Cognitive Function In Infants Research Articles

Shh activation restores interneurons and cognitive function in newborns with intraventricular haemorrhage.

Premature infants with germinal matrix haemorrhage-intraventricular haemorrhage (GMH-IVH) suffer from neurobehavioural deficits as they enter childhood and adolescence. Yet the underlying mechanisms remain unclear. Impaired development and function of interneurons contribute to neuropsychiatric disorders. Therefore, we hypothesized that the occurrence of IVH would reduce interneuron neurogenesis in the medial ganglionic eminence and diminish the population of parvalbumin+ and somatostatin+ cortical interneurons. Because Sonic Hedgehog promotes the production of cortical interneurons, we also postulated that the activation of Sonic Hedgehog signalling might restore neurogenesis, cortical interneuron population, and neurobehavioural function in premature newborns with IVH. These hypotheses were tested in a preterm rabbit model of IVH and autopsy samples from human preterm infants. We compared premature newborns with and without IVH for intraneuronal progenitors, cortical interneurons, transcription factors regulating neurogenesis, single-cell transcriptome of medial ganglionic eminence and neurobehavioural functions. We treated premature rabbit kits with adenovirus expressing Sonic Hedgehog (Ad-Shh) or green fluorescence protein gene to determine the effect of Sonic Hedgehog activation on the interneuron production, cortical interneuron population and neurobehaviour. We discovered that IVH reduced the number of Nkx2.1+ and Dlx2+ progenitors in the medial ganglionic eminence of both humans and rabbits by attenuating their proliferation and inducing apoptosis. Moreover, IVH decreased the population of parvalbumin+ and somatostatin+ neurons in the frontal cortex of both preterm infants and kits relative to controls. Sonic Hedgehog expression and the downstream transcription factors, including Nkx2.1, Mash1, Lhx6 and Sox6, were also reduced in kits with IVH. Consistent with these findings, single-cell transcriptomic analyses of medial ganglionic eminence identified a distinct subpopulation of cells exhibiting perturbation in genes regulating neurogenesis, ciliogenesis, mitochondrial function and MAPK signalling in rabbits with IVH. More importantly, restoration of Sonic Hedgehog level by Ad-Shh treatment ameliorated neurogenesis, cortical interneuron population and neurobehavioural function in kits with IVH. Additionally, Sonic Hedgehog activation alleviated IVH-induced inflammation and several transcriptomic changes in the medial ganglionic eminence. Taken together, IVH reduced intraneuronal production and cortical interneuron population by downregulating Sonic Hedgehog signalling in both preterm rabbits and humans. Notably, activation of Sonic Hedgehog signalling restored interneuron neurogenesis, cortical interneurons and cognitive function in rabbit kits with IVH. These findings highlight disruption in cortical interneurons in IVH and identify a novel therapeutic strategy to restore cortical interneurons and cognitive function in infants with IVH. These studies can accelerate the development of new therapies to enhance the neurodevelopmental outcome of survivors with IVH.

Characterization of milk and soy phospholipid liposomes and inflammation in 3T3-L1 adipocytes

Milk phospholipids (PL) are valuable dairy components that appear to impart human health benefits, including improved cognitive function in infants and adults. The commercial food industry uses primarily plant-based sources of PL, such as soy lecithin. However, it remains unclear whether different compositions of PL from different dietary sources, such as milk, convey the same benefits. We hypothesized that PL derived from bovine milk or soy have differing physiological effects in terms of inflammation due to their differences in composition. The objectives of this study were to characterize milk and soy liposomes by their physicochemical properties and composition and to evaluate their effects in vitro by means of inflammatory gene expression analyses. Milk and soy phospholipid large unilamellar vesicles (MPL-LUV and SPL-LUV, respectively) prepared using thin-film hydration coupled with extrusion were similar in terms of structure, size, and stability; however, they differed significantly in composition. The 3T3-L1 adipocytes were selected for this work because adipocytes are the main site of uptake, synthesis, modification, and breakdown of lipids and are important inflammatory mediators in mammalian systems. In this work, these cells exposed to both liposome varieties showed high biocompatibility and low cytotoxicity up to concentrations of 0.5 mg/mL as measured by colorimetric MTT and lactate dehydrogenase assays. Furthermore, SPL-LUV showed trends toward stimulating inflammation compared with MPL-LUV as measured by expression of 2 proinflammatory cytokines, monocyte chemoattractant protein-1 (MCP-1) and IL-6. Expression of MCP-1 significantly increased 1.82-fold relative to the control upon SPL-LUV treatment, with similar trends for IL-6 (increased 1.59-fold). The MPL-LUV showed relatively no change in cytokine expression. The results obtained in this work suggest that the methodology used to prepare LUV and the composition and proportion of milk PL are important in measuring cell physiology changes and inflammatory status in mammalian cells.

Predictive Validity of the Bayley-III Cognitive Scores at 6 Months for Cognitive Outcomes at 24 Months in Very-Low-Birth-Weight Infants.

Purpose: To assess the predictive validity of the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) cognitive scores at 6 months of corrected age (CA) for cognitive outcomes at 24 months of CA in very-low-birth-weight (VLBW) infants and investigate the predictors of change in cognitive outcomes.Methods: We retrospectively evaluated VLBW children enrolled in the Taiwan Premature Infant Follow-up Network between 2010 and 2015 and completed the Bayley-III at CA of 6 and 24 months. The predictive validity of the cognitive performance at 6-month CA for the cognitive outcomes at 24-month CA was analyzed. The positive and negative predictive factors were also evaluated using logistic regression. Cut-off scores of <70 and <85 were used to identify lower functioning groups based on the Bayley-III definition.Results: A total of 2,972 VLBW children, born with a mean weight of 1116.4 ± 257.5 g and mean gestational age of 29.0 ± 2.8 weeks, were evaluated. A cognitive score of <70 at 6-month CA had a positive predictive value (PPV) of 27.4% (95% confidence interval [CI]: 19.2–35.7%) for a cognitive score of <70 at 24-month CA, while the negative predictive value (NPV) was 97.3% (95% CI: 96.7–97.9%). A cut-off score of 85 had a PPV of 33.6% (95% CI: 28.1–39.0%) and an NPV of 87.7% (95% CI: 86.4–88.9%). Abnormal muscle tone at 6 months was a risk factor for cognitive function decline at 24 months for both Bayley-III cognitive cut-off scores: scores of 70 (adjusted odds ratio [AOR]: 2.8; 95% CI: 1.5–5.5) and 85 (AOR: 2.6; 95% CI: 1.6–4.1). Lower maternal socioeconomic status was associated with a worsening of the cognitive function in infants at 24 months who scored ≥85 at 6 months (AOR: 1.6; 95% CI: 1.2–2.0).Conclusion: Subnormal Bayley-III cognitive scores at 6-month CA were not predictive of subnormal cognitive function at 24-month CA. In children with normal cognition during early infancy, abnormal muscle tone and lower maternal socioeconomic status may influence the cognitive developing process; this highlighted the importance of early identification of high risk infants and complete preterm infant-associated public health policies to promote an improved neurodevelopmental outcome.

Nutritional Support of Neurodevelopment and Cognitive Function in Infants and Young Children-An Update and Novel Insights.

Proper nutrition is crucial for normal brain and neurocognitive development. Failure to optimize neurodevelopment early in life can have profound long-term implications for both mental health and quality of life. Although the first 1000 days of life represent the most critical period of neurodevelopment, the central and peripheral nervous systems continue to develop and change throughout life. All this time, development and functioning depend on many factors, including adequate nutrition. In this review, we outline the role of nutrients in cognitive, emotional, and neural development in infants and young children with special attention to the emerging roles of polar lipids and high quality (available) protein. Furthermore, we discuss the dynamic nature of the gut-brain axis and the importance of microbial diversity in relation to a variety of outcomes, including brain maturation/function and behavior are discussed. Finally, the promising therapeutic potential of psychobiotics to modify gut microbial ecology in order to improve mental well-being is presented. Here, we show that the individual contribution of nutrients, their interaction with other micro- and macronutrients and the way in which they are organized in the food matrix are of crucial importance for normal neurocognitive development.

Prenatal sevoflurane exposure: Effects of iron metabolic dysfunction on offspring cognition and potential mechanism.

For decades, the neurotoxicity caused by anesthetics in mammalian brain development has gained increasing attention. Exposure to anesthetics leads to neurotoxicity and apoptosis of nerve cells, which in turn induces cognitive dysfunction. Although most of the data came from animal studies, general anesthetics have been shown to have adverse effects on cognitive function in infants and young children in recent years. This concern has led to a number of retrospective studies that observed an association between general anesthesia in pregnant women and neurobehavioral problems in fetuses or offspring. Every year, many pregnant women undergo non-obstetric anesthesia due to various reasons such as traffic accidents, fetal interventions, acute appendicitis, symptomatic cholelithiasis, and trauma. A matter of concern for these pregnant women is whether anesthesia has a detrimental effect on fetal brain development in the womb and whether the fetus has cognitive impairment after birth. In humans, the association of anesthetic exposure in infants with the long-term impairment of neurologic functions has been reported in several retrospective clinical studies. Recently, we have found that sevoflurane anesthesia during pregnancy in mice-induced cognitive impairment in the offspring by causing iron deficiency and inhibiting myelinogenesis. Sevoflurane is a commonly used general anesthetic in the hospitals, which can induce neurotoxicity and cause cognitive impairment in fetuses, infants, children, and adults. However, the exact mechanism of sevoflurane-induced damage to the central nervous system (CNS) is not fully understood. Based on our recent results, this paper reviewed the effects of sevoflurane on cognitive impairment and pathological changes such as neurogenesis, neuronal apoptosis, and iron metabolism dysfunction in the offspring.

The Effect of Independent Robotic Mobility on Infant Cognitive Skills

Abstract Date Presented 04/04/19 Researchers hypothesize that independent mobility affects the development of cognitive function in infants and young children. In our experimental research, typically developing precrawling infants were randomly assigned to a robotic mobility or a nonmobile condition. Preliminary results showed that limited experience with independent mobility significantly impacted cognitive development in the mobility group, supporting the need for early mobility aids for infants with motor impairment. Primary Author and Speaker: Carole Dennis Contributing Authors: Nancy Rader, Sharon Stansfield, Hélène Larin, Judith Pena-Shaff

Functional near infrared spectroscopy (fNIRS) to assess cognitive function in infants in rural Africa.

Cortical mapping of cognitive function during infancy is poorly understood in low-income countries due to the lack of transportable neuroimaging methods. We have successfully piloted functional near infrared spectroscopy (fNIRS) as a neuroimaging tool in rural Gambia. Four-to-eight month old infants watched videos of Gambian adults perform social movements, while haemodynamic responses were recorded using fNIRS. We found distinct regions of the posterior superior temporal and inferior frontal cortex that evidenced either visual-social activation or vocally selective activation (vocal > non-vocal). The patterns of selective cortical activation in Gambian infants replicated those observed within similar aged infants in the UK. These are the first reported data on the measurement of localized functional brain activity in young infants in Africa and demonstrate the potential that fNIRS offers for field-based neuroimaging research of cognitive function in resource-poor rural communities.

Optical imaging of brain activation in Gambian infants.

We used optical topography (OT) to investigate cognitive function in infants in rural Gambia. Images of changes in oxyhaemoglobin and deoxyhaemoglobin concentrations were reconstructed using a multispectral algorithm which uses the finite element method (FEM) to model the propagation of light through scattering tissue using the diffusion equation. High quality OT data enabled us to reconstruct images with robust representation of haemodynamic changes. OT is a feasible neuroimage technology for this resource-poor setting.

Visual cognitive function in infants with intractable epilepsy before and after surgery

One purpose of pediatric epilepsy surgery is to improve psychomotor development. However, few methods are available for evaluating cognitive function in infants with severe developmental delays. We used the following battery of tests to evaluate visual cognitive function of infants following surgery for intractable epilepsy. The following battery of tests were used to evaluate eight patients before and 1 month after surgery: (1) Erhardt Developmental Vision Assessment (EDVA); (2) evaluation of ocular pursuit for a flashing LED toy; (3) three visual acuity tests preferential looking procedure, optokinetic nystagmus, and Sheridan's Test for Young Children and Retarded balls vision test; and (4) existing developmental test. EDVA scores and ocular pursuit score with a flashing LED toy showed the same trends with developmental age as the existing developmental tests. However, in some patients, the EDVA score and ocular pursuit score improved greatly, whereas the developmental age changed very little. These tests are suitable for patients with intractable epilepsy and severe developmental delay. By performing these tests before and after surgery, small cognitive changes occurring soon after the surgery may be detected.

LPIAT1 regulates arachidonic acid content in phosphatidylinositol and is required for cortical lamination in mice

Dietary arachidonic acid (AA) has roles in growth, neuronal development, and cognitive function in infants. AA is remarkably enriched in phosphatidylinositol (PI), an important constituent of biological membranes in mammals; however, the physiological significance of AA-containing PI remains unknown. In an RNA interference-based genetic screen using Caenorhabditis elegans, we recently cloned mboa-7 as an acyltransferase that selectively incorporates AA into PI. Here we show that lysophosphatidylinositol acyltransferase 1 (LPIAT1, also known as MBOAT7), the closest mammalian homologue, plays a crucial role in brain development in mice. Lpiat1(-/-) mice show almost no LPIAT activity with arachidonoyl-CoA as an acyl donor and show reduced AA contents in PI and PI phosphates. Lpiat1(-/-) mice die within a month and show atrophy of the cerebral cortex and hippocampus. Immunohistochemical analysis reveals disordered cortical lamination and delayed neuronal migration in the cortex of E18.5 Lpiat1(-/-) mice. LPIAT1 deficiency also causes disordered neuronal processes in the cortex and reduced neurite outgrowth in vitro. Taken together, these results demonstrate that AA-containing PI/PI phosphates play an important role in normal cortical lamination during brain development in mice.

The Changing Yardstick in Measurement of Cognitive Abilities in Infancy

There are concerns regarding accurate measurement of cognitive function in infants, particularly those at biologic risk. Herein we discuss these issues and make recommendations. Concerns include: 1) secular changes in test norms, referred to as the Flynn effect; 2) changes in the content of revised test versions; 3) recent findings of higher mean scores in newer test versions when compared to previous scores; and 4) correction for prematurity. Caution is necessary when comparing the same test scores over extended periods of time, and using different versions of the same test when mean scores of the tests vary or evaluate different areas of functioning. Ideal solutions are not readily apparent and thus we provide several suggestions: control groups are essential for longitudinal studies; clinicians should not rely totally on cognitive scores; and further investigation of the Flynn effect in different subgroups of children at different ages is necessary.

Docosahexaenoic acid: Measurements in food and dietary exposure

The Dietary Reference Intakes (DRIs) were established to be an indicator of adequacy of dietary nutrients as well as providing levels for adequacy in reducing risk of chronic diseases such as neurodegenerative diseases, cardiovascular diseases, cancers, diabetes mellitus, etc. One particular nutrient that is increasingly discussed as a potential candidate for the generation of a DRI is the omega-3 (n-3) fatty acid docosahexaenoic acid (DHA) due to its potential benefits in reducing risk for cardiovascular disease, role in resolution of inflammation, its importance in cognitive function in infants and inhibiting the progression of neurodegenerative diseases in the elderly. Each reference value refers to and is predicated on estimates of daily nutrient intake and the goal of this paper is to review these intakes. The confidence of these values is critical in establishing dose–response relationships. This paper reports intake values for DHA and examines how these data were generated and the relative confidence in these values. The adult US population is estimated to consume 80–100 mg/d of DHA based on a nationally representative sample of >8400 individuals as part of the National Health and Nutrition Examination Survey (NHANES). This value and those presented for women and men at various ages appear reasonable and should be used as the basis for establishing an Adequate Intake (AI) for DHA.

Iron Feeds the Brain as Well as the Blood

Numerous studies have demonstrated the deleterious effects of iron deficiency on cognitive function in infants and children, but data on the effects in adolescents and women of reproductive age are scarce. In a double-blind, placebo-controlled study, investigators at The Pennsylvania State University stratified 152 women (age range, 18–35; mean age, 21) according to iron status and randomly assigned them to receive a slow- release iron supplement or placebo for 16 …

The effects of iron supplementation on cognitive function in infants and children.

The effects of iron supplementation on cognitive function in infants and children.

Comparison of infant and adult P300 from auditory stimuli

Event-related brain potentials (ERPs) using auditory stimuli were recorded from 5- to 10-month-old infants and normal young adults with a passive tone sequence paradigm. A P3 (P300) component was obtained which demonstrated the same central-parietal maximum scalp distribution for both subject groups. P3 amplitude was smaller and its peak latency longer for infants compared to those of the adults across all electrode sites. P3 measures remained stable across stimulus trials indicating that ERP habituation was not occurring. Evaluation of individual subjects suggests that the P3 can be elicited from infants with auditory stimuli in a manner similar to that from adults and may serve as a useful index for the assessment of cognitive function in infants.

Anticonvulsant Therapy After Neonatal Seizures—How Long Should it Be Continued?

The risk of epilepsy or afebrile seizures after convulsions in the neonatal period is compared with the benefits and risks of chronic use of anticonvulsants in infants. The best predictor of later seizures appears to be the presence of moderate to severe neurologic damage. In the absence of such deficits, the risk is below 10%, but increases to 50-70% when damage is severe. A comparison of reports indicates no difference in seizure recurrence rates when anticonvulsants are stopped early in the neonatal period or when treatment is longer, even in the high-risk group. After phenobarbital is discontinued and the plasma concentration falls below the therapeutic range, seizures usually recur within a few days or not for several months. Only 50% of these seizure types are expected to be controlled with phenobarbital. Long-term phenobarbital use is associated with impaired cognitive function in infants and toddlers, and retarded brain growth in rodent studies.