connected regions of white matter showed less improvement.
They also found that brain stimulation could partially reverse some of the abnormalities in brain activity caused by TBI.
The team cautions that while more work is needed to confirm the findings, it could mean brain stimulation might prove a useful treatment approach for other neurological conditions with abnormal brain activity as a feature, such as dementia.
"We found that people with stronger white matter connections in their brain had better improvement with stimulation," Dr Li explained. "This might be an important reason why previous studies have found that some people benefit from stimulation, whilst others don't and means we can start using brain stimulation in a more personalised way."
According to the researchers, the study is limited in that in that they only investigated one type of cognitive behaviour and would need to be replicated in other types of behaviour to show if the findings apply more generally. In addition, they only stimulated one region of the brain, so they don't know whether the effects are specific to this region, or whether other regions can be stimulated.
Dr Li explains the team will now focus on larger studies with more participants to investigate what other factors influence someone's response to brain stimulation. They will also apply the technique to other conditions with abnormalities in brain activity to see if they can alter activity and improve brain function.
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The work was supported by the Wellcome Trust and the National Institute for Health Research. Patients were predominantly recruited from St Mary's Hospital (Imperial College Healthcare NHS Trust) and imaged at the Imperial College Clinical Imaging Facility.
'Traumatic axonal injury influences the cognitive effect of non-invasive brain stimulation' by Lucia Li et al. is published in the journal Brain.
Notes to editors
1. Imperial College London is one of the world's leading universities. The College's 17,000 students and 8,000 staff are expanding the frontiers of knowledge in science, medicine, engineering and business, and translating their discoveries into benefits for our society.
Imperial is the UK's most international university, according to Times Higher Education, with academic ties to more than 150 countries. Reuters named the College as the UK's most innovative university because of its exceptional entrepreneurial culture and ties to industry.
2. The Stop Signal Task
In this study patients had to perform the Stop Signal Task (SST), which is almost like a visual version of the children's game 'Simon says'.
Participants hold controls in either hand and have to press a button on the correct controller in response to an arrow pointing left or right (left for left, right for right).
But, every now and again, a red dot appears over one of the arrows. This dot is the 'stop' signal, so players have to abort the action and avoid pressing the button as they would normally.
The main outcome of the game is to measure the stop signal reaction time (SSRT). This measure accounts for an individual's motor reaction time - the time for between their brain seeing and processing the signal and triggering the correct action.
It is calculated as [Mean Reaction Time - Stop Signal Delay], where stop signal delay (SSD) is the interval between when the participant first sees the arrows and the appearance of the 'stop' signal which produced successful stopping on 50% of 'stop' trials. A low SSRT indicates good task performance, indicating that little time is required for the participant to abort a prepared motor response.
Journal
Brain