The vast portion of the African continent that lies south of the Sahara desert—sub-Saharan Africa—is home to 1 billion of Africa’s 1.3 billion people. It has one of the most dynamic of the world’s populations, expected by the U.N. to double in size by 2050, with 40% currently under the age of 15.

Sub-Saharan Africa has the highest proportion of children at risk of developmental delay worldwide—66% of those under age 5, research indicates—reflecting the fact that nations in the region are among the world’s most socio-economically challenged. Despite this fact, says a South African-based research team led by a BBRF grantee, “there is very limited neuroimaging research” focusing on the neurobiological factors underlying developmental delays—not only in Africa but in affluent nations that conduct the bulk of global neuroscience research.

Kirsten Donald, M.D., Ph.D., of the University of Cape Town, received a BBRF Independent Investigator grant in 2016 to perform imaging studies of infants whose mothers had suffered depression. In a study published recently in the journal NeuroImage, Dr. Donald and a team that included Dan Stein, Ph.D., a 1991 BBRF Young Investigator, and Katherine Narr, Ph.D., a 2003 BBRF Young Investigator, reported that they had successfully tested a procedure for obtaining high-quality multi-dimensional neuroimaging and cognitive data for children early in life—ages 2-3. The paper’s first author was Catherine Wedderburn, MBChB, of the London School of Hygiene & Tropical Medicine.

The paucity of neuroimaging data for children of this age motivated the team, which noted that the first 3 years of life represent the most extensive period of brain growth and synapse development. “This early brain development shapes each child’s future potential and is critical to later educational and other outcomes,” Dr. Donald’s team notes.

MRI imaging is difficult under any circumstances in neonates and toddlers, a problem related to the difficulty of getting them to stay perfectly still for comparatively long periods of time. When medical issues are at stake, such children, in wealthy nations, are often placed under anesthesia before being placed in an MRI scanner for up to an hour. But this is considered to be unethical to do in the research setting, where illness is not present. Anesthesia carries a relatively small but real risk in all who receive it, perhaps more so in small children and especially those with respiratory issues.

The first purpose of Dr. Donald’s study, in view of this worldwide problem, was to test the feasibility of an approach to scanning very young children that does not rely upon anesthesia, or to methods used in older children such as subjecting them to a “simulated” scanning experience so as to acclimate them to the very odd sights and sounds that occur when one is placed inside a scanning vessel.

The method used by Dr. Donald’s team centers on performing MRI scanning while 2- and 3-year-olds are sleeping, and just as important, in creating an environment at the test center that enables parents to be with their children in a non-threatening setting in which the children eat a meal, engage in gentle play and then naturally fall asleep, with help from a small oral dose of melatonin, a hormonal sleep-promoting agent shown to be safe and effective in small children.

This method was attempted in a study population drawn from a larger study of young children in the area surrounding Cape Town, the Drakenstein Child Health study. After a small number of promising “pilot” scans, a group of 216 children underwent scanning during natural sleep. High-resolution images were obtained from 167 (77%). All participating children, part of a birth cohort, had received standard child developmental assessments at the age of 2 years.

Dr. Donald’s team came to two conclusions. One was that their approach to imaging very young children without use of anesthesia is fully feasible in a resource-challenged setting—successful in imaging a large majority of children, and consuming minimal medical and research resources. The team feels the method should also be considered for use in high-income parts of the world, even in clinical settings, since the new method exposes children to negligible side-effect risk.

The team also had scientific findings to share on the basis of close analysis of 146 sets of MRI and cognitive data on the children who were successfully scanned. They sought to determine whether regional variations in brain structure were associated with neurocognitive function at 2-3 years of age. They found that children’s neurocognitive development scores, measured at age 2 years, were associated with reduced thickness in cortical areas, and with increased surface area in certain brain regions. The thinning of the cortex is thought to be a reflection of the process called synaptic pruning, which eliminates unneeded connections, increasing the efficiency of parts of the cortex that give rise to complex thinking and which support language development.

The frontal areas identified by the team’s MRI scans receive and process inputs coming in from many other brain areas. This, says the team, supports the idea that structural maturation of such regions “is key to integrated higher-level function” that underlies healthy development of neural systems in the early years of life. The team’s next objective is to expand and follow the sample and to explore genetic and environmental influences on child development.