Human neuromaturation, juvenile extreme energy liability, and adult cognition/cooperation

Human childhood and adolescence is the period in which adult cognitive competences (including those that create the unique cooperativeness of humans) are acquired. It is also a period when neural development puts a juvenile’s survival at risk due to the high vulnerability of their brain to energy shortage. The brain of a 4 year-old human uses ≈50% of its total energy expenditure (TEE) (cf. adult ≈12%). This brain expensiveness is due to (1) the brain making up ≈6% of a 4 year-old body compared to 2% in an adult, and (2) increased energy metabolism that is ≈100% greater in the gray matter of a child than in an adult (a result of the extra costs of synaptic neuromaturation). The high absolute number of neurons in the human brain requires as part of learning a prolonged neurodevelopment. This refines inter- and intraarea neural networks so they become structured with economical “small world” connectivity attributes (such as hub organization and high cross-brain differentiation/integration). Once acquired, this connectivity enables highly complex adult cognitive capacities. Humans evolved as hunter-gatherers. Contemporary hunter-gatherers (and it is also likely Middle Paleolithic ones) pool high energy foods in an egalitarian manner that reliably supported mothers and juveniles with high energy intake. This type of sharing unique to humans protects against energy shortage happening to the immature brain. This cooperation that protects neuromaturation arises from adults having the capacity to communicate and evaluate social reputation, cognitive skills that exist as a result of extended neuromaturation. Human biology is therefore characterized by a presently overlooked bioenergetic-cognition loop (called here the “HEBE ring”) by which extended neuromaturation creates the cooperative abilities in adults that support juveniles through the potentially vulnerable period of the neurodevelopment needed to become such adults

Dynamic myelin regulation as a novel form of neural plasticity

Dynamic changes in myelin could optimize information transmission in neuralcircuits and enhance conduction velocity. This review aimed to provide anunderstanding of how dynamic myelin plasticity is important in neuronalactivity and how astrocytes have an important role that is not equal in theperipheral nervous system. Myelin is dynamically regulated by neuronalactivity. It takes part continuously in nervous system plasticity duringdevelopment. Newly differentiating oligodendrocytes can create a new myelinsheath. Mature myelin sheaths can grow again in adults. Oligodendrocytesinteract with astrocytes in the central nervous system through gap junctions.Astrocytes have an important role as synaptic network integrators; therefore,decreasing astrocyte numbers will cause a loss of presynaptic plasticity. Theconcept considers plasticity as a mechanism that depends on myelination.Higher brain functions and myelination interplay in the hippocampus andprefrontal cortex. The mechanism and function of these changes remainpoorly understood. Genetic, neural activity, environment, and axonal activitymight play important roles. Dynamic myelin regulation reveals a new form ofneural plasticity. Myelination is similar to synapse formation and plasticity. Itenables plasticity in the central nervous system and helps improve the learningprocess

MR connectomics: a conceptual framework for studying the developing brain

The combination of advanced neuroimaging techniques and major developments in complex network science, have given birth to a new framework for studying the brain: “connectomics.” This framework provides the ability to describe and study the brain as a dynamic network and to explore how the coordination and integration of information processing may occur. In recent years this framework has been used to investigate the developing brain and has shed light on many dynamic changes occurring from infancy through adulthood. The aim of this article is to review this work and to discuss what we have learned from it. We will also use this body of work to highlight key technical aspects that are necessary in general for successful connectome analysis using today's advanced neuroimaging techniques. We look to identify current limitations of such approaches, what can be improved, and how these points generalize to other topics in connectome research

Splenium of corpus callosum: patterns of interhemispheric interaction in children and adults.

The splenium of the corpus callosum connects the posterior cortices with fibers varying in size from thin late-myelinating axons in the anterior part, predominantly connecting parietal and temporal areas, to thick early-myelinating fibers in the posterior part, linking primary and secondary visual areas. In the adult human brain, the function of the splenium in a given area is defined by the specialization of the area and implemented via excitation and/or suppression of the contralateral homotopic and heterotopic areas at the same or different level of visual hierarchy. These mechanisms are facilitated by interhemispheric synchronization of oscillatory activity, also supported by the splenium. In postnatal ontogenesis, structural MRI reveals a protracted formation of the splenium during the first two decades of human life. In doing so, the slow myelination of the splenium correlates with the formation of interhemispheric excitatory influences in the extrastriate areas and the EEG synchronization, while the gradual increase of inhibitory effects in the striate cortex is linked to the local inhibitory circuitry. Reshaping interactions between interhemispherically distributed networks under various perceptual contexts allows sparsification of responses to superfluous information from the visual environment, leading to a reduction of metabolic and structural redundancy in a child's brain

Human metabolic adaptations and prolonged expensive neurodevelopment: A review

1.	After weaning, human hunter-gatherer juveniles receive substantial (≈3.5-7 MJ day^-1^), extended (≈15 years) and reliable (kin and nonkin food pooling) energy provision.
2.	The childhood (pediatric) and the adult human brain takes a very high share of both basal metabolic rate (BMR) (child: 50-70%; adult: ≈20%) and total energy expenditure (TEE) (child: 30-50%; adult: ≈10%).
3.	The pediatric brain for an extended period (≈4-9 years-of-age) consumes roughly 50% more energy than the adult one, and after this, continues during adolescence, at a high but declining rate. Within the brain, childhood cerebral gray matter has an even higher 1.9 to 2.2-fold increased energy consumption. 
4.	This metabolic expensiveness is due to (i) the high cost of synapse activation (74% of brain energy expenditure in humans), combined with (ii), a prolonged period of exuberance in synapse numbers (up to double the number present in adults). Cognitive development during this period associates with volumetric changes in gray matter (expansion and contraction due to metabolic related size alterations in glial cells and capillary vascularization), and in white matter (expansion due to myelination). 
5.	Amongst mammals, anatomically modern humans show an unique pattern in which very slow musculoskeletal body growth is followed by a marked adolescent size/stature spurt. This pattern of growth contrasts with nonhuman primates that have a sustained fast juvenile growth with only a minor period of puberty acceleration. The existence of slow childhood growth in humans has been shown to date back to 160,000 BP. 
6.	Human children physiologically have a limited capacity to protect the brain from plasma glucose fluctuations and other metabolic disruptions. These can arise in adults, during prolonged strenuous exercise when skeletal muscle depletes plasma glucose, and produces other metabolic disruptions upon the brain (hypoxia, hyperthermia, dehydration and hyperammonemia). These are proportional to muscle mass.
7.	Children show specific adaptations to minimize such metabolic disturbances. (i) Due to slow body growth and resulting small body size, they have limited skeletal muscle mass. (ii) They show other adaptations such as an exercise specific preference for free fatty acid metabolism. (iii) While children are generally more active than adolescents and adults, they avoid physically prolonged intense exertion. 
8.	Childhood has a close relationship to high levels of energy provision and metabolic adaptations that support prolonged synaptic neurodevelopment. 
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The infancy of the human brain

The human infant brain is the only known machine able to master a natural language and develop explicit, symbolic, and communicable systems of knowledge that deliver rich representations of the external world. With the emergence of non-invasive brain imaging, we now have access to the unique neural machinery underlying these early accomplishments. After describing early cognitive capacities in the domains of language and number, we review recent findings that underline the strong continuity between human infants’ and adults’ neural architecture, with notably early hemispheric asymmetries and involvement of frontal areas. Studies of the strengths and limitations of early learning, and of brain dynamics in relation to regional maturational stages, promise to yield a better understanding of the sources of human cognitive achievements.This work was supported by the Center for Brains, Minds and Machines (CBMM), funded by NSF STC award CCF – 1231216

Oligodendroglial GABAergic Signaling: More Than Inhibition!

GABA is the main inhibitory neurotransmitter in the CNS acting at two distinct types of receptor: ligand-gated ionotropic GABAA receptors and G protein-coupled metabotropic GABAB receptors, thus mediating fast and slow inhibition of excitability at central synapses. GABAergic signal transmission has been intensively studied in neurons in contrast to oligodendrocytes and their precursors (OPCs), although the latter express both types of GABA receptor. Recent studies focusing on interneuron myelination and interneuron-OPC synapses have shed light on the importance of GABA signaling in the oligodendrocyte lineage. In this review, we start with a short summary on GABA itself and neuronal GABAergic signaling. Then, we elaborate on the physiological role of GABA receptors within the oligodendrocyte lineage and conclude with a description of these receptors as putative targets in treatments of CNS diseases

Myelin: A gatekeeper of activity-dependent circuit plasticity?

The brain is responsive to an ever-changing environment, enabling the organism to learn and change behaviour accordingly. Efforts to understand the underpinnings of this plasticity have almost exclusively focussed on the functional and underlying structural changes that neurons undergo at neurochemical synapses. What has received comparatively little attention is the involvement of activity-dependent myelination in such plasticity and the functional output of circuits controlling behaviour. The traditionally held view of myelin as a passive insulator of axons is changing to one of lifelong changes in myelin, modulated by neuronal activity and experience. Here we review the nascent evidence of the functional role of myelin plasticity in strengthening circuit functions that underlie learning and behaviourEuropean Research Council Paul G. Allen Frontiers Group UK Multiple Sclerosis Society Lister Institute of Preventive Medicine Medical Research Counci