The human brain is distinguished by costly energetic demands and enhanced plasticity. This combination of factors underlies some of the most unique cognitive capacities of our species. The brain's capacity for learning is greatest during childhood and involves the formation and refinement of new neuronal connections. This process is driven by high rates of energy consumption. This research project will identify the genetic changes during evolution that brought about the human brain and explore the causal link between the development of brain plasticity and metabolism.
A major aim of this project involves charting the changes in the brain's energy utilization during the different maturational stages of humans. To accomplish this goal, the interdisciplinary team is using positron emission tomography scans of brain glucose consumption over the course of development from birth to adult stages. These results will be integrated with the patterns presented by RNA and protein data on the thousands of genes that are expressed at changing levels in different brain regions across the same developmental stages. Comparative data on the developmental expression of proteins and neuron morphology in great apes and macaque monkeys are also being obtained to determine whether the progression of molecular and cellular changes in human brain development are distinctively different from our close relatives. The investigators expect to find coordinated expression patterns in brain energetic and brain plasticity genes showing evidence that adaptive evolution occurred in their regulatory machinery during the origin of humans. The results should provide important clues about the organization and function of the molecular machinery that underpins the type of human brain plasticity that gives our species its exceptional capacity to incorporate experience and learning into the production of culture.
By focusing attention on brain energetic and brain plasticity genes that show adaptive evolution during recent human ancestry but are currently fixed across human populations, this project's focus on shared genes that define human cognitive abilities reinforces the conclusion of a common humanity. Thus the results of this project should be of interest to the general public and to scientists across a wide variety of disciplines, including anthropology, neuroscience, molecular evolution, bioenergetics, endocrinology and pediatrics. Experimental determination of total brain energetics during growth will enhance our ability to understand the age-specific tradeoffs that the acquisition of larger brains would have required during human evolutionary history, while also providing a new context in which to understand metabolic diseases such as diabetes. Furthermore, this project will advance research and education by providing training opportunities for individuals at the undergraduate, graduate and postdoctoral levels.
A multidisciplinary team of scientists has investigated how the evolutionarily distinctive human life history strategy of slow development and increased longevity impact the cerebral cortex over the lifespan. We have shown that the process of myelination, which involves the addition of a fatty insulating sheath surrounding axons to improve the efficiency of their signaling, is prolonged in humans relative to other primates. Human neonates are born with absolutely fewer myelinated axons in the neocortex and take a longer period through development to achieve fully mature, adult-like levels of myelination. Only in humans, but not in chimpanzees or macaque monkeys, does myelination continue to progress beyond the time of puberty. This unique pattern of slow development of cortical connectivity might be important for our species’ enhanced capacity to incorporate social learning in the elaboration of culture and technical skill learning. In contrast to the human-specific prolongation of myelination, our research has also shown that synapse formation in the chimpanzee neocortex follows a similar developmental schedule as in humans. In both humans and chimpanzees, the peak of synapse over-production, which occurs prior to subsequent activity-dependent pruning, takes place in the mid-juvenile period. In macaque monkeys, which are more distantly related to humans, it had previously been shown that the peak of synaptogenesis occurs in infancy within the first few postnatal months. Therefore, our findings indicate that an increased capacity for learning throughout juvenile life may be supported by a developmental pattern of extended synapse refinement that is a shared trait among humans and chimpanzees. The developing human brain requires a tremendous amount of energy due to the costs of synapse over-production in the cerebral cortex. However, prior estimates of the proportion of the total body’s energy budget that is devoted to the brain were based on imprecise extrapolations from adult data. We combined positron-emission tomography and magnetic resonance imaging data to more accurately calculate the human brain’s glucose use from birth to adulthood, which we compared to body growth rate. Our results showed that the brain’s energetic demand does not peak at birth, but rather in mid-childhood (65% of resting metabolic rate of the total body). Body weight growth and brain energy uptake are strongly, inversely related: soon after birth, increases in brain glucose demand are accompanied by proportionate decreases body growth rate. The finding that human brain glucose demands peak during childhood, and evidence that brain metabolism and body growth rate covary inversely across development, supports the hypothesis that the high costs of human brain development require compensatory slowing of body growth rate. These results might help to explain the phase of slow body growth in childhood that uniquely characterizes development in humans.
