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Biomedical subjects

C A Nelson

Publications and source records attributed to C A Nelson.

At least 19 recordsLinked to original sources
PubMed2005

Plasticity of face processing in infancy.

Experience plays a crucial role for the normal development of many perceptual and cognitive functions, such as speech perception. For example, between 6 and 10 months of age, the infant's ability to discriminate among native speech sounds improves, whereas the ability to discriminate among foreign speech sounds declines. However, a recent investigation suggests that some experience with non-native languages from 9 months of age facilitates the maintenance of this ability at 12 months. Nelson has suggested that the systems underlying face processing may be similarly sculpted by experience with different kinds of faces. In the current investigation, we demonstrate that, in human infants between 6 and 9 months of age, exposure to non-native faces, in this case, faces of Barbary macaques (Macaca sylvanus), facilitates the discrimination of monkey faces, an ability that is otherwise lost around 9 months of age. These data support, and further elucidate, the role of early experience in the development of face processing.

Animals↗
PubMed2001

Direct detection of a microlens in the Milky Way.

The nature of dark matter remains mysterious, with luminous material accounting for at most approximately 25 per cent of the baryons in the Universe. We accordingly undertook a survey looking for the microlensing of stars in the Large Magellanic Cloud (LMC) to determine the fraction of Galactic dark matter contained in massive compact halo objects (MACHOs). The presence of the dark matter would be revealed by gravitational lensing of the light from an LMC star as the foreground dark matter moves across the line of sight. The duration of the lensing event is the key observable parameter, but gives non-unique solutions when attempting to estimate the mass, distance and transverse velocity of the lens. The survey results to date indicate that between 8 and 50 per cent of the baryonic mass of the Galactic halo is in the form of MACHOs (ref. 3), but removing the degeneracy by identifying a lensing object would tighten the constraints on the mass in MACHOs. Here we report a direct image of a microlens, revealing it to be a nearby low-mass star in the disk of the Milky Way. This is consistent with the expected frequency of nearby stars acting as lenses, and demonstrates a direct determination of a lens mass from a microlensing event. Complete solutions such as this for halo microlensing events will probe directly the nature of the MACHOs.

Journal Article↗
PubMed2001

Structural and functional consequences of altering a peptide MHC anchor residue.

To better understand TCR discrimination of multiple ligands, we have analyzed the crystal structures of two Hb peptide/I-E(k) complexes that differ by only a single amino acid substitution at the P6 anchor position within the peptide (E73D). Detailed comparison of multiple independently determined structures at 1.9 A resolution reveals that removal of a single buried methylene group can alter a critical portion of the TCR recognition surface. Significant variance was observed in the peptide P5-P8 main chain as well as a rotamer difference at LeuP8, approximately 10 A distal from the substitution. No significant variations were observed in the conformation of the two MHC class II molecules. The ligand alteration results in two peptide/MHC complexes that generate bulk T cell responses that are distinct and essentially nonoverlapping. For the Hb-specific T cell 3.L2, substitution reduces the potency of the ligand 1000-fold. Soluble 3.L2 TCR binds the two peptide/MHC complexes with similar affinity, although with faster kinetics. These results highlight the role of subtle variations in MHC Ag presentation on T cell activation and signaling.

Amino Acid Sequence↗
PubMed2001

Perceptual priming for upright and inverted faces in infants and adults.

Based on recent models of the ontogeny of memory (Nelson, 1995), we hypothesize that 6-month-old infants should show evidence of repetition priming. Event-related potentials were recorded from 11 scalp sites to novel and primed upright and inverted faces. In Experiment 1 (n = 24), 6-month-old infants viewed faces that were repeated after 6 to 12 images. Overall, repeated faces demonstrated greater negativity than novel faces and upright faces demonstrated greater negativity than inverted faces. In order to ground these results in an adult model, a group of adults (n = 30) was tested in a similar experiment. Here we observed effects of repetition at an early positive component labeled the P150 as well as at the P300, with repeated images being more positive than novel images. These data support the idea that infants at 6 months are capable of revealing electrophysiological evidence of perceptual priming.

Adolescent↗
PubMed2001

Serial reaction time learning in preschool- and school-age children.

Visuomotor sequence learning was assessed in 4- to 10-year-old children using a serial reaction time (SRT) task with both random and sequenced trials. One-half of the children received exposure to the sequence prior to performing the reaction time (RT) task. In Experiment 1, 7- and 10-year-old children demonstrated sequence-specific decreases in RT. As in the adult SRT literature, participants with explicit awareness of the sequence at the end of the session showed larger sequence-specific reaction time decrements than those without explicit awareness. Contrary to expectation, preexposure to the sequence did not reliably predict the level of awareness attained. Results from Experiment 2 indicate that 4-year-olds also demonstrate significant sequence learning on a variant of the SRT task. This article provides preliminary data regarding developmental changes in sequential learning and the development and use of implicit and explicit knowledge. Age-related differences emerged primarily in explicit rather than implicit knowledge.

Age Factors↗
PubMed2001

The development of face expertise.

Recent neuroimaging studies in adults indicate that visual areas selective for recognition of faces can be recruited through expertise for nonface objects. This reflects a new emphasis on experience in theories of visual specialization. In addition, novel work infers differences between categories of nonface objects, allowing a re-interpretation of differences seen between recognition of faces and objects. Whether there are experience-independent precursors of face expertise remains unclear; indeed, parallels between literature for infants and adults suggest that methodological issues need to be addressed before strong conclusions can be drawn regarding the origins of face recognition.

Adult↗
PubMed2001

Neural bases and development of face recognition in autism.

This paper critically examines the literature on face recognition in autism, including a discussion of the neural correlates of this ability. The authors begin by selectively reviewing the behavioral and cognitive neuroscience research on whether faces are represented by a "special" behavioral and neural system-one distinct from object processing. The authors then offer a neuroconstructivist model that attempts to account for the robust finding that certain regions in the inferior temporal cortex are recruited in the service of face recognition. This is followed by a review of the evidence supporting the view that face recognition is atypical in individuals with autism. This face-recognition deficit may indicate a continued risk for the further development of social impairments. The authors conclude by speculating on the role of experience in contributing to this atypical developmental pattern and its implications for normal development of face processing.

Journal Article↗
PubMed2001

Developmental science and the media. Early brain development.

Media coverage of early brain development not only has focused public attention on early childhood but also has contributed to misunderstanding of developmental neuroscience research. This article critically summarizes current research in developmental neuroscience that is pertinent to the central claims of media accounts of early brain development, including (a) scientific understanding of formative early experiences, (b) whether critical periods are typical for brain development, (c) brain development as a lifelong process, (d) biological hazards to early brain growth, and (e) strengths and limits of current technology in developmental brain research. Recommendations are offered for strengthening the constructive contributions of research scientists and their professional organizations to the accurate and timely coverage of scientific issues in the media.

Brain↗
PubMed2001

Crystal structure of the TRANCE/RANKL cytokine reveals determinants of receptor-ligand specificity.

RANK, the receptor activator of NF-kappaB, and its ligand RANKL (initially termed TRANCE, also termed ODF and OPGL), are a TNF superfamily receptor-ligand pair that govern the development and function of osteoclasts, lymphoid tissue, and mammary epithelium. While TNF family cytokines share a common structural scaffold, individual receptor-ligand pairs associate with high specificity. Given the low level of amino acid conservation among members of the TNF superfamily, the means by which these molecules achieve specificity cannot be completely understood without knowledge of their three-dimensional structures. To determine the elements of RANKL that mediate RANK activation, we have crystallized the ectodomain of murine RANKL and solved its structure to a resolution of 2.6 A. RANKL self-associates as a homotrimer with four unique surface loops that distinguish it from other TNF family cytokines. Mutagenesis of selected residues in these loops significantly modulates RANK activation, as evidenced by in vitro osteoclastogenesis, thereby establishing their necessity in mediating the biological activities of RANKL. Such structural determinants of RANKL-RANK specificity may be of relevance in the pharmacologic design of compounds to ameliorate osteopenic disorders of bone.

Animals↗
PubMed2001

Mechanisms of postnatal neurobiological development: implications for human development.

This review focuses on the postnatal neuroanatomical changes that arise during the first years of human life. Development is characterized by 2 major organizational periods. The first period begins at conception and includes the major histogenetic events such as neurulation, proliferation, migration, and differentiation. It has been proposed that these events may be controlled by genetic and epigenetic events, which give rise to neural structures that are amenable to external influence. The second period is a time of reorganization in the human cortex. These events occur during gestation and continue postnatally, possibly through the 2nd decade of life. This stage is characterized by dendritic and axonal growth, synapse production, neuronal and synaptic pruning, and changes in neurotransmitter sensitivity. Although the initiation of these events is influenced by endogenous signals, further neural maturation is primarily influenced by exogenous signals. To illustrate both the progressive and regressive events during the postnatal period, we use examples from the development of the human cortex.

Axons↗
PubMed2001

Prenatal neurobiological development: molecular mechanisms and anatomical change.

During prenatal development, the central nervous system is transformed from a thin layer of unspecified tissue into a complex system that can process information and organize actions. There are 8 general mechanisms that permit this transformation: neural induction, neurulation, proliferation, migration, axonal outgrowth, synaptogenesis, differentiation, and apoptosis. These processes as well as the anatomical changes they cause are described. Future research with humans, such as in utero MRI as well as behavioral and electrophysiological testing of infants following specific prenatal perturbations, is suggested to link the findings from molecular approaches to developmental neuropsychology.

Apoptosis↗
PubMed2000

Hb(64-76) epitope binds in different registers and lengths to I-Ek and I-Ak.

The nature of peptide binding to MHC molecules is intrinsically degenerate, in what, one given MHC molecule can accommodate numerous peptides which are structurally diverse, and one given peptide can bind to different alleles. The structure of the MHC class II molecules allows peptides to extend out of the binding groove at both ends and these residues can potentially influence the stability and persistence of peptide/class II complexes. We have previously shown that both I-E(k) and I-A(k)-restricted T cell hybridomas could be generated against the Hb(64-76) epitope. In this study, we characterized the binding register of the Hb(64-76) epitope to I-A(k), and showed that it was shifted by one residue in comparison to its binding to I-E(k), and did not use a dominant anchor residue at P1. This conclusion was further supported by the modeling of the Hb(64-76) epitope bound to I-A(k), which revealed that all of its putative anchor residues fit into their corresponding pockets. We identified the naturally processed Hb epitopes presented by both I-E(k) and I-A(k), and found that they consisted of different species. Those associated with I-A(k) being 20-22 residues long, whereas, those found to I-E(k) contained 14-16 residues. These findings suggested that the lack of a dominant P1 anchor could be compensated by the selection of longer peptides. Overall, these studies revealed the Hb(64-76) epitope bound to I-E(k) and I-A(k) in distinct registers and lengths, demonstrating the plasticity MHC molecules have in generating distinct TCR ligands from the same amino acid sequence.

Antigen Presentation↗
PubMed2000

Effects of inter-item lag on recognition memory in seizure patients preceding temporal lobe resection: evidence from event-related potentials.

The electrophysiological correlates of word recognition are well characterized. Repeated 'old' words evoke a more positive-going waveform starting at approximately 300 ms compared with first-presented, 'new' words. The old/new effect is thought to be generated, in part, by structures within the medial temporal lobe. In the present study, event-related potentials were recorded during a continuous verbal recognition memory task in unoperated patients with either left (L) or right (R) unilateral temporal lobe epilepsy (Epil) and neurologically intact controls. To manipulate the difficulty of the memory task, the lag between the initial and subsequent presentation of the repeated words was varied from one, four to 16 items. In the controls, ERPs to old words were more positive going than new words from approximately 350-650 ms. The old/new effect diminished as the inter-item lag increased. Patient old/new effects showed a later onset (450 ms) and resolution (750 ms) compared with the controls. Furthermore, the late component of the old/new effect was significantly reduced in the L Epil. Although patient behavioral performance did not differ significantly from that of the controls, neuropsychological testing revealed impaired verbal memory function in the L Epil patients. It is concluded that the reduced old/new effect in the L Epil patients provides evidence that medial temporal lobe structures contribute to the scalp-recorded old/new effect.

Adolescent↗
PubMed2000

Structural basis of peptide binding and presentation by the type I diabetes-associated MHC class II molecule of NOD mice.

We have determined the crystal structure of I-Ag7, an integral component in murine type I diabetes development. Several features distinguish I-Ag7 from other non-autoimmune-associated MHC class II molecules, including novel peptide and heterodimer pairing interactions. The binding groove of I-Ag7 is unusual at both terminal ends, with a potentially solvent-exposed channel at the base of the P1 pocket and a widened entrance to the P9 pocket. Peptide binding studies with variants of the hen egg lysozyme I-Ag7 epitope HEL(11-25) support a comprehensive structure-based I-Ag7 binding motif. Residues critical for T cell recognition were investigated with a panel of HEL(11-25)-restricted clones, which uncovered P1 anchor-dependent structural variations. These results establish a framework for future experiments directed at understanding the role of I-Ag7 in autoimmunity.

Amino Acid Sequence↗
PubMed2000

Explicit memory in low-risk infants aged 19 months born between 27 and 42 weeks of gestation.

The aim of this study was to determine whether there are primary effects of prematurity on the development of explicit memory. Elicited imitation of action sequences was used to compare immediate and 15-minute delayed memory in term and preterm infants (19 months corrected age; n=48) who were at low risk: none had experienced the medical or social risk factors often associated with preterm birth. Relative to infants born at term (38 to 40 weeks' gestation), children who had been born at 27 to 34 weeks' gestation showed lower levels of ordered recall; performance of healthy infants born at 35 to 37 weeks' gestation was intermediate and did not differ significantly from that of the other groups. These results suggest that specific cognitive deficits can occur as a function of preterm birth even in low-risk infants.

Cognition Disorders↗
PubMed2000

Functional neuroanatomy of spatial working memory in children.

Functional magnetic resonance imaging (fMRI) was used to examine spatial working memory in 8- to 11-year-old children tested under three conditions. In the visual condition, children were asked to examine the location of a dot on a screen. In the motor condition, children were instructed to push a button that corresponded to the location of a dot presented on a screen. In the memory condition, children were asked to remember the location of a dot presented 1 or 2 trials previously. Subtracting the activation of the motor condition from the memory condition revealed activity in the dorsal aspects of the prefrontal cortex and in the posterior parietal and anterior cingulate cortex. These findings were also obtained in the analysis of the memory minus visual conditions except that motor cortex activation was also observed. These findings parallel those reported in comparable studies of adults and suggest that fMRI may be a useful means of examining function-structure relations in developmental populations.

Adult↗
PubMed2000

Neurophysiologic evaluation of auditory recognition memory in healthy newborn infants and infants of diabetic mothers.

OBJECTIVES: We evaluated the integrity of neural pathways for auditory recognition memory in normal newborn infants (n = 32) and infants of diabetic mothers (IDMs, n = 25). IDMs are at risk for fetal metabolic abnormalities that potentially damage recognition memory pathways. We hypothesized that newborn IDMs would have recognition memory deficits that would be correlated with later cognitive development. STUDY DESIGN: Recognition memory was assessed with event-related potentials (ERPs). Neonatal ERPs elicited by the maternal voice were compared with those elicited by a stranger's voice. The Bayley Scales of Infant Development were administered at 1 year of age. RESULTS: Infants in both the control and IDM groups demonstrated recognition of the maternal voice, but their ERP patterns differed. Both groups demonstrated increased amplitude and latency for the "P2" peak elicited by the maternal voice compared with the stranger's voice. In the control group the stranger's voice also elicited a negative slow wave, which was attenuated in the IDMs. The negative slow wave correlated significantly with the 1-year Mental Developmental Index. CONCLUSIONS: The presence of a specific neonatal ERP pattern indicated better 1-year cognitive development in infants in the control and IDM groups. ERPs from IDMs demonstrated subtle evidence of recognition memory impairments.

Analysis of Variance↗