Adult-like Levels Research Articles

Amino acid signatures in the developing mouse retina

This study characterizes the developmental patterns of seven key amino acids: glutamate, γ-amino-butyric acid (GABA), glycine, glutamine, aspartate, alanine and taurine in the mouse retina. We analyze amino acids in specific bipolar, amacrine and ganglion cell sub-populations (i.e. GABAergic vs. glycinergic amacrine cells) and anatomically distinct regions of photoreceptors and Müller cells (i.e. cell bodies vs. endfeet) by extracting data from previously described pattern recognition analysis. Pattern recognition statistically classifies all cells in the retina based on their neurochemical profile and surpasses the previous limitations of anatomical and morphological identification of cells in the immature retina. We found that the GABA and glycine cellular content reached adult-like levels in most neurons before glutamate. The metabolic amino acids glutamine, aspartate and alanine also reached maturity in most retinal cells before eye opening. When the overall amino acid profiles were considered for each cell group, ganglion cells and GABAergic amacrine cells matured first, followed by glycinergic amacrine cells and finally bipolar cells. Photoreceptor cell bodies reached adult-like amino acid profiles at P7 whilst Müller cells acquired typical amino acid profiles in their cell bodies at P7 and in their endfeet by P14. We further compared the amino acid profiles of the C57Bl/6J mouse with the transgenic X-inactivation mouse carrying the lacZ gene on the X chromosome and validated this animal model for the study of normal retinal development. This study provides valuable insight into normal retinal neurochemical maturation and metabolism and benchmark amino acid values for comparison with retinal disease, particularly those which occur during development.

Fast development of global motion processing in human infants

Although global motion processing is thought to emerge early in infancy, there is debate regarding the age at which it matures to an adult-like level. In the current study, we address the possibility that the apparent age-related improvement in global motion processing might be secondary to age-related increases in the sensitivity of mechanisms (i.e., local motion detectors) that provide input to global motion mechanisms. To address this, we measured global motion processing by obtaining motion coherence thresholds using stimuli that were equally detectable in terms of contrast across all individuals and ages (3-, 4-, 5-, 6-, and 7-month-olds and adults). For infants, we employed a directional eye movement (DEM) technique. For adults, we employed both DEM and a self-report method. First, contrast sensitivity was obtained for a local task, using a stochastic motion display in which all the dots moved coherently. Contrast sensitivity increased significantly between 3 and 7 months, and between infancy and adulthood. Each subject was then tested on the global motion task with the contrast of the dots set to 2.5 × each individual's contrast threshold. Coherence thresholds were obtained by varying the percentage of coherently moving "signal" versus "noise" dots in the stochastic motion display. Results revealed remarkably stable global motion sensitivity between 3 and 7 months of age, as well as between infancy and adulthood. These results suggest that the mechanisms underlying global motion processing develop to an adult-like state very quickly.

Perception of spectrally degraded reflexives and pronouns by children

Speech perception skills in cochlear-implant users are often measured with simple speech materials. In children, it is crucial to fully characterize linguistic development, and this requires linguistically more meaningful materials. The authors propose using the comprehension of reflexives and pronouns, as these specific skills are acquired at different ages. According to the literature, normal-hearing children show adult-like comprehension of reflexives at age 5, while their comprehension of pronouns only reaches adult-like levels around age 10. To provide normative data, a group of younger children (5 to 8 yrs old), older children (10 and 11 yrs old), and adults were tested under conditions without or with spectral degradation, which simulated cochlear-implant speech transmission with four and eight channels. The results without degradation confirmed the different ages of acquisition of reflexives and pronouns. Adding spectral degradation reduced overall performance; however, it did not change the general pattern observed with non-degraded speech. This finding confirms that these linguistic milestones can also be measured with cochlear-implanted children, despite the reduced quality of sound transmission. Thus, the results of the study have implications for clinical practice, as they could contribute to setting realistic expectations and therapeutic goals for children who receive a cochlear implant.

Morphological constraints in children’s spoken language comprehension: A visual world study of plurals inside compounds in English

Many previous studies have shown that the human language processor is capable of rapidly integrating information from different sources during reading or listening. Yet, little is known about how this ability develops from child to adulthood. To gain insight into how children (in comparison to adults) handle different kinds of linguistic information during on-line language comprehension, the current study investigates a well-known morphological phenomenon that is subject to both structural and semantic constraints, the plurals-in-compounds effect, i.e. the dislike of plural (specifically regular plural) modifiers inside compounds (e.g. rats eater). We examined 96 seven-to-twelve-year-old children and a control group of 32 adults measuring their eye-gaze changes in response to compound-internal plural and singular forms. Our results indicate that children rely more upon structural properties of language (in the present case, morphological cues) early in development and that the ability to efficiently integrate information from multiple sources takes time for children to reach adult-like levels.

Should minors be considered as potential living liver donors?

For many patients, living donor liver transplantation represents their only hope of receiving a lifesaving graft. In certain (albeit rare) cases, a minor will be the only suitable donor. Living liver donation by minors has been reported in several countries. In the academic literature and professional guidelines, little attention is paid to the development of an ethical framework for this practice. The focus is frequently limited to the donation of regenerative tissues and kidneys. However, liver donation differs in important respects because of the increased medical risks and the lack of substitute therapies. Therefore, in this article, we assess whether living liver donation by minors is ethically appropriate. We argue that living liver donation by minors is justifiable only if minors possess the capacity to consent to donation or if the procedure is in their best interests. Although minors may possess adult-like levels of cognitive maturity, they lack sufficient psychosocial maturity to give valid consent to donation. In addition, living liver donation is generally not in a minor's best interests. With respect to the latter, the potential psychological benefits that a minor may experience as a result of living liver donation are insufficiently empirically supported and are unlikely to outweigh the short- and long-term medical and psychological risks. Therefore, we conclude that minors should not be considered as potential living liver donors.

Developmental Changes in Postural Stability During the Performance of a Precision Manual Task

Posture becomes integrated with other goal-directed behaviors early in infancy and continues to develop into the second decade of life. However, the developmental time course over which posture is stabilized relative to the base of support during a dynamic manual precision task has not been examined. Postural-manual integration was assessed in 7-year-olds, 10-year-olds, and adults using a postural-manual task in which task precision (target fitting size) and postural difficulty (reaching distance to a target) were manipulated. The main dependent variable was postural time-to-contact (TtC). Results indicated systematic age effects in which TtC was shortest in the 7-year-olds, increased in the 10-year-olds, and was longest in the adults. Across all age levels, TtC was longer when performing a precision ft compared with a nonprecision ft and when fitting at a near target compared with fitting at a far target. Finally, TtC increased over the course of the manual fitting task, suggesting that posture became increasingly stable as the hand approached the opening. The ability to modulate postural TtC during the course of the fitting trial was most pronounced in adults as compared with both groups of children. These results suggest that even by 10-years of age, children are not yet able to fully integrate postural movements with goal directed manual tasks at adult-like levels.

The implicit use of spatial information develops later for crossmodal than for intramodal temporal processing

The integrated use of spatial and temporal information seems to support the separation of two sensory streams. The present study tested whether this facilitation depends on the encoding of sensory stimuli in externally anchored spatial coordinate systems. Fifty-nine children between 5 and 12years as well as 12 young adults performed a crossmodal temporal order judgment (TOJ) task for simple visual and tactile stimuli. Stimuli were presented either within the same or in different hemifields. Presentation of the two modality inputs in different hemifields improved TOJ only in children aged 10years and older. In contrast, intramodal TOJ performance (data from Pagel, Heed, & Röder, 2009) was better than crossmodal TOJ performance starting at the age of 6years. An adult-like level of performance in the crossmodal TOJ task was evident only at the age of 12years. We speculate that the ability to redundantly code sensory input in modality-specific and modality-independent spatial coordinates facilitates intramodal temporal processing. Further refinement of the processes providing external spatial coordinates then results in the integrated use of space and time to decide whether sensory inputs belong to a common object or to separate events.

Prolonged myelination in human neocortical evolution

Nerve myelination facilitates saltatory action potential conduction and exhibits spatiotemporal variation during development associated with the acquisition of behavioral and cognitive maturity. Although human cognitive development is unique, it is not known whether the ontogenetic progression of myelination in the human neocortex is evolutionarily exceptional. In this study, we quantified myelinated axon fiber length density and the expression of myelin-related proteins throughout postnatal life in the somatosensory (areas 3b/3a/1/2), motor (area 4), frontopolar (prefrontal area 10), and visual (areas 17/18) neocortex of chimpanzees (N = 20) and humans (N = 33). Our examination revealed that neocortical myelination is developmentally protracted in humans compared with chimpanzees. In chimpanzees, the density of myelinated axons increased steadily until adult-like levels were achieved at approximately the time of sexual maturity. In contrast, humans displayed slower myelination during childhood, characterized by a delayed period of maturation that extended beyond late adolescence. This comparative research contributes evidence crucial to understanding the evolution of human cognition and behavior, which arises from the unfolding of nervous system development within the context of an enriched cultural environment. Perturbations of normal developmental processes and the decreased expression of myelin-related molecules have been related to psychiatric disorders such as schizophrenia. Thus, these species differences suggest that the human-specific shift in the timing of cortical maturation during adolescence may have implications for vulnerability to certain psychiatric disorders.

The development of speed discrimination abilities

The processing of speed is a critical part of a child’s visual development, allowing children to track and interact with moving objects. Despite such importance, no study has investigated the developmental trajectory of speed discrimination abilities or precisely when these abilities become adult-like. Here, we measured speed discrimination thresholds in 5-, 7-, 9-, 11-year-olds and adults using random dot stimuli with two different reference speeds (slow: 1.5deg/s; fast: 6deg/s). Sensitivity for both reference speeds improved exponentially with age and, at all ages, participants were more sensitive to the faster reference speed. However, sensitivity to slow speeds followed a more protracted developmental trajectory than that for faster speeds. Furthermore, sensitivity to the faster reference speed reached adult-like levels by 11years, whereas sensitivity to the slower reference speed was not yet adult-like by this age. Different developmental trajectories may reflect distinct systems for processing fast and slow speeds. The reasonably late development of speed processing abilities may be due to inherent limits in the integration of neuronal responses in motion-sensitive areas in early childhood.

The acquisition of the active transitive construction in English: A detailed case study

Abstract In this study, we test a number of predictions concerning children's knowledge of the transitive Subject-Verb-Object (SVO) construction between two and three years on one child (Thomas) for whom we have densely collected data. The data show that the earliest SVO utterances reflect earlier use of those same verbs, and that verbs acquired before 2;7 show an earlier move towards adult-like levels of use in the SVO construction and in object argument complexity than later acquired verbs. There is not a close relation with the input in the types of subject and object referents used, nor a close adherence to Preferred Argument Structure (PAS) before 2;7, but both early and late acquired verbs show a simultaneous move towards PAS patterns in selection of referent type at 2;9. The event semantics underpinning early transitive utterances do not straightforwardly fit prototype (high or inalienable) notions of transitivity, but rather may reflect sensitivity to animacy and intentionality in a way that mirrors the input. We conclude that children's knowledge of the transitive construction continues to undergo significant development between 2;0 and 3;0, reflecting the gradual abstraction and integration of the SVO and VO constructions, verb semantics, discourse pragmatics, and the interactions between these factors. These factors are considered in the context of a prototype for the transitive construction.

The development of visual working memory capacity during early childhood

The change detection task has been used in dozens of studies with adults to measure visual working memory capacity. Two studies have recently tested children in this task, suggesting a gradual increase in capacity from 5years to adulthood. These results contrast with findings from an infant looking paradigm suggesting that capacity reaches adult-like levels within the first year. The current study adapted the change detection task for use with children younger than 5years to test whether the standard version of the task was too difficult and may have underestimated children’s capacity. Results showed that 3- and 4-year-olds could successfully complete this modified task and that capacity increased roughly linearly, from 2 or 3 items during this period to 3 or 4 items between 5 and 7years. Furthermore, performance did not differ significantly between the modified version and a replication of the standard version with 5- and 7-year-olds. Thus, there is no evidence that previous research with the change detection task underestimated children’s capacity. Further research is needed to understand how performance relates across the infant looking task and change detection to provide a more complete picture of visual working memory capacity over development.

Gradual improvement in fine-grained sensitivity to triadic gaze after 6 years of age

The current research compared the ability of adults and children to determine where another person is looking in shared visual space (triadic gaze). In Experiment 1, children (6-, 8-, 10-, and 14-year-olds) and adults viewed photographs of a model fixating a series of positions separated by 1.6° along the horizontal plane. The task was to indicate whether the model was looking to the left or right of one of three target positions (midline, 6.4° left, or 6.4° right). By 6 years of age, thresholds were quite small ( M = 1.94°) but were roughly twice as large as those of adults ( M = 1.05°). Thresholds decreased to adult-like levels around 10 years of age. All age groups showed the same pattern of higher sensitivity for central targets than peripheral targets and of misjudging gaze toward peripheral targets as farther from midline than it really was. In subsequent experiments, we evaluated possible reasons for the higher thresholds in 6- and 8-year-olds. In Experiment 2, the thresholds of 6-year-olds did not improve when the range of deviations from the target position that the model fixated covered a much wider range. In Experiment 3, 8-year-olds were less sensitive than adults to small shifts in eye position even though the task required only matching faces with the same eye position and not determining where the person was looking. These findings suggest that by 6 years of age, children are quite sensitive to triadic gaze, which may support inferences about others’ interests and intentions. Subsequent improvements in sensitivity involve, at least in part, an increase in sensitivity to eye position.

Liking and identifying emotionally expressive music: Age and gender differences

Adults and children 5, 8, and 11 years of age listened to short excerpts of unfamiliar music that sounded happy, scary, peaceful, or sad. Listeners initially rated how much they liked each excerpt. They subsequently made a forced-choice judgment about the emotion that each excerpt conveyed. Identification accuracy was higher for young girls than for young boys, but both genders reached adult-like levels by age 11. High-arousal emotions (happiness and fear) were better identified than low-arousal emotions (peacefulness and sadness), and this advantage was exaggerated among younger children. Whereas children of all ages preferred excerpts depicting high-arousal emotions, adults favored excerpts depicting positive emotions (happiness and peacefulness). A preference for positive emotions over negative emotions was also evident among females of all ages. As identification accuracy improved, liking for positively valenced music increased among 5- and 8-year-olds but decreased among 11-year-olds.

Deaf and hearing children: a comparison of peripheral vision development

This study investigated peripheral vision (at least 30° eccentric to fixation) development in profoundly deaf children without cochlear implantation, and compared this to age-matched hearing controls as well as to deaf and hearing adult data. Deaf and hearing children between the ages of 5 and 15 years were assessed using a new, specifically paediatric designed method of static perimetry. The deaf group (N = 25) were 14 females and 11 males, mean age 9.92 years (range 5-15 years). The hearing group (N = 64) were 34 females, 30 males, mean age 9.13 years (range 5-15 years). All participants had good visual acuity in both eyes (< 0.200 LogMAR). Accuracy of detection and reaction time to briefly presented LED stimuli of three light intensities, at eccentricities between 30° and 85° were measured while fixation was maintained to a central target. The study found reduced peripheral vision in deaf children between 5 and 10 years of age. Deaf children (aged 5-10 years) showed slower reaction times to all stimuli and reduced ability to detect and accurately report dim stimuli in the far periphery. Deaf children performed equally to hearing children aged 11-12 years. Deaf adolescents aged 13-15 years demonstrated faster reaction times to all peripheral stimuli in comparison to hearing controls. Adolescent results were consistent with deaf and hearing adult performances wherein deaf adults also showed significantly faster reaction times than hearing controls. Peripheral vision performance on this task was found to reach adult-like levels of maturity in deaf and hearing children, both in reaction time and accuracy of detection at the age of 11-12 years.

The development of luminance- and texture-defined form perception during the school-aged years

The objective of the present study was to assess the development of luminance- and texture-defined static form perception in school-aged children. This was done using an adapted Landolt-C technique where C-optotypes were defined by either luminance or texture information, the latter necessitating extra-striate neural processing to be perceived. Typically developing children were placed in one of 4 school-age groups (6, 8, 10 and 12-year olds); an adult group was also assessed. The contrast threshold for the correct identification of gap-opening-orientation for C-optotypes defined by either texture- or luminance-contrast was measured. All participants were presented with C-optotypes with gap-openings presented in one of 4 orientations (up, down, left or right). An adaptive staircase procedure was used to measure gap-opening-identification thresholds (minimum luminance- or texture-contrast modulation) for all three conditions and ages. As expected, gap-opening identification sensitivity (1/threshold) increased with age for all conditions. For both luminance-defined conditions, adult-like performance was manifested by 12 years of age. By comparison, at 12 years of age, the sensitivity to texture-defined C-optotypes was significantly lower than that of adults, having increased steadily from the age of 6 years. These results suggest that mechanisms underlying static form perception mature at different ages depending on the physical attribute defining the form. Luminance-defined form perception appears to reach adult-like levels (or plateau) earlier than for texture-defined information, suggesting that the development of mechanisms mediating higher-order form perception persist into adolescence.

Acquisition of Adult-Like TLR4 and TLR9 Responses during the First Year of Life

BackgroundCharacteristics of the human neonatal immune system are thought to be responsible for heightened susceptibility to infectious pathogens and poor responses to vaccine antigens. Using cord blood as a source of immune cells, many reports indicate that the response of neonatal monocytes and dendritic cells (DC) to Toll-like receptor (TLR) agonists differs significantly from that of adult cells. Herein, we analyzed the evolution of these responses within the first year of life.Methodology/Principal FindingsBlood samples from children (0, 3, 6, 9, 12 month old) and healthy adults were stimulated ex vivo with bacterial lipopolysaccharide (LPS, TLR4 agonist) or CpG oligonucleotides (TLR9 agonist). We determined phenotypic maturation of monocytes, myeloid (m) and plasmacytoid (p) DC and production of cytokines in the culture supernatants. We observed that surface expression of CD80 and HLA-DR reaches adult levels within the first 3 months of life for mDCs and 6–9 months of life for monocytes and pDCs. In response to LPS, production of TNF-α, IP-10 and IL-12p70 reached adult levels between 6–9 months of life. In response to CpG stimulation, production of type I IFN-dependent chemokines (IP-10 and CXCL9) gradually increased with age but was still limited in 1-year old infants as compared to adult controls. Finally, cord blood samples stimulated with CpG ODN produced large amounts of IL-6, IL-8, IL-1β and IL-10, a situation that was not observed for 3 month-old infants.ConclusionsThe first year of life represents a critical period during which adult-like levels of TLR responses are reached for most but not all cytokine responses.

Development of functional and structural connectivity within the default mode network in young children

Functional and structural maturation of networks comprised of discrete regions is an important aspect of brain development. The default-mode network (DMN) is a prominent network which includes the posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC), medial temporal lobes (MTL), and angular gyrus (AG). Despite increasing interest in DMN function, little is known about its maturation from childhood to adulthood. Here we examine developmental changes in DMN connectivity using a multimodal imaging approach by combining resting-state fMRI, voxel-based morphometry and diffusion tensor imaging-based tractography. We found that the DMN undergoes significant developmental changes in functional and structural connectivity, but these changes are not uniform across all DMN nodes. Convergent structural and functional connectivity analyses suggest that PCC-mPFC connectivity along the cingulum bundle is the most immature link in the DMN of children. Both PCC and mPFC also showed gray matter volume differences, as well as prominent macrostructural and microstructural differences in the dorsal cingulum bundle linking these regions. Notably, structural connectivity between PCC and left MTL was either weak or non-existent in children, even though functional connectivity did not differ from that of adults. These results imply that functional connectivity in children can reach adult-like levels despite weak structural connectivity. We propose that maturation of PCC-mPFC structural connectivity plays an important role in the development of self-related and social-cognitive functions that emerge during adolescence. More generally, our study demonstrates how quantitative multimodal analysis of anatomy and connectivity allows us to better characterize the heterogeneous development and maturation of brain networks.

Postnatal Development of an Estradiol-Kisspeptin Positive Feedback Mechanism Implicated in Puberty Onset

The regulation of GnRH neurons by kisspeptin is critical for normal puberty onset in mammals. In the rodent the kisspeptin neurons innervating GnRH neurons are thought to reside in the rostral periventricular area of the third ventricle (RP3V). Using kisspeptin immunocytochemistry we show that kisspeptin peptide expression in the RP3V of female mice begins around postnatal d 15 (P15) and rapidly increases to achieve adult-like levels by P30, the time of puberty onset. Ovariectomy of female pups at P15 resulted in a 70-90% reduction (P < 0.01) in kisspeptin peptide expression within the RP3V of P30 or P60 mice. Replacement of 17-beta-estradiol (E2) in P15-ovariectomized mice from P15-30 or P22-30 resulted in a complete restoration of kisspeptin peptide expression in the RP3V (P < 0.01). Kisspeptin-immunoreactive fibers throughout the hypothalamus, including the arcuate nucleus, followed the same pattern of estrogen-dependent expression. To test the absolute necessity of estrogen for kisspeptin expression in the RP3V, aromatase knockout mice were examined. Kisspeptin-immunoreactive cells were detected in the arcuate nucleus, but there was a complete absence of kisspeptin peptide in RP3V neurons of aromatase knockout adult females. These results demonstrate that E2 is essential for the prepubertal development of kisspeptin peptide within RP3V neurons and suggest that an E2-kisspeptin positive feedback mechanism exists before puberty. This implies that RP3V kisspeptin neurons are E2-dependent amplifiers of GnRH neuron activity in the prepubertal period.

Cues for the control of ocular accommodation and vergence during postnatal human development

Accommodation and vergence help maintain single and focused visual experience while an object moves in depth. The relative importance of retinal blur and disparity, the primary sensory cues to accommodation and vergence, is largely unknown during development; a period when growth of the eye and head necessitate continual recalibration of egocentric space. Here we measured the developmental importance of retinal disparity in 192 typically developing subjects (1.9 months to 46 years). Subjects viewed high-contrast cartoon targets with naturalistic spatial frequency spectra while their accommodation and vergence responses were measured from both eyes using a PowerRefractor. Accommodative gain was reduced during monocular viewing relative to full binocular viewing, even though the fixating eye generated comparable tracking eye movements in the two conditions. This result was consistent across three forms of monocular occlusion. The accommodative gain was lowest in infants and only reached adult levels by 7 to 10 years of age. As expected, the gain of vergence was also reduced in monocular conditions. When 4- to 6-year-old children read 20/40-sized letters, their monocular accommodative gain reached adult-like levels. In summary, binocular viewing appears necessary under naturalistic viewing conditions to generate full accommodation and vergence responses in typically developing humans.

The development of implicit intergroup cognition

Challenging the view that implicit social cognition emerges from protracted social learning, research now suggests that intergroup preferences are present at adultlike levels in early childhood. Specifically, the pattern of developmental emergence of implicit attitudes is characterized by (i) rapidly emerging implicit preferences for ingroups and dominant groups and (ii) stability of these preferences across development. Together these findings demonstrate that implicit intergroup preferences follow a developmental course distinct from explicit intergroup preferences. In addition these results cast doubt on 'slow-learning' models of implicit social cognition according to which children should converge on adult forms of social cognition only as statistical regularities are internalized over a lengthy period of development.