What Is the Metabolic Mechanism of Brain Functional Development During Infancy?

By Kate Knab

The Findings

Infant cerebral blood flow (CBF) delivers nutrients and oxygen to infants’ brains to support the fastest period of postnatal brain development. With unprecedented spatiotemporal precision of infant CBF maps, a collaborative team of researchers discovered the emergence of a physiological cortical hierarchy — the understanding of how the cortex is principally organized and how the cortical gradient emerges — that guides this process. 

The researchers noted that as an infant grows, CBF increases along the limbic-sensorimotor-association cortical gradient, which is a spatial pattern in the brain that allows basic sensory and motor functions to transition gradually to areas associated with more complex cognitive processing related to motivations and emotions.

The study team found that these changes in CBF were associated with improved developmental functioning, suggesting that this cortical hierarchy likely underlies the enhanced development of different regions of the brain dedicated to specific functions.

Why It Matters

CBF supplies the energy required to support the intense developmental processes that occur most dramatically between infancy and two years of life. While the brain doubles in size during this time, it is also vulnerable to brain disorders and injuries that may occur if blood flow is interrupted or inadequate. Similarly, behavioral development is also impacted by CBF.

This study fills a knowledge gap regarding organizing principles of CBF dynamics that contribute to the emergence of a specialized cortical gradient. Scientists now better understand the metabolic mechanism of how brain regions use energy to support functional specialization during the critical time of infant growth and development.

The outcome of this study also offers a standardized clinical reference for infant CBF for potential early detection of biomarkers for disorders such as autism.

Who Conducted the Study

Scientists from the Department of Radiology at Children’s Hospital of Philadelphia conducted this study, including first author and Assistant Professor of Radiology, Minhui Ouyang, PhD from the Huang Laboratory for Intelligent Neuroimaging and Brain Connectivity (LINBC); and  co-authors Clinical Psychologist Emily Kuschner, PhD, and Associate Professor of Radiology J. Christopher Edgar, PhD. Corresponding and senior author Hao Huang, PhD, Professor in Radiology at CHOP and Director of the LINBC Lab, designed and performed the study by collaboration with colleagues from the University of Pennsylvania and Beijing Children’s Hospital.

How They Did It

Researchers obtained the highest resolution CBF maps available to date to capture the 4D spatiotemporal CBF changes with unprecedented precision in 134 infant brains characterized by small sizes. The LINBC Lab and John Detre’s Lab at Penn developed a cutting-edge infant version of pseudo-continuous resolution arterial spin labeled (ASL) magnetic resonance imaging (MRI) technique with 3D multi-shot stack-of-spirals readout and background suppression. ASL can noninvasively and magnetically label arterial blood water protons for estimating CBF maps. 

Data-driven clustering analysis also revealed three clusters along the hierarchical limbic-sensorimotor-association gradient with unique CBF increase patterns in the limbic, sensorimotor, and frontoparietal regions.

Quick Thoughts

“This infant brain physiological hierarchy reveals insights into the metabolic mechanism of early brain development and behavioral manifestation,” Dr. Ouyang said. “These highest-resolution infant cerebral blood flow maps offer normal reference for basic neuroscience and early detection of clinical biomarkers in disorders such as autism, neonatal stroke, hypoxic-ischemic encephalopathy and congenital heart disease.”

What’s Next

Future studies combining CBF with neuroimaging measures from other modalities could reveal multidimensional principles of infant brain maturation. With rapid MRI technical advances in hardware and sequence, the study team is investigating clinical applications for the imaging technique they developed to obtain high-resolution infant CBF.

Where the Study Was Published

The study appears in Nature Communications.