Early adversity and the brain: Bangladeshi children may provide lessons

neuroimaging adversity Bangladesh
Children from the neighborhood around the neuroimaging lab

Dhaka, Bangladesh, is a megacity, one of the world’s fastest growing. By 2025, the U.N. predicts, Dhaka will be home to more than 20 million people as rural migrants swell its population. Many residents live in extreme poverty, crowded into dense, hot, chaotic slums with open sewers and corrugated housing.

While traditional global health programs have focused on curbing infectious disease, low-resource settings like Dhaka are also coming to be seen as “living laboratories” for investigating how adversity affects children’s brain development. Last year, the Bill & Melinda Gates Foundation awarded a two-year, $2.5 million grant to Charles Nelson, PhD, to bring the first fully equipped neuroimaging facility to Bangladesh.

Nelson, head of the Laboratories of Cognitive Neuroscience at Boston Children’s Hospital, has spent 15 years studying the cognitive and behavioral effects of adversity in severely neglected, institutionalized Romanian children. The majority of children in the slums of Dhaka live with their families, but they face multiple other challenges to brain development: malnourishment, lack of access to clean water, exposure to environmental toxins, poor sanitation, maternal depression and low parental education.

“We are collecting information on all the forms of adversity to figure out which are the biggest issues,” says Nelson.

And there are plenty of volunteer families within easy walking distance of the lab.

Sustainable neuroscience

Up and running since March, the neuroimaging lab is housed under the umbrella of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b). The research team—comprised of local medical officers and field researchers trained by Nelson and colleagues—is drawing subjects from a large vaccine study called PROVIDE, housed in the same building.

Neuroimaging clinic Bangladesh
The neuroimaging lab is housed in the apartment building at left.

The initial goal is to create a test battery that can be implemented in low-income countries to evaluate brain and cognitive function in children’s first few years of life. The ultimate goal is to create interventions to help children develop optimally and then use these test tools to evaluate their efficacy.

Testing for 6- and 36-month-old children includes EEG studies to record brain electrical activity (below left), eye-tracking studies to monitor social engagement and near-infrared spectroscopy (NIRS) (below right) to monitor oxygen use in the brain, as well as detailed cognitive and behavioral assessments.

Bangladesh brain researchNIRS cropped

 

In a separate facility, 2- to 3-month-old infants are undergoing MRI neuroimaging studies to look for structural differences in their brains. In all, the team plans to test about 300 children over a two-year period, offering meals for the entire family as an incentive for the clinic visits. (Through the larger PROVIDE study, families also receive continued primary medical care.)

Such studies have never before been done in Bangladesh, and when program managers Alissa Westerlund and Swapna Kumar made a site visit in November to scope out the conditions, they wondered whether they’d be able to open the lab.

Dhaka Bangladesh PROVIDE neuroimaging
The road where the neuroimaging lab is located in November 2014, before repairs were made.

The building had no grounded electricity and not enough electrical outlets. Equipment would need to be brought in over a bumpy, dusty road. A huge hole gaped in the road near the clinic from some construction that was never completed. But the collaborating icddr,b team completed their list of fixes on schedule, and the equipment was shipped and installed in March.

Local control

The tests and assessments are all carried out by Bangladeshi medical officers and field researchers. Two of the researchers came to Boston for three weeks of training, and Nelson and colleagues trained an additional eight field researchers and medical officers on the ground in Dhaka.

The training wasn’t just technical but also included tutoring in techniques Boston Children’s researchers routinely use to engage the children and their mothers. Those techniques include communicating exhaustively with mothers about the goals of the research, playing with the children and motivating them to take part in the cognitive tests—time-intensive “niceties” that at first seemed foreign to the local research team.

“They’re not used to having to keep the child happy during the entire task,” says Westerlund. “We’re teaching ‘baby whispering’—when to blow bubbles, when to stop the session.”

brain research Dhaka Bangladesh

Baby MRIs

The local team has also been taught how to do brain MRIs in sleeping babies without having to sedate them, using a protocol developed by Nadine Gaab, PhD, and Ellen Grant, MD, at Boston Children’s. Mothers keep their infants awake on the trip over to the clinic, then are brought to a dark, soothing room where they feed and soothe the infant to sleep. Before being slipped into the scanner, the sleeping babies are exposed to the MRI sounds, so they can get used to the noise and don’t startle awake once in the scanner. The protocol also includes MRI-safe swaddle sacks donated by Halo, secured with Velcro instead of metal zippers.

The first baby goes into the MRI scanner at Dhaka’s National Institute of Neurosciences Hospital. The local team is led by radiologist Nazrul Islam (left) with Boston-Children’s-trained MRI technicians (left) and medical officers (right). Danielle Sliva from the Gaab Lab at Boston Children’s (right rear) oversaw the field training and pilot testing. The baby’s mother is third from the right.
The first baby goes into the MRI scanner at Dhaka’s National Institute of Neurosciences Hospital. The local team is led by radiologist Nazrul Islam (far left) with Boston-Children’s-trained MRI technicians (left) and medical officers (right). Danielle Sliva from the Gaab Lab at Boston Children’s (right rear) oversaw the field training and pilot testing. The baby’s mother is third from the right.

In the pilot study, two babies have had successful MRIs (a third woke up in the scanner), and 40 older children have been tested with EEG, eye-tracking and/or NIRS. In the full study, the team plans to study 25 to 30 children per month, reaching their target of 300 children by the second half of 2016.

Nelson plans to report the pilot data in October at a Gates Foundation meeting in Beijing. In keeping with his findings in Romania, he expects that the greater the adversity a child is exposed to, the greater the effect on the brain—including notably smaller brains, less brain electrical activity and altered patterns of connectivity. Once a sustainable test battery is established, the Gates Foundation plans to launch similar clinics in other low-resource countries.

“The idea was, ‘can we do this, and in a way that it could be mobile?’” says Nelson. “We also want to intervene to ameliorate the effects of adversity and use our measures to see what changes have occurred in the brain. This area of research is so new that it’s really an opportunity for us to step up and figure out the best approach.”