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

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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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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Respiratory, postural and spatio-kinetic motor stabilization, internal models, top-down timed motor coordination and expanded cerebello-cerebral circuitry: a review

Human dexterity, bipedality, and song/speech vocalization in Homo are reviewed within a motor evolution perspective in regard to 

(i) brain expansion in cerebello-cerebral circuitry, 
(ii) enhanced predictive internal modeling of body kinematics, body kinetics and action organization, 
(iii) motor mastery due to prolonged practice, 
(iv) task-determined top-down, and accurately timed feedforward motor adjustment of multiple-body/artifact elements, and 
(v) reduction in automatic preflex/spinal reflex mechanisms that would otherwise restrict such top-down processes. 

Dual-task interference and developmental neuroimaging research argues that such internal modeling based motor capabilities are concomitant with the evolution of 
(vi) enhanced attentional, executive function and other high-level cognitive processes, and that 
(vii) these provide dexterity, bipedality and vocalization with effector nonspecific neural resources. 

The possibility is also raised that such neural resources could 
(viii) underlie human internal model based nonmotor cognitions. 
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How gut sampling and microbial invasiveness/noninvasiveness provides mucosal immunity with a nonmolecular pattern means to distinguish commensals from pathogens: A review

Mucosal immunity distinguishes not only different microbial antigens but also separates those of pathogens from those of commensals. How this is done is unknown. The present view is that the pathogen/commensal determination of antigens depends upon as yet to be discovered molecular patterns. Here I review the biological feasibility that it also involves the detection of the invasive differences in their motility towards the gut wall when they are sampled by differently biased methods. 

By their nature, pathogens and commensals have different motility – invasive and noninvasive – in regard to the epithelium. The immune system is in a position to detect such motility differences. This biological opportunity arises since different microbe sampling methods can “catch” different groups of microbes depending upon how their motility interacts with the epithelium. A biological method biased to sample those with invasive motility—pathogens—could be achieved by ‘honey pot traps’ that preferentially (but not exclusively) sample microbes that have a taxis to breaches in the epithelium. A biological method biased to sample those that are noninvasive—commensals—could be done by capturing microbes that are passively and stably residing in the biofilm “offshore” of the epithelium. Such differential sampling strategies would seem to relate to those carried out respectively by (i) M-cells (working with subepithelial dome dendritic cells), and (ii) sub- and intraepithelial dendritic cells.

The interactions of antigen presentation can be arranged so that the immune system links antigens from biased microbial sampling with pathogenic or commensal appropriate immune responses. Such immune classification could feasibly occur biologically through a winner-take-all competition between inhibiting and activating antigen presentation. Winner-takes-all types of processing classification are already known to underlie the biologically interactions between neurons that classify sensory inputs making it also plausible that they are exploited by the immune system. In pathogen identification, M-cell antigens would be activating and biofilm antigens inhibitory, and vise versa for commensal identification. This winner-take-all competition between antigen presentation would act to amplify small statistical biases in the two samples linked to invasiveness/noninvasiveness into a reliable pathogen/commensal distinction. This process would both complement, and acts as independent guarantor, upon the alternative pathogenicity/commensality recognition provided by molecular pattern recognition. 

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Dyslexia and the assessment of visual attention

Visual stream segregation has been proposed as a method to measure visual attention in dyslexia. Another task proposed to do this is the line-motion illusion. Both tasks, it is observed, can be carried out with spatially distributed stimuli. This, however, appears inconsistent with these tasks being linked speci?cally to attentional processes since this would require them to spatially focus cognitive resources. Also, both line-motion and visual stream segregation involve the perception of movement raising the possibility that what is actually measured by these tasks is not attention but some aspect of motion perception

Extreme energy lability in human children: An overlooked and central aspect of human biology

A four year old child devotes half their total energy expenditure (TEE) to their brains. Even by 10 years-of-age it is still 30% (compared to an adult’s ≈12%). This extreme energy use results from a high brain/body size ratio – combined with a doubling of cerebral gray matter energy utilization (due to synaptic exuberance during cognitive neuromaturation). 

With extreme energy expenditure goes extreme vulnerability to hypoglycemia: (1) children become hypoglycemic after 24-36 hours of fast (compared to 60-72 hours in adults), and (2) their brains suffer neurological impairment (shown in disrupted P300 potentials) at a lower decrease in plasma glucose: 3.6 - 4.2 mmol L-1 in children rather than < 3.0 mmol L-1 in adults (against a normal level in both of 4.6-4.8 mmol L-1). Human biology has selected adaptations that buffer and protect children from this energy lability. A physiological one is that energy metabolism in skeletal muscles is biased towards using fatty acids, and this minimizes uptake competition of plasma glucose between muscles and the brain. Behavioral adaptations (in human hunter-gatherers) include adults cooperatively pooling high energy foods with juveniles for ≈15 years, this provides juveniles with a reliable ≈3.5-7 MJ per day. 

Hunter-gatherers share food with juveniles due to gossip enforced indirect reciprocity. This reciprocity depends for its existence upon adult cognitions that require prolonged energy- expensive neuromaturation. This raises the possibility that human adult cognitions are both a cause of children having extreme energy lability (by requiring prolonged energy expensive neuromaturation), and a means (by enabling indirect reciprocity) by which the risks of such lability are mitigated

Perceptual deficits and inattention in schizophrenia

A number of investigators have found perceptual deficits in schizophrenic subjects. It has also been indicated that those with schizophrenia suffer from reduced attention. This raises the possibility that their perceptual deficits may wholly or in part reflect attentional effects. The present study used computer simulations to examine the potential effects of inattention on performance measures determined with three psychophysical methods: the Two Alternative Forced Choice (2-AFC) Staircase Method, the Two Alternative Forced Choice (2-AFC) Fixed Stimuli Method, and the Yes/No Method. It is shown that both 2-AFC methods are susceptible to attentional effects but, in contrast, the Yes/No Method may allow for the differentiation of attentional effects from sensory sensitivity and subjective criterion effects. The simulations indicate that it may be possible to control for attention effects by using Yes/No Method in combination to a 2AFC method

A few remarks on the relationship between visuo-spatial attention deficits and dyslexia

Dyslexia and attentional problems are often comorbid. This raises the question whether reading deficits might etiologically follow from attentional difficulties, a hypothesis that has been proposed in regard to visuo-spatial attention deficits. This visuo-spatial attention deficit hypothesis would predict that attention deficits should be specific to dyslexia. However, it is here estimated that at the population level there are more non-dyslexic individuals than dyslexic individuals with visuo-spatial attention deficits. The reason for this is that in the overall population level there are far more individuals without dyslexia than with dyslexia. Thus, a relatively modest percentage presence of attention problems in the non-dyslexic population can result in a greater absolute number of on-dyslexic individuals with such problems. It is concluded that attention problems are unlikely to be specific to dyslexia