Closed-loop digital meditation for neurocognitive and behavioral development in adolescents with childhood neglect.

Adverse childhood experiences are linked to poor attentive behaviors during adolescence, as well as increased risk for mental health disorders in adults. However, no study has yet tested targeted interventions to optimize neurocognitive processes in this population. Here, we investigated closed-loop digital interventions in a double-blind randomized controlled study in adolescents with childhood neglect, and evaluated the outcomes using multimodal assessments of neuroimaging, cognitive, behavioral, and academic evaluations. In the primary neuroimaging results, we demonstrate that a closed-loop digital meditation intervention can strengthen functional connectivity of the dorsal anterior cingulate cortex (dACC) in the cingulo-opercular network, which is critically developing during the adolescent period. Second, this intervention enhanced sustained attention and interference-resolution abilities, and also reduced behavioral hyperactivity at a 1-year follow-up. Superior academic performance was additionally observed in adolescents who underwent the digital meditation intervention. Finally, changes in dACC functional connectivity significantly correlated with improvements in sustained attention, hyperactivity, and academic performance. This first study demonstrates that closed-loop digital meditation practice can facilitate development of important aspects of neurocognition and real-life behaviors in adolescents with early childhood neglect

Optic radiation structure and anatomy in the normally developing brain determined using diffusion MRI and tractography

The optic radiation (OR) is a component of the visual system known to be myelin mature very early in life. Diffusion tensor imaging (DTI) and its unique ability to reconstruct the OR in vivo were used to study structural maturation through analysis of DTI metrics in a cohort of 90 children aged 5–18 years. As the OR is at risk of damage during epilepsy surgery, we measured its position relative to characteristic anatomical landmarks. Anatomical distances, DTI metrics and volume of the OR were investigated for age, gender and hemisphere effects. We observed changes in DTI metrics with age comparable to known trajectories in other white matter tracts. Left lateralization of DTI metrics was observed that showed a gender effect in lateralization. Sexual dimorphism of DTI metrics in the right hemisphere was also found. With respect to OR dimensions, volume was shown to be right lateralised and sexual dimorphism demonstrated for the extent of the left OR. The anatomical results presented for the OR have potentially important applications for neurosurgical planning

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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Uncovering the Social Deficits in the Autistic Brain. A Source-Based Morphometric Study

Autism is a neurodevelopmental disorder that mainly affects social interaction and communication. Evidence from behavioral and functional MRI studies supports the hypothesis that dysfunctional mechanisms involving social brain structures play a major role in autistic symptomatology. However, the investigation of anatomical abnormalities in the brain of people with autism has led to inconsistent results. We investigated whether specific brain regions, known to display functional abnormalities in autism, may exhibit mutual and peculiar patterns of covariance in their gray-matter concentrations. We analyzed structural MRI images of 32 young men affected by autistic disorder (AD) and 50 healthy controls. Controls were matched for sex, age, handedness. IQ scores were also monitored to avoid confounding. A multivariate Source-Based Morphometry (SBM) was applied for the first time on AD and controls to detect maximally independent networks of gray matter. Group comparison revealed a gray-matter source that showed differences in AD compared to controls. This network includes broad temporal regions involved in social cognition and high-level visual processing, but also motor and executive areas of the frontal lobe. Notably, we found that gray matter differences, as reflected by SBM, significantly correlated with social and behavioral deficits displayed by AD individuals and encoded via the Autism Diagnostic Observation Schedule scores. These findings provide support for current hypotheses about the neural basis of atypical social and mental states information processing in autism

Gyrification, cortical and subcortical morphometry in neurofibromatosis type 1: an uneven profile of developmental abnormalities.

Background: Neurofibromatosis type 1 (NF1) is a monogenic disorder associated with cognitive impairments. In order to understand how mutations in the NF1 gene impact brain structure it is essential to characterize in detail the brain structural abnormalities in patients with NF1. Previous studies have reported contradictory findings and have focused only on volumetric measurements. Here, we investigated the volumes of subcortical structures and the composite dimensions of the cortex through analysis of cortical volume, cortical thickness, cortical surface area and gyrification. Methods: We studied 14 children with NF1 and 14 typically developing children matched for age, gender, IQ and right/left-handedness. Regional subcortical volumes and cortical gyral measurements were obtained using the FreeSurfer software. Between-group differences were evaluated while controlling for the increase in total intracranial volume observed in NF1. Results: Subcortical analysis revealed disproportionately larger thalami, right caudate and middle corpus callosum in patients with NF1. Cortical analyses on volume, thickness and surface area were however not indicative of significant alterations in patients. Interestingly, patients with NF1 had significantly lower gyrification indices than typically developing children primarily in the frontal and temporal lobes, but also affecting the insula, cingulate cortex, parietal and occipital regions. Conclusions: The neuroanatomic abnormalities observed were localized to specific brain regions, indicating that particular areas might constitute selective targets for NF1 gene mutations. Furthermore, the lower gyrification indices were accompanied by a disproportionate increase in brain size without the corresponding increase in folding in patients with NF1. Taken together these findings suggest that specific neurodevelopmental processes, such as gyrification, are more vulnerable to NF1 dysfunction than others. The identified changes in brain organization are consistent with the patterns of cognitive dysfunction in the NF1 phenotype. © 2013 Violante et al

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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