Cranial Connections: What they are and how they are affected in very preterm born infants
To run any complex piece of machinery, like your car for example, all the parts that make up the system need to work together. Your car won’t drive without wheels, the wheels won’t turn without engine fluid and gas, and you can’t start the engine without keys.
Likewise, the brain is a complex organ, made up of interconnected parts that communicate with each other to help us think, act, and feel. At a superficial glance, the brain is composed of white matter and gray matter structures. In order for our brains to function normally, common patterns of white matter and gray matter develop, from the time that we are in the womb, to the moment our brains reach maturity in early adulthood.
White matter is specifically important for forming pathways of communication from one area of the brain to another. You can think of these pathways as wires under the hood of your car that connect the battery to the engine, the engine to the brake booster, and so on. When there are injuries to white matter during development, there can be severe disruptions in these pathways. As a result, the way brain structures are connected (i.e., structural connectivity) and how they communicate to perform functions (i.e., functional connectivity) could change. In your car, this is similar to cutting the wires connecting to your brake booster; as a result, your brakes will require more force from your foot to bring your car to a stop. In human brains, these changes in structural and functional connectivity can manifest as disease states. For example, white matter injury in preterm born infants is associated with the development of cerebral palsy in later life (Cooper et al., 2017).
Infants born very preterm are at a high risk for white matter injury in early life. Very preterm birth is defined as birth at less than 32 weeks’ gestation. Although brain imaging instruments provide excellent tools for identifying the presence of white matter injury, as seen in Fig.1, in-depth quantitative analyses are needed to better understand the relationship between these white matter injuries and the resulting changes in structural and functional connectivity.
Dr. Emma Deurden, PhD, and colleagues (2019) recently conducted a study to address this issue. One goal of the study was to use a neuroimaging technique, called resting-state functional magnetic resonance imaging, to see whether functional connectivity is compromised in preterm born infants with white matter injury compared to preterm born babies without white matter injury. Another goal of the study was to use diffusion tensor imaging to see whether structural connectivity is compromised in infants with white matter injury compared to those without white mattery injury.
Functional magnetic resonance imaging is used to determine which regions of our brains function together. Oftentimes, researchers pair this type of imaging with a task; the resulting images provide a map of brain regions, that communicate with each other to help us perform the task in question (Crosson et al., 2010). However, some brain areas function together, even when we are sitting around doing nothing, and this is termed resting state functional connectivity. Diffusion tensor imaging is a different form of neuroimaging that allows researchers to describe the location, direction, and strength of connections between brain regions (Crosson et al., 2010).
Fig 1. Images of white matter injury (red arrows) in two infant brains. White matter injuries are seen as “hyperintensities” or whiter regions. Duerden et al. (2019)
After using resting state functional imaging and diffusion tensor imaging in their study, Duerden and colleagues (2019) described novel findings about white matter injury in very preterm born infants. Namely, the authors found that white matter changes were located in white matter connecting the two hemispheres of the brain (i.e., the corpus callosum), white matter connecting the brainstem to cortical regions (the outer regions of the brain), as well as projections connecting the thalamus to cortical regions of the brain (i.e., thalamic radiations).
The thalamus is often called the “relay station” of the brain, as it is responsible for taking in sensory information and passing it along to areas of the brain for complex processing, such as the cortical areas. In preterm born infants with white matter injury, injury size was greatest in the posterior thalamic radiation. Collectively, these results demonstrate that there is a distinct pattern of white matter injury in very preterm born infants that affects how brain regions connect and function together.
Fig 2. Thalamic radiations, corpus callosum, and corona radiata (unshown projections from the brain stem to the cortex) are prone to white matter injury in very preterm born infants. Created using BioRender.com
With their quantitative neuroimaging techniques, the implication of the work done by Dr. Duerden and colleagues at Western’s Developing Brain Lab is two-fold: 1) mapping out areas of greatest vulnerability to white matter injury in very preterm infants will help researchers better understand associated disease states, and 2) identifying white matter areas more prone to injury paves the way for future research on biomarkers (i.e., identifiable biological signs) for infants and pregnancies at high risk for white matter injury.
Original Article: Duerden, E.G., Halani, S., Ng, K., Guo, T., Foong, J., Glass, J.A.T., Chau, V., Branson, H.M., Sled, J.G., Whyte, H.E., Kelly, E.D., and Miller, S.P. (2019). White matter injury predicts disrupted functional connectivity and microstructure in very preterm born neonates. NeuroImage: Clinical, 21(101596), 1–7.
References
Cooper, M.S., Mackay, M.T., Fahey, M., Reddihough, D., Reid, S.M., Williams, K., and Harvey, A.S. (2017). Seizures in children with cerebral palsy and white matter injury. Pediatrics, 139(3), 1–11.