Imaging

 Scanning cerebral damage in malnourished children 

For years, behavioural tests have been used to chart brain development in children. However, current tests may not be fit for purpose in poorer countries. A new portable brain scanning technique is now being used in The Gambia to more accurately gauge children’s neural development. Abi Millar finds out more. 

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uring the first few years of life, a child’s brain undergoes an extraordinary process of development. Forming more than a million new neural connections every second, the brain is more flexible and sensitive at this point of life than it’ll ever be again.

For better or worse, this extreme plasticity means the child’s environment is critical. A child growing up in a healthy, safe environment is far more likely to hit the expected developmental milestones. Conversely, if a child is exposed to chronic stress, that will shape the structure and subsequent function of the brain.

Unfortunately, early-life stress is a broad category, comprising everything from maltreatment and neglect to poverty. As a growing body of research has demonstrated, growing up poor can profoundly affect a person’s cognitive development. It is even associated with less complexity in certain regions of the brain.

However, much remains unknown, particularly when it comes to children living in lower-income countries. As Clare Elwell, a professor of medical physics at University College London, explains, there are major gaps in the scientific literature.

“There are modelling studies to suggest one third of children living in resource-poor settings fail to reach developmental milestones, but many of the tests have been applied once the children are slightly older or even reaching school age,” she says. “Very little is known about what’s driving those differences in brain development in the early stages of life.”

 The gaps in our knowledge

Much of the research on the topic comes from a 2016 study in PLoS Medicine. Almost 100,000 children living in 35 lower-income countries were tested between 2005 and 2015. A third of them had failed to develop a core set of age-appropriate skills, including 44% of those in sub-Saharan Africa.

What this study makes clear is that poverty has a corrosive impact on brain function. Since a quarter of children worldwide are undernourished before they reach the age of five, there is no doubt that these problems are far-reaching.

What it doesn’t show, however, is how the problems occur in the first place. Since the children tested were three or four years old, it can’t tell us much about that early, crucial stage when so many neural connections are being formed.

By default, you can’t use behavioural assessments until there’s actually observable behaviour.

“By default, you can’t use behavioural assessments until there’s actually observable behaviour,” says Elwell. “Most of the tests are not particularly useful in the first few months of life, even though that’s often when you want to understand what trajectory the infants are on.”

There’s a further problem with behavioural assessments, in that they may not be very reliable. Since the tests were developed in higher-income countries (particularly in the US and Europe), they aren’t always fit for purpose in other populations.

“For example, one of the tests involves an assessment of the infants’ motor function – how well they can move and get around,” says Elwell. “One of the assessments is to see whether an infant can climb stairs. But in many lower-income settings there may not be any stairs for the infant to climb, so they may not develop that skill.”

On the other hand, a child in sub-Saharan Africa might be very good at clinging onto their mother’s back while she wraps a shawl around them. This is not something a child in the US or UK would score well at.

“The cultural translation of these tests is not always particularly good, which means making comparisons between different populations is hard,” says Elwell.

 The BRIGHT Project

It was for this reason that Elwell, along with a multidisciplinary team of researchers, initiated the Brain Imaging for Global Health (BRIGHT) Project. A longitudinal study of infants in the first 24 months of life, the project is the first to provide neuroimaging of children in Africa.

It is led by researchers at UCL, Birkbeck University London, the Medical Research Council Units in The Gambia and Cambridge, and Cambridge University Hospitals, and has received funding from the Bill & Melinda Gates Foundation.

“Infants are recruited antenatally and then followed up to their second birthday,” says Elwell. “We’re using brain imaging along with a whole catalogue of infant development tests to develop a brain-function-for-age curve. This will help us understand the trajectory of the infant’s brain development.”

Infants are recruited antenatally and then followed up to their second birthday.

The five-year study, inaugurated in May 2015, is following 200 infants in The Gambia along with 60 in the UK. Accompanied by parallel studies in Bangladesh and India, the project will enable atypical brain development to be flagged up at the earliest stage.

“We’re using the same assessments for both those cohorts, so it gives us an understanding of how the infants are developing,” says Elwell. “That in turn will help us understand more about what type of interventions would be most appropriate at which age group, whether nutritional or otherwise.”

For instance, it may be possible to see exactly how a particular nutritional deficiency affects the brain. This could guide the design of a targeted intervention, in which a group of infants (or their mothers) are given supplements.

 The imaging technique

What makes the BRIGHT Project possible is a new neuroimaging technique called functional near infrared spectroscopy (fNIRS). Portable, inexpensive and easy to set up, the technique does not require the child to remain still, and can therefore be used right from the moment of birth.

A headband is placed on the subject’s head, and infrared light is passed through the skull to determine the colour of the blood. By looking at the distribution of red blood, which is oxygenated, it is possible to map activity in any given region of the brain.

By looking at the distribution of red blood it is possible to map activity in any given region of the brain.

Each child in the BRIGHT project is tested on six occasions – at one, five, eight, 12, 18 and 24 months old. In each case, they will be exposed to culturally appropriate stimuli, such as videos of Gambian adults talking and moving.

As well as being suited to rural settings, this technique can be quite specific when it comes to identifying abnormalities. For instance, it has previously been used to identify early biomarkers of autism. It will therefore enable researchers to target their interventions with some precision.

“We believe that fNIRS provides an essential bridge between our current understanding of cortical activity in the developing brain and our knowledge of adult human brain function,” wrote BRIGHT researchers, in 2014 pilot study published in Nature.

Once the study is completed, the researchers will have a wealth of new information at their disposal. With the end date slated as December 2019, they will be soon able to design interventions armed with insights into how poverty can affect the growing brain.