Shaping the Developing Brain: 5th Annual Aspen Brain Forum

Journal Articles

How will we map neurodevelopment?

Gulsuner S, Walsh T, Watts AC, et al. Spatial and temporal mapping of de novo mutations in schizophrenia to a fetal prefrontal cortical network. Cell. 2013;154(3):518-29.

Gur RC, Richard J, Calkins ME, et al. Age group and sex differences in performance on a computerized neurocognitive battery in children age 8–21. Neuropsychology. 2012;26(2):251-65.

Mariani J, Simonini MV, Palejev D, et al. Modeling human cortical development in vitro using induced pluripotent stem cells. Proc Natl Acad Sci U S A. 2012;109(31):12770-5.

Miller JA, Ding SL, Sunkin SM, et al. Transcriptional landscape of the prenatal human brain. Nature. 2014;508(7495):199-206.

Paşca SP, Portmann T, Voineagu I, et al. Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome. Nat Med. 2011;17(12):1657-62.

Roalf DR, Gur RE, Ruparel K, et al. Within-individual variability in neurocognitive performance: age- and sex-related differences in children and youths from ages 8 to 21. Neuropsychology. 2014;28(4):506-18.

Sheridan SD, Theriault KM, Reis SA, et al. Epigenetic characterization of the FMR1 gene and aberrant neurodevelopment in human induced pluripotent stem cell models of fragile X syndrome. PLoS One. 2011;6(10):e26203.

Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131(5):861-72.

US Burden of Disease Collaborators. The state of US health, 1990-2010: burden of diseases, injuries, and risk factors. JAMA. 2013;310(6):591-608.

Yu J, Vodyanik MA, Smuga-Otto K, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318(5858):1917-20.

Mechanisms of critical-period development

Aton SJ, Broussard C, Dumoulin M, et al. Visual experience and subsequent sleep induce sequential plastic changes in putative inhibitory and excitatory cortical neurons. Proc Natl Acad Sci U S A.2013;110(8):3101-6.

Bavelier D, Levi DM, Li RW, et al. Removing brakes on adult brain plasticity: from molecular to behavioral interventions. J Neurosci. 2010;30(45):14964-71.

Bernhardt BC, Singer T. The neural basis of empathy. Annu Rev Neurosci. 2012;35:1-23.

Condé F, Lund JS, Lewis DA. The hierarchical development of monkey visual cortical regions as revealed by the maturation of parvalbumin-immunoreactive neurons. Brain Res Dev Brain Res. 1996;96(1-2):261-76.

Gervain J, Vines BW, Chen LM, et al. Valproate reopens critical-period learning of absolute pitch. Front Syst Neurosci. 2013;7:102.

Hensch TK. Bistable parvalbumin circuits pivotal for brain plasticity. Cell. 2014;156(1-2):17-9.

Hensch TK. Critical period plasticity in local cortical circuits. Nat Rev Neurosci. 2005;6(11):877-88.

Hensch TK, Bilimoria PM. Re-opening windows: manipulating critical periods for brain development. Cerebrum. 2012;2012:11.

Menon V, Uddin LQ. Saliency, switching, attention and control: a network model of insula function. Brain Struct Funct. 2010;214(5-6):655-67.

Morishita H, Hensch TK. Critical period revisited: impact on vision. Curr Opin Neurobiol. 2008;18(1):101-7.

Nieuwenhuys R. The insular cortex: a review. Prog Brain Res. 2012;195:123-63.

Spatazza J, Lee HH, Di Nardo AA, et al. A. Choroid-plexus-derived Otx2 homeoprotein constrains adult cortical plasticity. Cell Rep. 2013;3(6):1815-23.

Takesian AE, Hensch TK. Balancing plasticity/stability across brain development. Prog Brain Res. 2013;207:3-34.

Werker JF, Hensch TK. Critical periods in speech perception: new directions. Annu Rev Psychol. 2015;66:173-96.

Yazaki-Sugiyama Y, Kang S, Câteau H, et al. Bidirectional plasticity in fast-spiking GABA circuits by visual experience. Nature. 2009;462(7270):218-21.

Transcriptional landscape of the developing brain

Lui JH, Hansen DV, Kriegstein AR. Development and evolution of the human neocortex. Cell. 2011;146(1):18-36.

Miller JA, Ding SL, Sunkin SM, et al. Transcriptional landscape of the prenatal human brain. Nature. 2014;508(7495):199-206.

Sorensen SA, Bernard A, Menon V, et al. Correlated gene expression and target specificity demonstrate excitatory projection neuron diversity. Cereb Cortex. 2015;25(2):433-49.

New tools to investigate brain development

Aarnoudse-Moens CS, Oosterlaan J, Duivenvoorden HJ, et al. Development of preschool and academic skills in children born very preterm. J Pediatr. 2011;158(1):51-6.

Ball G, Boardman JP, Aljabar P, et al. The influence of preterm birth on the developing thalamocortical connectome. Cortex. 2013;49(6):1711-21.

Ball G, Boardman JP, Rueckert D, et al. The effect of preterm birth on thalamic and cortical development. Cereb Cortex. 2012;22(5):1016-24.

Delobel-Ayoub M, Arnaud C, White-Koning M, et al. Behavioral problems and cognitive performance at 5 years of age after very preterm birth: the EPIPAGE Study. Pediatrics. 2009;123(6):1485-92.

Doria V, Beckmann CF, Arichi T, et al. Emergence of resting state networks in the preterm human brain. Proc Natl Acad Sci U S A. 2010;107(46):20015-20.

McKinstry RC, Mathur A, Miller JH, et al. Radial organization of developing preterm human cerebral cortex revealed by non-invasive water diffusion anisotropy MRI. Cereb Cortex. 2002;12(12):1237-43.

Pandit AS, Robinson E, Aljabar P, et al. Whole-brain mapping of structural connectivity in infants reveals altered connection strength associated with growth and preterm birth. Cereb Cortex. 2014;24(9):2324-33.

Language learning

Akiyama LF, Richards TR, Imada T, et al. Age-specific average head template for typically developing 6-month-old infants. PLoS One. 2013;8(9):e73821.

Deniz Can D, Richards T, Kuhl PK. Early gray-matter and white-matter concentration in infancy predict later language skills: a whole brain voxel-based morphometry study. Brain Lang. 2013;124(1):34-44.

Garcia-Sierra A, Rivera-Gaxiola M, Percaccio CP, et al. Bilingual language learning: An ERP study relating early brain responses to speech, language input, and later word production. J Phon. 2011.

Kuhl PK. Early language acquisition: cracking the speech code. Nat Rev Neurosci. 2004;5(11):831-43.

Kuhl PK, Andruski JE, Chistovich IA, et al. Cross-language analysis of phonetic units in language addressed to infants. Science. 1997;277(5326):684-6.

Kuhl PK, Stevens E, Hayashi A, et al. Infants show a facilitation effect for native language phonetic perception between 6 and 12 months. Dev Sci. 2006;9(2):F13-F21.

Kuhl PK, Tsao FM, Liu HM. Foreign-language experience in infancy: effects of short-term exposure and social interaction on phonetic learning. Proc Natl Acad Sci U S A. 2003;100(15):9096-101.

Meltzoff AN, Kuhl PK, Movellan J, Sejnowski TJ. Foundations for a new science of learning. Science. 2009;325(5938):284-8.

Ramírez-Esparza N, García-Sierra A, Kuhl PK. Look who's talking: speech style and social context in language input to infants are linked to concurrent and future speech development. Dev Sci. 2014;17(6):880-91.

Rivera-Gaxiola M, Silva-Pereyra J, Kuhl PK. Brain potentials to native and non-native speech contrasts in 7- and 11-month-old American infants. Dev Sci. 2005;8(2):162-72.

Yeatman JD, Dougherty RF, Ben-Shachar M, Wandell BA. Development of white matter and reading skills. Proc Natl Acad Sci U S A. 2012;109(44):E3045-53.

Early attachment, emotional development, and adversity

Bakermans-Kranenburg MJ, van Ijzendoorn MH. Gene-environment interaction of the dopamine D4 receptor (DRD4) and observed maternal insensitivity predicting externalizing behavior in preschoolers. Dev Psychobiol. 2006;48(5):406-9.

Bakermans-Kranenburg MJ, van Ijzendoorn MH, Juffer F. Less is more: meta-analyses of sensitivity and attachment interventions in early childhood. Psychol Bull. 2003;129(2):195-215.

Berry D, Blair C, Ursache A, et al. Family Life Project Key Investigators. Early childcare, executive functioning, and the moderating role of early stress physiology. Dev Psychol. 2014;50(4):1250-61.

Boom DC van den. The influence of temperament and mothering on attachment and exploration: an experimental manipulation of sensitive responsiveness among lower-class mothers with irritable infants. Child Dev. 1994;65(5):1457-77.

Boyce WT, Ellis BJ. Biological sensitivity to context: I. An evolutionary-developmental theory of the origins and functions of stress reactivity. Dev Psychopathol. 2005;17(2):271-301.

Brody GH, Beach SR, Chen YF, et al. Perceived discrimination, serotonin transporter linked polymorphic region status, and the development of conduct problems. Dev Psychopathol. 201;23(2):617-27.

Cassidy J, Woodhouse SS, Sherman LJ, et al. Enhancing infant attachment security: an examination of treatment efficacy and differential susceptibility. Dev Psychopathol. 2011;23(1):131-48.

De Wolff MS, van Ijzendoorn MH. Sensitivity and attachment: a meta-analysis on parental antecedents of infant attachment. Child Dev. 1997;68(4):571-91.

Gatt JM, Nemeroff CB, Dobson-Stone C, et al. Interactions between BDNF Val66Met polymorphism and early life stress predict brain and arousal pathways to syndromal depression and anxiety. Mol Psychiatry. 2009;14(7):681-95.

Goldsmith HH, Alansky JA. Maternal and infant temperamental predictors of attachment: a meta-analytic review. J Consult Clin Psychol. 1987;55(6):805-16.

Groh AM, Roisman GI, van Ijzendoorn MH, et al. The significance of insecure and disorganized attachment for children's internalizing symptoms: a meta-analytic study. Child Dev. 2012;83(2):591-610.

Hankin BL, Nederhof E, Oppenheimer CW, et al. Differential susceptibility in youth: evidence that 5-HTTLPR x positive parenting is associated with positive affect 'for better and worse'. Transl Psychiatry. 2011;1:e44.

Lucassen N, Tharner A, van Ijzendoorn MH, et al. The association between paternal sensitivity and infant-father attachment security: a meta-analysis of three decades of research. J Fam Psychol. 2011;25(6):986-92.

Obradovic J, Bush NR, Boyce WT. The interactive effect of marital conflict and stress reactivity on externalizing and internalizing symptoms: the role of laboratory stressors. Dev Psychopathol. 2011;23(1):101-14.

Pitzer M, Jennen-Steinmetz C, Esser G, et al. Differential susceptibility to environmental influences: the role of early temperament and parenting in the development of externalizing problems. Compr Psychiatry. 2011;52(6):650-8.

Pluess M, Belsky J. Differential susceptibility to rearing experience: the case of childcare. J Child Psychol Psychiatry. 2009;50(4):396-404.

Infant neural mirroring and social cognition

Cvencek D, Meltzoff AN, Greenwald AG. Math-gender stereotypes in elementary school children. Child Dev. 2011;82(3):766-79.

Cvencek D, Meltzoff AN, Kapur M. Cognitive consistency and math-gender stereotypes in Singaporean children. J Exp Child Psychol. 2014;117:73-91.

Marshall PJ, Meltzoff AN. Neural mirroring mechanisms and imitation in human infants. Philos Trans R Soc Lond B Biol Sci. 2014;369(1644):20130620.

Marshall PJ, Young T, Meltzoff AN. Neural correlates of action observation and execution in 14-month-old infants: an event-related EEG desynchronization study. Dev Sci. 2011;14(3):474-80.

Meltzoff AN. Infant Imitation after a 1-week delay: long-term memory for novel acts and multiple stimuli. Dev Psychol. 1988;24(4):470-6.

Meltzoff AN. 'Like me': a foundation for social cognition. Dev Sci. 2007;10(1):126-34.

Meltzoff AN, Moore MK. Imitation of facial and manual gestures by human neonates. Science. 1977;198(4312):74-8.

Repacholi BM, Meltzoff AN. Emotional eavesdropping: infants selectively respond to indirect emotional signals. Child Dev. 2007;78(2):503-21.

Repacholi BM, Meltzoff AN, Olsen B. Infants' understanding of the link between visual perception and emotion: "If she can't see me doing it, she won't get angry." Dev Psychol. 2008;44(2):561-74.

Saby JN, Marshall PJ, Meltzoff AN. Neural correlates of being imitated: an EEG study in preverbal infants. Soc Neurosci. 2012;7(6):650-61.

Saby JN, Meltzoff AN, Marshall PJ. Infants' somatotopic neural responses to seeing human actions: I've got you under my skin. PLoS One. 2013;8(10):e77905.

Maternal stress and neurodevelopment: placental mechanisms in mice

Howerton CL, Bale TL. Targeted placental deletion of OGT recapitulates the prenatal stress phenotype including hypothalamic mitochondrial dysfunction. Proc Natl Acad Sci U S A. 2014;111(26):9639-44.

Howerton CL, Morgan CP, Fischer DB, Bale TL. O-GlcNAc transferase (OGT) as a placental biomarker of maternal stress and reprogramming of CNS gene transcription in development. Proc Natl Acad Sci U S A. 2013;110(13):5169-74.

Morgan CP, Bale TL. Early prenatal stress epigenetically programs dysmasculinization in second-generation offspring via the paternal lineage. J Neurosci. 2011;31(33):11748-55.

Mueller BR, Bale TL. Sex-specific programming of offspring emotionality after stress early in pregnancy. J Neurosci. 2008;28(36):9055-65.

Rossant J, Cross JC. Placental development: lessons from mouse mutants. Nat Rev Genet. 2001;2(7):538-48.

Early experience and neuro-affective development

Baker KD, Den ML, Graham BM, Richardson R. A window of vulnerability: impaired fear extinction in adolescence. Neurobiol Learn Mem. 2014;113:90-100.

Blasi A, Mercure E, Lloyd-Fox S, et al. Early specialization for voice and emotion processing in the infant brain. Curr Biol. 2011;21(14):1220-4.

Bouwmeester H, Wolterink G, van Ree JM. Neonatal development of projections from the basolateral amygdala to prefrontal, striatal, and thalamic structures in the rat. J Comp Neurol. 2002;442(3):239-49.

Bouwmeester H, Smits K, Van Ree JM. Neonatal development of projections to the basolateral amygdala from prefrontal and thalamic structures in rat. J Comp Neurol. 2002;450(3):241-55.

Cressman VL, Balaban J, Steinfeld S, et al. Prefrontal cortical inputs to the basal amygdala undergo pruning during late adolescence in the rat. J Comp Neurol. 2010;518(14):2693-709.

Dehaene-Lambertz G, Montavont A, Jobert A, et al. Language or music, mother or Mozart? Structural and environmental influences on infants' language networks. Brain Lang. 2010;114(2):53-65.

Gabard-Durnam LJ, Flannery J, Goff B, et al. The development of human amygdala functional connectivity at rest from 4 to 23 years: a cross-sectional study. Neuroimage. 2014;95:193-207.

Gee DG, Gabard-Durnam LJ, Flannery J, et al. Early developmental emergence of human amygdala-prefrontal connectivity after maternal deprivation. Proc Natl Acad Sci U S A. 2013;110(39):15638-43.

Gee DG, Humphreys KL, Flannery J, et al. A developmental shift from positive to negative connectivity in human amygdala-prefrontal circuitry. J Neurosci. 2013;33(10):4584-93.

Pattwell SS, Bath KG, Casey BJ, et al. Selective early-acquired fear memories undergo temporary suppression during adolescence. Proc Natl Acad Sci U S A. 2011;108(3):1182-7.

Vyas A, Mitra R, Shankaranarayana Rao BS, Chattarji S. Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neurons. J Neurosci. 2002;22(15):6810-8.

Impact of poverty on the developing brain

Hackman DA, Farah MJ. Socioeconomic status and the developing brain. Trends Cogn Sci. 2009;13(2):65-73.

Hackman DA, Farah MJ, Meaney MJ. Socioeconomic status and the brain: mechanistic insights from human and animal research. Nat Rev Neurosci. 2010;11(9):651-9.

Lawson GM, Duda JT, Avants BB, et al. Associations between children's socioeconomic status and prefrontal cortical thickness. Dev Sci. 2013;16(5):641-52.

Noble KG, Houston SM, Kan E, Sowell ER. Neural correlates of socioeconomic status in the developing human brain. Dev Sci. 2012;15(4):516-27.

Raizada RD, Richards TL, Meltzoff A, Kuhl PK. Socioeconomic status predicts hemispheric specialisation of the left inferior frontal gyrus in young children. Neuroimage. 2008;40(3):1392-401.

Rao H, Betancourt L, Giannetta JM, et al. Early parental care is important for hippocampal maturation: evidence from brain morphology in humans. Neuroimage. 2010;49(1):1144-50.

Sheridan MA, How J, Araujo M, et al. What are the links between maternal social status, hippocampal function, and HPA axis function in children? Dev Sci. 2013;16(5):665-75.

Sheridan MA, Sarsour K, Jutte D, et al. The impact of social disparity on prefrontal function in childhood. PLoS One. 2012;7(4):e35744.

Stevens C, Lauinger B, Neville H. Differences in the neural mechanisms of selective attention in children from different socioeconomic backgrounds: an event-related brain potential study. Dev Sci. 2009;12(4):634-46.

Windows of opportunity and vulnerability

Almas AN, Degnan KA, Radulescu A, et al. Effects of early intervention and the moderating effects of brain activity on institutionalized children's social skills at age 8. Proc Natl Acad Sci U S A. 2012;109 Suppl 2:17228-31.

Johnson DE, Guthrie D, Smyke AT, et al. Growth and associations between auxology, caregiving environment, and cognition in socially deprived Romanian children randomized to foster vs ongoing institutional care. Arch Pediatr Adolesc Med. 2010;164(6):507-16.

Marshall PJ, Reeb BC, Fox NA, et al. Effects of early intervention on EEG power and coherence in previously institutionalized children in Romania. Dev Psychopathol. 2008;20(3):861-80.

McLaughlin KA, Fox NA, Zeanah CH, et al. Delayed maturation in brain electrical activity partially explains the association between early environmental deprivation and symptoms of attention-deficit/hyperactivity disorder. Biol Psychiatry. 2010;68(4):329-36.

McLaughlin KA, Fox NA, Zeanah CH, Nelson CA. Adverse rearing environments and neural development in children: the development of frontal electroencephalogram asymmetry. Biol Psychiatry. 2011;70(11):1008-15.

McLaughlin KA, Sheridan MA, Winter W, et al. Widespread reductions in cortical thickness following severe early-life deprivation: a neurodevelopmental pathway to attention-deficit/hyperactivity disorder. Biol Psychiatry. 2014;76(8):629-38.

Nelson CA 3rd, Zeanah CH, Fox NA, et al. Cognitive recovery in socially deprived young children: the Bucharest Early Intervention Project. Science. 2007;318(5858):1937-40.

Smyke AT, Zeanah CH Jr, Fox NA, Nelson CA 3rd. A new model of foster care for young children: the Bucharest early intervention project. Child Adolesc Psychiatr Clin N Am. 2009;18(3):721-34.

Smyke AT, Zeanah CH, Gleason MM, et al. A randomized controlled trial comparing foster care and institutional care for children with signs of reactive attachment disorder. Am J Psychiatry. 2012;169(5):508-14.

Vanderwert RE, Marshall PJ, Nelson CA 3rd, et al. Timing of intervention affects brain electrical activity in children exposed to severe psychosocial neglect. PLoS One. 2010;5(7):e11415.

Zeanah CH, Nelson CA, Fox NA, et al. Designing research to study the effects of institutionalization on brain and behavioral development: the Bucharest Early Intervention Project. Dev Psychopathol. 2003;15(4):885-907.

Standardizing growth and nutritional status biomarkers

Bhutta ZA, Das JK, Rizvi A, et al. Lancet Nutrition Interventions Review Group; Maternal and Child Nutrition Study Group. Evidence-based interventions for improvement of maternal and child nutrition: what can be done and at what cost? Lancet. 2013;382(9890):452-77.

Frongillo EA, Tofail F, Hamadani JD, et al. Measures and indicators for assessing impact of interventions integrating nutrition, health, and early childhood development. Ann N Y Acad Sci. 2014;1308:68-88.

Frongillo EA Jr. Validation of measures of food insecurity and hunger. J Nutr. 1999;129(2S Suppl):506S-509S.

Lampl M, Johnson ML. Infant growth in length follows prolonged sleep and increased naps. Sleep. 2011;34(5):641-50.

Lampl M, Johnson ML, Frongillo EA Jr. Mixed distribution analysis identifies saltation and stasis growth. Ann Hum Biol. 2001;28(4):403-11.

Leroy JL, Ruel M, Habicht JP, Frongillo EA. Linear growth deficit continues to accumulate beyond the first 1000 days in low- and middle-income countries: global evidence from 51 national surveys. J Nutr. 2014;144(9):1460-6.

Onis M de, Garza C, Habicht JP. Time for a new growth reference. Pediatrics. 1997;100(8):E8.

Onis M de, Onyango A, Borghi E, et al. WHO Multicentre Growth Reference Study Group. Worldwide implementation of the WHO Child Growth Standards. Public Health Nutr. 2012;15(9):1603-10.

The most useful biomarkers for optimal childhood development

Aboud FE, Yousafzai AK. Global health and development in early childhood. Annu Rev Psychol. 2015;66:433-57.

Best C, Neufingerl N, Del Rosso JM, et al. Can multi-micronutrient food fortification improve the micronutrient status, growth, health, and cognition of schoolchildren? A systematic review. Nutr Rev. 2011;69(4):186-204.

Campbell F, Conti G, Heckman JJ, et al. Early childhood investments substantially boost adult health. Science. 2014;343(6178):1478-85.

Cooper WN, Khulan B, Owens S, et al. DNA methylation profiling at imprinted loci after periconceptional micronutrient supplementation in humans: results of a pilot randomized controlled trial. FASEB J. 2012;26(5):1782-90.

Eilander A, Gera T, Sachdev HS, et al. Multiple micronutrient supplementation for improving cognitive performance in children: systematic review of randomized controlled trials. Am J Clin Nutr. 2010;91(1):115-30.

Gertler P, Heckman J, Pinto R, et al. Labor market returns to an early childhood stimulation intervention in Jamaica. Science. 2014;344(6187):998-1001.

Levitsky DA, Barnes RH. Nutritional and environmental interactions in the behavioral development of the rat: long-term effects. Science. 1972;176(4030):68-71.

Prado EL, Dewey KG. Nutrition and brain development in early life. Nutr Rev. 2014;72(4):267-84.

Ramakrishnan U, Goldenberg T, Allen LH. Do multiple micronutrient interventions improve child health, growth, and development? J Nutr. 2011;141(11):2066-75.

Sachdev H, Gera T, Nestel P. Effect of iron supplementation on mental and motor development in children: systematic review of randomised controlled trials. Public Health Nutr. 2005;8(2):117-32.

Victora CG, de Onis M, Hallal PC, et al. Worldwide timing of growth faltering: revisiting implications for interventions. Pediatrics. 2010;125(3):e473-80.

Timing interventions to optimize brain development

Christian P, Murray-Kolb LE, Khatry SK, et al. Prenatal micronutrient supplementation and intellectual and motor function in early school-aged children in Nepal. JAMA. 2010;304(24):2716-23.

Fretham SJ, Carlson ES, Wobken J, et al. Temporal manipulation of transferrin-receptor-1-dependent iron uptake identifies a sensitive period in mouse hippocampal neurodevelopment. Hippocampus. 2012;22(8):1691-702.

Insel BJ, Schaefer CA, McKeague IW, et al. Maternal iron deficiency and the risk of schizophrenia in offspring. Arch Gen Psychiatry. 2008;65(10):1136-44.

Kennedy BC, Dimova JG, Siddappa AJ, et al. Prenatal choline supplementation ameliorates the long-term neurobehavioral effects of fetal-neonatal iron deficiency in rats. J Nutr. 2014;144(11):1858-65.

Kretchmer N, Beard JL, Carlson S. The role of nutrition in the development of normal cognition. Am J Clin Nutr. 1996;63(6):997S-1001S.

Lozoff B, Jimenez E, Hagen J, et al. Poorer behavioral and developmental outcome more than 10 years after treatment for iron deficiency in infancy. Pediatrics. 2000;105(4):E51.

Lukowski AF, Koss M, Burden MJ, et al. Iron deficiency in infancy and neurocognitive functioning at 19 years: evidence of long-term deficits in executive function and recognition memory. Nutr Neurosci. 2010;13(2):54-70.

Pongcharoen T, Ramakrishnan U, DiGirolamo AM, et al. Influence of prenatal and postnatal growth on intellectual functioning in school-aged children. Arch Pediatr Adolesc Med. 2012;166(5):411-6.

Riggins T, Miller NC, Bauer PJ, et al. Consequences of low neonatal iron status due to maternal diabetes mellitus on explicit memory performance in childhood. Dev Neuropsychol. 2009;34(6):762-79.

Schmidt RJ, Tancredi DJ, Krakowiak P, et al. Maternal intake of supplemental iron and risk of autism spectrum disorder. Am J Epidemiol. 2014;180(9):890-900.

Thompson RA, Nelson CA. Developmental science and the media. Early brain development. Am Psychol. 2001;56(1):5-15.

Tran PV, Carlson ES, Fretham SJ, Georgieff MK. Early-life iron deficiency anemia alters neurotrophic factor expression and hippocampal neuron differentiation in male rats. J Nutr. 2008;138(12):2495-501.

Tran PV, Fretham SJ, Carlson ES, Georgieff MK. Long-term reduction of hippocampal brain-derived neurotrophic factor activity after fetal-neonatal iron deficiency in adult rats. Pediatr Res. 2009;65(5):493-8.

Wachs TD, Georgieff M, Cusick S, McEwen BS. Issues in the timing of integrated early interventions: contributions from nutrition, neuroscience, and psychological research. Ann N Y Acad Sci. 2014;1308:89-106.

A paradigm for interdisciplinary approaches to nutritional neuroscience

Lozoff B. Early iron deficiency has brain and behavior effects consistent with dopaminergic dysfunction. J Nutr. 2011;141(4):740S-746S.

Lozoff B. Iron deficiency and child development. Food Nutr Bull. 2007;28(4 Suppl):S560-71.

Lozoff B. Perinatal iron deficiency and the developing brain. Pediatr Res. 2000;48(2):137-9.

Lozoff B, Beard J, Connor J, et al. Long-lasting neural and behavioral effects of iron deficiency in infancy. Nutr Rev. 2006;64(5 Pt 2):S34-43; discussion S72-91.

Lozoff B, Georgieff MK. Iron deficiency and brain development. Semin Pediatr Neurol. 2006;13(3):158-65.

Walker SP, Wachs TD, Gardner JM, et al. International Child Development Steering Group. Child development: risk factors for adverse outcomes in developing countries. Lancet. 2007;369(9556):145-57.

Cortical maturation and white matter myelination in early childhood

Lamar M, Zhou XJ, Charlton RA, et al. In vivo quantification of white matter microstructure for use in aging: a focus on two emerging techniques. Am J Geriatr Psychiatry. 2014;22(2):111-21.

Spader HS, Ellermeier A, O'Muircheartaigh J, et al. Advances in myelin imaging with potential clinical application to pediatric imaging. Neurosurg Focus. 2013;34(4):E9.

Western diets, postpartum depression, and developmental programming

Bilbo SD, Tsang V. Enduring consequences of maternal obesity for brain inflammation and behavior of offspring. FASEB J. 2010;24(6):2104-15.

Bolton JL, Bilbo SD. Developmental programming of brain and behavior by perinatal diet: focus on inflammatory mechanisms. Dialogues Clin Neurosci. 2014;16(3):307-20.

Responsive caregiving and executive function

Landry SH, Smith KE, Swank PR, Guttentag C. A responsive parenting intervention: the optimal timing across early childhood for impacting maternal behaviors and child outcomes. Dev Psychol. 2008;44(5):1335-53.

Tools for studying nutritional enhancement of learning and memory

Baym CL, Khan NA, Monti JM, et al. Dietary lipids are differentially associated with hippocampal-dependent relational memory in prepubescent children. Am J Clin Nutr. 2014;99(5):1026-32.

Baym CL, Khan NA, Pence A, et al. Aerobic fitness predicts relational memory but not item memory performance in healthy young adults. J Cogn Neurosci. 2014;26(11):2645-52.

Chaddock L, Erickson KI, Prakash RS, et al. A neuroimaging investigation of the association between aerobic fitness, hippocampal volume, and memory performance in preadolescent children. Brain Res. 2010;1358:172-83.

Erickson KI, Voss MW, Prakash RS, et al. Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci U S A. 2011;108(7):3017-22.

Hannula DE, Ryan JD, Tranel D, Cohen NJ. Rapid onset relational memory effects are evident in eye movement behavior, but not in hippocampal amnesia. J Cogn Neurosci. 2007;19(10):1690-705.

Konkel A, Warren DE, Duff MC, et al. Hippocampal amnesia impairs all manner of relational memory. Front Hum Neurosci. 2008;2:15.

Maguire EA, Woollett K, Spiers HJ. London taxi drivers and bus drivers: a structural MRI and neuropsychological analysis. Hippocampus. 2006;16(12):1091-101.

Monti JM, Hillman CH, Cohen NJ. Aerobic fitness enhances relational memory in preadolescent children: the FITKids randomized control trial. Hippocampus. 2012;22(9):1876-82.

Snyder JS, Soumier A, Brewer M, et al. Adult hippocampal neurogenesis buffers stress responses and depressive behaviour. Nature. 2011;476(7361):458-61.

Stangl D, Thuret S. Impact of diet on adult hippocampal neurogenesis. Genes Nutr. 2009;4(4):271-82.

Watson PD, Voss JL, Warren DE, et al. Spatial reconstruction by patients with hippocampal damage is dominated by relational memory errors. Hippocampus. 2013;23(7):570-80.

Translating the neuroscience of parenting into interventions for parents: Minding the Baby

Fonagy P, Gergely G, Target M. The parent-infant dyad and the construction of the subjective self. J Child Psychol Psychiatry. 2007;48(3-4):288-328.

House JS, Landis KR, Umberson D. Social relationships and health. Science. 1988;241(4865):540-5.

Ordway MR, Sadler LS, Dixon J, et al. Lasting effects of an interdisciplinary home visiting program on child behavior: preliminary follow-up results of a randomized trial. J Pediatr Nurs. 2014;29(1):3-13.

Sadler LS, Slade A, Close N, et al. Minding the Baby: Enhancing reflectiveness to improve early health and relationship outcomes in an interdisciplinary home visiting program. Infant Ment Health J. 2013;34(5):391-405.

Swain JE, Lorberbaum JP, Kose S, Strathearn L. Brain basis of early parent-infant interactions: psychology, physiology, and in vivo functional neuroimaging studies. J Child Psychol Psychiatry. 2007;48(3-4):262-87.

Intervention to help close the word gap

Fernald A, Marchman VA, Weisleder A. SES differences in language processing skill and vocabulary are evident at 18 months. Dev Sci. 2013;16(2):234-48.

Hart B, Risley TR. The early catastrophe: the 30 million word gap by age 3. American Educator. 2003.

Murphey D, Cooper M, Forry N. The youngest Americans: a statistical portrait of infants and toddlers in the United States. 2013.

Building early childhood systems: advancing quality, equity, and sustainability

Campbell FA, Pungello EP, Burchinal M, et al. Adult outcomes as a function of an early childhood educational program: an Abecedarian Project follow-up. Dev Psychol. 2012;48(4):1033-43.

Kagan SL. Neuman M J. Three decades of transition research: What does it tell us? Elementary School Journal. 1998; 98:365-80.

Reynolds AJ, Temple JA, White BA, et al. Age 26 cost-benefit analysis of the child-parent center early education program. Child Dev. 2011;82(1):379-404.

Votruba-Drzal E, Coley RL, Chase-Lansdale PL. Child care and low-income children's development: direct and moderated effects. Child Dev. 2004;75(1):296-312.

Websites

Thirty Million Words Initiative
A program developed at the University of Chicago that aims to build language-based interactions between parents and young children.

American Academy of Pediatrics. International and U.S. Growth Charts.

Centers for Disease Control and Prevention. Behavioral Risk Factor Surveillance System.
A database of information from an ongoing national survey on adult behavioral health factors.

KIDS COUNT — The Annie E. Casey Foundation. Data Center.
A foundation-funded project providing data and trend analysis about the well-being of children in the United States.

TED. Patricia Kuhl: The Linguistic Genius of Babies. 2010.

Too Small to Fail
An initiative that promotes research on early child development and aims to help parents, businesses and communities identify actions that improve the health and well-being of children up to 5 years old.

UNICEF Data: Monitoring the Situation of Children and Women
Surveys and statistics on child and maternal health around the world.

Yale School of Medicine. Yale Child Study Center. Minding the Baby.
An intensive intervention for first-time young mothers and their families.

Zero to Three
A national nonprofit organization that provides parents and policy makers with information about early development.

Books and Reports

Black MM, Dewey KG, eds. Every Child's Potential: Integrating Nutrition and Early Childhood Development Interventions. Annals of the New York Academy of Sciences. 2014;1308:1-225.

Burgess K, Chien N, Morissey T, Swenson K. Trends in the Use of Early Care and Education, 1995-2011: Descriptive Analysis of Child Care Arrangements from National Survey Data. ASPE Research Brief. U.S. Department of Health and Human Services. 2014.

Committee on a Framework for Development a New Taxonomy of Disease; National Research Council. Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease. Washington, DC: National Academies Press; 2011.

Hart B, Risley TR. Meaningful Differences in the Everyday Experiences of Young Children. Baltimore, MD: Paul H. Brookes Publishing Co.; 1995.

Lee VE, Burkam DT. Inequality at the starting gate: Social background differences in achievement as children begin school. Economic Policy Institute. 2002.

National Institutes of Health. BRAIN 2025: A Scientific Vision. Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Working Group Report to the Advisory Committee to the Director, NIH. 2014.

Shonkoff JP, Phillips DA, eds. From Neurons to Neighborhoods: The Science of Early Childhood Development. Washington, DC: National Academy Press; 2000.

UNICEF. Building Better Brains: New Frontiers in Early Childhood Development. 2014.

Whitebook M, Barnett WS. Degrees in context: Asking the right questions about preparing skilled and effective teachers of young children. National Institute for Early Education Research. 2011.

World Health Organization. Physical Status: The Use and Interpretation of Anthropometry. 1995.

World Health Organization. WHO Multicentre Growth Reference Study Group. WHO Child Growth Standards: Length/height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age: Methods and development. Geneva, Switzerland. 2006.

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Highlights

Programs that teach parents how to verbally engage with children from a very young age can help socioeconomically disadvantaged children stay developmentally on track.

With tools that probe brain development—from genes to behavior to social interactions—researchers can better understand neurodevelopmental disorders as well as the educational needs of young children.

Introduction

The first 1000 days of a child's life—from conception to age 2—are packed with foundational developmental milestones. The brain is vigorously forming new connections based on inputs from the outside world. Healthy brain development during this period provides a solid foundation for physical, emotional, and intellectual well-being throughout life.

Early life is a very active time in brain development. Nutritional or other deficiencies can derail key developmental trajectories. (Image courtesy of Michael K. Georgieff)

However, millions of children around the world experience environmental stressors such as poverty, inadequate nutrition, poor child care, and parental neglect that have been negatively correlated with different aspects of brain development. Thus, while early life is a window of opportunity for shaping brain function, it is also a period of vulnerability. Over the past two decades, research has highlighted the connection between brain development and early social, emotional, and cognitive milestones, as well as how external influences shape both.

The conference began with a public lecture on the so-called word gap between socioeconomically disadvantaged and socioeconomically advantaged children. Panelists talked about how babies learn language through social interaction, presenting new imaging techniques that enhance our understanding of language learning and describing interventions to teach parents how to interact with young children. Over the next two days, speakers covered topics in the biology of early brain development, looking at the neurological effects of environmental adversity and how to intervene to protect at-risk children.

Baby talk: closing the achievement gap, word by word

Former Secretary of State Hillary Rodham Clinton opened the conference with special introductory remarks via video address. She introduced the topic of the public lecture: the word gap. Daily interactions between caregivers and children, such as talking, reading, and singing, "lay a foundation for future success long before a child steps foot into a classroom for the first time" she said. "Sadly, however, many of our kids are not getting the support they need to grow and thrive to their fullest potential." Research shows that by 4 years old, children from low socioeconomic backgrounds tend to hear 30 million fewer words than their peers, setting them at a disadvantage from the beginning of school. The Clinton Foundation launched its Too Small to Fail initiative to put children on the path to success.

Michael H. Levine of the Joan Ganz Cooney Center at Sesame Workshop moderated the public lecture on disparities in early learning. Humans learn more during their first 5 years than during any other period, explained Patricia K. Kuhl of the University of Washington; language development is a central piece of this early period of brain plasticity. Language learning is a social process that can only take place with verbal stimulation from adults. Kuhl has found that hearing a type of speech termed parentese—the high-pitched, slow speech often used to speak to young children—improves infant language development dramatically.

Dana Suskind of the University of Chicago Medicine talked about her work with the Thirty Million Words Initiative, which aims to translate research into evidence-based interventions that teach parents to use language to promote their child's cognitive development. Programs use biweekly recordings of parent–child interactions to track how well parents implement "the 3 T's"—tuning in, talking more, and taking turns—when communicating with their children, as well as to track the child’s language development. Patti Miller from Too Small to Fail described a tool kit that gives parents prompts for engaging young children. She also mentioned the organization's work with Hollywood and Spanish-language media to promote the importance of talking, reading, and singing to children from infancy, encouraging companies to model such behavior on television and in other media.

It is challenging to educate parents about the importance of early language development. Implementation of interventions requires not just buy-in from parents but also support and investment on a national scale. Miller advocated using technology to disseminate tools and guidance to parents and pediatricians. Kuhl stressed the need for basic research to understand the neurological mechanisms by which such interventions work. Suskind noted that pressures on socioeconomically disadvantaged families can make it difficult to prioritize child interactions but pointed to the importance of educating parents, who need to understand how powerful early interactions are in children's development.

Keynote address: how will we map neurodevelopment?

Researchers know remarkably little about how the brain works, compared to other organ systems. Keynote speaker Thomas R. Insel, director of the National Institute of Mental Health, pointed to the urgent need to close this gap given the global burden of neurodevelopmental disorders. Modern tools make it possible to map the brain on multiple levels, "from sequence to society."

The keynote address looked at how brain-mapping technology has informed our understanding of neurodevelopment. Techniques that map gene expression across time reveal stark differences between the developing brain and the adult brain. Induced pluripotent stem cell technology allows researchers to create patient-specific neurons to study disease processes in human cells. Tiny microscopes placed into the mouse brain provide a peak at the still-encrypted, complex neural code, while neural imaging reveals the development of connectivity in the human brain to an unprecedented level of detail. The BRAIN Initiative, launched in 2013, promises to yield new methods to understand how we think, learn, and remember.

To understand behavior, researchers are embracing noninvasive tracking of phenotypic data, such as physical activity, sleep, and EEG measurements, on a large scale. An effort to create a cognitive growth chart is revealing a different rate of development for each cognitive function. Researchers are even decoding social networks to understand our behavior. The unifying theme of recent findings is the dialogue between biological and behavioral development. Research is unraveling how social experience, stress, education, nutrition, and other factors interact with genetics to shape who we are.

Mapping the brain at multiple levels reveals how biological and behavioral development affect each other. (Image courtesy of Thomas R. Insel)

Highlights

Critical periods of brain development could be induced in later life for therapeutic purposes, but the strategy may have unintended consequence.

Open-source atlases mapping gene expression during development reveal differences among mice, primates, and humans.

Brain imaging of preterm infants suggests that prematurity causes diffuse brain injury that contributes to impaired cognitive performance.

Language studies show that babies need social interaction to learn.

A subset of children may be especially sensitive to early adversity and to interventions counteracting it.

Imitation is a powerful learning tool for babies and contributes to the adoption of stereotypes by school-aged children.

Mechanisms of critical-period brain development

Early-life experience shapes brain function during critical periods of development (also known as sensitive periods) when particular brain regions are especially responsive to inputs. Takao K. Hensch of Harvard University explained his research into how these periods get started and end. His team showed that the timing of developmental windows is dictated by a small population of inhibitory interneurons called basket cells. When the researchers blocked the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in young mice, the plasticity normally present in the visual cortex at this age was eliminated. Conversely, increasing GABA neurotransmission delayed this critical period of plasticity in the visual cortex.

"Brainbow" neuroimaging technology allows researchers to visualize individual basket cells by making each one fluoresce in a different color in the brain of a living mouse. (Image courtesy of Takao K. Hensch)

After neurodevelopment, basket cells are wrapped in extracellular matrix structures called perineuronal nets. When injected into the brain, an enzyme that dissolves these nets makes the brain plastic again. The ability to reopen critical periods points to therapeutic possibilities for treating brain injury and developmental disorders.

Recent work shows that, even in adult animals, inhibitory basket cells exist in two states—one more permissive for plasticity and one less. Neuromodulatory molecules can push the cells into the permissive state by increasing the transmission of another neurotransmitter, acetylcholine.

Enhancing acetylcholine may offer a way to reopen critical periods for therapeutic purposes—an exciting prospect because drugs that do so are already approved. The strategy is being tested in a clinical trial to restore vision. Hensch cautioned, however, that while it may be possible to rekindle critical-period-type learning in adults, the exuberant growth of neural connections during such development may cause problems in adult brains, where it is not intended to occur.

Transcriptional landscape of the developing brain

Gene sequencing can identify genes involved in neurodevelopment but cannot reveal gene function. Ed S. Lein from the Allen Institute for Brain Science is building open-source transcriptional atlases that map mammalian gene expression across different brain areas and across development. His team is standardizing, automating, and scaling-up lab techniques for measuring gene expression to create the atlases.

The group has processed more than a million samples of mouse brain tissue to map 20 000 genes. Although brain size makes sampling a challenge in primates and humans, the researchers are also working on atlases in these species. The maps show huge differences in gene expression in mice and humans, pointing to cross-species differences in function and highlighting the need for human data.

Gene expression patterns in different cortical layers and at different times in development provide snapshots of the cell types present and their states of maturation. Such maps allow researchers to link gene expression to cellular architecture and known cell processes. They also spotlight the dynamics of development—where gene expression is changing the most—which offers clues to how and when the stable, mature phenotype arises.

New tools to investigate brain development

The incidence of motor deficits in children born preterm is declining, but researchers are not good at predicting cognitive and neuropsychiatric outcomes of preterm birth. Brain imaging of preterm infants suggests they experience a kind of diffuse brain injury that contributes to a reduction in cognitive performance. Serena J. Counsell of King's College London, whose lab is part of a consortium called the Human Connectome Project, is using advanced neuroimaging techniques to study this effect.

Diffusion tensor imaging reveals that babies' brains show an increase in white matter signal from 25 weeks of gestation to 2 years old, when the pattern is close to that seen in adulthood. (Image courtesy of Serena J. Counsell)

Structural magnetic resonance imaging (sMRI) of around 100 preterm infants showed that immaturity at birth affects the growth of brain regions associated with memory and learning, including the medial temporal lobe, hippocampus, and insula. However, resting-state functional MRI (fMRI) imaging suggests that by the expected date of delivery some aspects of neuronal activity are normal in these infants.

Most of Counsell's work uses diffusion tensor imaging (DTI), which tracks the molecular motion of water in tissue using a measure called anisotropy. Researchers can use this measure to quantify brain development noninvasively in the living human brain. Anisotropy is high at 24 weeks of gestation but falls by 40 weeks, when the brain's increasing microstructure decreases the diffusivity of water. In preterm infants, however, the development of cortical microstructure is strongly delayed. Her group found that connectivity between the thalamus and the frontal cortex is also reduced, correlating with reductions in cognitive performance. Among infants in the study, 40% of the variance in cognition at 2 years old could be explained by the combined effects of these brain markers and parental socioeconomic factors, which alone accounted for 17% of the variance.

Language learning

Language learning provides a helpful window into brain development. Patricia K. Kuhl from the University of Washington uses techniques such as magnetoencephalography (MEG) and DTI to study brain and language development. Her work has elucidated the importance of social learning in brain development.

In their first 6 months, babies can discriminate sounds from all languages, but between 6 and 12 months old their perception becomes focused on the sounds relevant in their own language. Such learning is malleable: in twelve play sessions with a Japanese-speaking experimenter, American-raised 10-month-olds acquired the Japanese language soundscape. However, the same input administered through an audio recording or a DVD engendered no learning, suggesting that babies need social interaction to learn.

More recently, her group has correlated these behavioral effects with brain imaging studies. Using an MEG machine designed for infants, the researchers found elevated brain activation in the auditory and motor cortexes when babies heard spoken language, suggesting that motor areas rehearse speech based on what babies hear before they can speak. Grey and white matter development at 7 months old, particularly in the hippocampus and cerebellum, predict later language development. A bilingual environment also extends the critical period for language and promotes cognitive flexibility.

Early attachment, emotional development, and adversity

Secure attachment early in life is thought to have long-term developmental benefits, and some researchers have attributed children's attachment to the quality of early parental or caregiver care. Paradoxically, however, interventions to improve attachment generally show modest effects.

Jay Belsky of the University of California, Davis, proposed that such interventions are most effective for children with sensitive temperaments, who are more susceptible to adversity as well as to efforts to ameliorate it. Children whose temperaments are less sensitive are more resilient and less responsive to positive interventions.

Recent research from Belsky's group and others supports this idea: children who are difficult as babies are affected more by less-responsive mothers, show higher stress response to marital conflict, and have the poorest outcomes in bad day care facilities but flourish in supportive ones. Interventions are also more effective for children with certain gene variants, suggesting that those variants produce plasticity in both directions.

These data raise a question: Should interventions for children who grow up in high-risk environments be targeted more narrowly to those most likely to benefit? Further research over the next decade could help scientists identify those subgroups.

Infant neural mirroring and social cognition

Imitation plays a powerful role in learning, as Andrew N. Meltzoff of the University of Washington explained. Well before they learn to talk, babies model their actions on other people, using proprioceptive information about their own movements to understand the movements of others.

Such imitation is reflected in brain activity measured via electroencephalography (EEG). At 14 months old, babies respond similarly whether observing someone perform an action or performing it themselves. When adults mimic babies' actions, babies' brain responses are strengthened, pointing to the social importance of imitation.

The emotional content of an exchange modulates whether and how babies imitate. Normally, babies happily mimic an experimenter's action, but if a second experimenter in the room expresses anger toward the first, babies hold back. When the second experimenter leaves the room or turns away, babies imitate once again, suggesting that children track emotional history and integrate it into behavior from a very young age.

Imitation is also a powerful means by which school-aged children adopt stereotypes. In seeking to achieve a so-called cognitive balance between their self-perceptions and observations of how others treat people like them, children's identities can be overwhelmed by cultural expectations. Understanding how the brain assembles self-perception from a very young age may help researchers identify ways to diminish such stereotyping.

Highlights

In mice, maternal stress in early pregnancy dysregulates the ability of male offspring to control stress.

In both animal models and humans, parental presence influences the development of fear learning in the amygdala.

Poverty negatively affects brain development, but the mechanisms mediating this effect are unknown.

Severe neglect in childhood has strong effects on brain function, but in certain sensitive periods partial recovery may be achievable.

Maternal stress and neurodevelopment: placental mechanisms in mice

Tracy L. Bale of the University of Pennsylvania described the effects of stress in early pregnancy on fetal brain development. In mouse studies, male embryos exposed to high maternal stress became hyperresponsive to stress as adults and passed the effect onto their own offspring. These animals experienced epigenetic changes, cognitive deficits, and reduced growth.

Because only male offspring were affected, the researchers used microarray technology to identify male-specific gene expression in the placenta during early pregnancy. Placental O-glycosyltransferase (OGT), which regulates chromatin structure and other aspects of gene expression, is expressed at half the female level in males. Stress in early pregnancy further reduces placental OGT expression, perhaps pushing male levels below a protective threshold. Placental OGT is expressed similarly in humans.

Female embryonic mice express more placental OGT than male embryonic mice. When mothers experience early-pregnancy stress (EPS), placental OGT expression is reduced in both sexes. In males, it may fall below a threshold of vulnerability, leading to epigenetic changes that make the animals hyperresponsive to stress. (Image courtesy of Tracy L. Bale)

To examine the role of placental OGT in brain development, the researchers selectively silenced its expression in a transgenic mouse model. Male offspring were hyperresponsive to stress and showed diminished growth in adulthood, pointing to the gene's involvement in hypothalamic regulation. The findings demonstrate how in utero environment can have lifelong effects on stress responsiveness.

Early experience and neuro-affective development

The amygdala is important in learning emotional associations in the environment and mediates fear learning. Nim Tottenham from Columbia University showed that the development of this circuit in children is strongly shaped by parental presence.

Past work has shown that mothers have a gating effect on amygdala reactivity in very young rats. In the mother's presence pups do not exhibit fear learning, but in her absence pups show more adult-like aversive behaviors. Human children behave similarly, Tottenham's group found. In her studies, children aged 3–5 years old who did an aversive conditioning task while sitting next to a female experimenter avoided the aversive stimulus afterwards, suggesting amygdala involvement in learning. But like the rat pups, when doing the task while sitting next to their mothers children often chose the aversive stimulus later.

In another set of experiments, adopted children who had been institutionalized as infants showed higher amygdala reactivity than children who had never been institutionalized. They also showed an atypically mature pattern of connectivity between the amygdala and the prefrontal cortex, which regulates amygdala arousal in adults. These findings suggest that parental presence may extend the critical period for amygdala-related learning and that parental deprivation causes hyperactivity and atypical wiring in this circuit.

Impact of poverty on the developing brain

Poverty negatively affects brain development through a combination of outcomes associated with low socioeconomic status, including poor nutrition, low levels of education, low prestige, and poor health outcomes like premature delivery.

Martha J. Farah of the University of Pennsylvania discussed the neural correlates of poverty. Research demonstrates that socioeconomically disadvantaged children have lower levels of brain activation in the hippocampus and in a cortical area associated with language, lower performance on executive function and memory tests, and reduced ability to filter out irrelevant auditory information. These deficits implicate brain areas such as the prefrontal cortex and hippocampus. Some structural differences, for example in the hippocampus, have also been identified.

Causal pathways for these deficits are still poorly understood but may include poor nutrition and stress. In animal models, parental nurturing buffers young animals' brains from the effects of stress.

Windows of opportunity and vulnerability

Brain development depends on particular types of experiences occurring during specific windows of development; the absence of such experiences during a sensitive period can derail development. Charles A. Nelson III of Harvard Medical School and Boston Children's Hospital described his longitudinal study of how the brain responds to severe neglect.

Launched in 1989, the ongoing study has followed 136 institutionalized children and 72 never-institutionalized children in Bulgaria and found long-lasting differences in brain activation. Institutionalized children showed greatly diminished EEG activity in the frontal cortex, as well as less grey and white matter and reduced brain connectivity. Children placed in foster care by age 2 had normal EEG activity when tested at age 8, but those placed in foster care later showed no improvement in EGG activity. Some measures of white matter integrity and connectivity improved in the early foster care group, but others did not. Institutionalized children also had elevated heart rate and cortisol responses to stress, while those in foster care by age 2 showed a pattern closer to never-institutionalized children. These data point to a sensitive period in early childhood when some recovery from the effects of stress can be achieved.

Institutionalized children have much lower EEG activity than children who have never been institutionalized. (Image courtesy of Charles A. Nelson III)

Nelson outlined several complications in interpreting these results. The mechanisms underlying the changes in EEG activity and grey and white matter loss are unknown, and because of the relatively small sample size it is difficult to draw conclusions about critical-period timing. It is also unclear how representative children raised in institutions are to the general population of children raised in poverty. Finally, the researchers had little to no information on prenatal factors such as nutrition or exposure to toxic substances, and therefore could not control for them.

Nelson called for more longitudinal studies of interventions to examine how children recover from early deprivation. Because of the difficulty in studying underlying biological mechanisms in humans, animal models would also move the field forward.

Discussion

In the discussion at the end of the session, speakers were asked how practitioners who work with socioeconomically disadvantaged children and families can put research findings into practice. They recommended encouraging parents to invest in children's development through talking and reading. Yet they acknowledged that barriers such as parents' depression or psychiatric illness, or simply time constraints, could stymie such efforts. Tottenham spoke about findings linking young children's environment, brain processes, and phenotypic traits. Farah argued that basic research in neuroscience must be translated into interventions that can be assessed for efficacy.

In response to a question about conducting studies in low-income countries, Nelson noted that his mandate is to do just that. His group uses portable tools such as high-density EEG and eye-tracking devices that are waterproof and shockproof to reach these populations.

The panelists also discussed the possibility of interventions for older children. Nelson said that executive functions, governed by the prefrontal cortex, should be targeted because they have the longest developmental trajectory. However, it is unclear which domains could be rescued after the critical period for their development had passed.

Highlights

Growth is used as a health measure worldwide, but there is a need to develop internationally applicable measures for other aspects of child development.

Stunting afflicts 24% of children under 5 years old worldwide and has stark long-term effects neurologically, cognitively, and economically.

Properly timed nutritional interventions may reverse some deficits caused by iron deficiency that were previously thought to be permanent.

Results from a cross-species project of iron deficiency in humans, monkeys, and rats indicated that many long-term deficits previously attributed to iron deficiency in infancy may stem from prenatal iron deficiency—complicating prospects of iron treatment in deficient children.

Standardizing nutritional status biomarkers

Physical growth in children is perhaps the most common health measure used worldwide. Growth is easy to measure repeatedly and is equivalent across contexts; it is also a marker for environmental deprivation and for cognition and other aspects of development. Edward A. Frongillo of the University of South Carolina discussed the need to standardize biomarkers for nutrition and other aspects of early childhood development and to develop the tools to assess them.

Current growth standards for children emerged from a 1995 World Health Organization plan to replace old references, which were based on primarily bottle-fed infants in the U.S. and thus did not apply to healthy breast-fed infants. The new standards describe how children grow under optimal conditions and were designed by sampling from six countries. Since the implementation of the new standards in 2006, policy makers' interest in nutrition has grown dramatically, and wealthy countries are considering large-scale investments to eliminate stunting caused by nutritional deprivation.

Because studies on stunting have concluded that deprivation affects growth between conception and age 2, policy efforts focus on this timeframe. However, Leroy, Frongillo, and colleagues recently reported that 30% of the growth deficit of children under 5 years old occurs after age 2, suggesting that attention should be paid to the 2- to 5-year-old age group in addition to the current focus on conception to age 2.

Frongillo said researchers should devise internationally applicable measures and indicators for aspects of development besides growth—such as cognitive and language skills and social and emotional development—particularly ones that are validated in low- and middle-income countries and scalable to large sample sizes.

The most useful biomarkers for optimal childhood development

Growth and micronutrient status are clear biomarkers of nutritional adequacy, explained Maureen M. Black of the University of Maryland School of Medicine. Although the number of children who are stunted because of nutritional deprivation is falling, according to UNICEF data the condition afflicts 25% of children under 5 years old worldwide—161 million children.

Stunting has stark long-term effects neurologically, cognitively, and economically. It has been linked with low IQ scores, poorer academic performance, early marriage, and less earning capacity, thus taking a toll not just on individuals but also on communities. Our knowledge about brain development suggests that early intervention to promote optimal brain functioning is most effective, but trials attempting to treat or prevent the effects of nutritional deprivation have shown inconsistent results.

Stunting interferes with normal brain development. (Image courtesy of Maureen M. Black)

These inconsistencies could result from children having multiple deficiencies, and it is often unclear how to intervene. Epigenetic changes at the time of conception could also be at play. Another key and often ignored factor in the efficacy of an intervention is the context in which it is delivered. For example, in a study in rural India, 6 months of micronutrient supplementation improved iron status and growth, but school performance and language development improved only for children in low-quality schools, not for those in high-quality schools. Interventions integrating nutrition with other aspects of child development, such as cognition and language skills, are likely to have the best chance for success.

Timing interventions to optimize brain development

Different brain regions and processes have different developmental trajectories, so timing is crucial in nutritional interventions. Michael K. Georgieff of the University of Minnesota demonstrated the importance of timing in an intervention previously thought to be ineffective. Fetal and neonatal iron deficiency suppresses synapse formation and plasticity in the hippocampus and has been strongly linked to long-term neurodevelopmental changes. Until recently, researchers thought certain effects of early-life iron deficiency were permanent and could not be ameliorated, but Georgieff's work suggests that properly timed interventions may be effective.

In a mouse model, his lab reversibly disabled iron uptake in fetal hippocampal neurons during late gestation. In adulthood, the mice had improperly formed hippocampal dendrites and performed poorly on the Morris water maze, a hippocampus-linked memory task. Hippocampal dendrite formation peaks at 3 weeks of age; restoring iron uptake before then led to restoration of both dendritic architecture and Morris maze performance. Restoring iron uptake later had no benefit to structure, behavior, or gene expression.

The hippocampus of control animals (A, C, and E) shows orderly dendritic connections (red arrows). In the absence of iron uptake in hippocampal neurons, dendritic connections become disordered (B, blue arrow). When iron is restored at postnatal day 21 (C), dendritic connections return to normal. But when iron uptake is restored later, at postnatal day 42 (D), there is no effect. The bar graphs (bottom) show corresponding performance on the Morris water maze, indicating a restoration in hippocampal memory. (Image courtesy of Michael K. Georgieff)

Next, Georgieff's team examined whether the negative brain effects of iron deficiency can be tempered or ameliorated with the nutrient choline, which improves electrophysiological, morphological, and functional deficits in early rodent brain development through neurotransmitter-mediated and epigenetic mechanisms. Giving choline to iron-deficient pregnant rats partially improved memory deficits in their offspring by adulthood. The intervention normalized the expression of a gene important in hippocampal function, potentially mediated by epigenetic mechanisms.

A paradigm for interdisciplinary approaches to nutritional neuroscience

According to the World Health Organization, iron is among the most common nutrient deficiencies. One quarter of the world's infants have an iron deficiency severe enough to cause anemia, but treating children with iron has not reversed cognitive, motor, and social-emotional alterations. To investigate why, Betsy Lozoff of the University of Michigan and a multi-institutional team of colleagues conducted a 10-year investigation of the effects of iron depletion on brain and behavior, as well as its timing, duration, and potential for intervention.

The study assessed brain chemistry, structure, and anatomy, as well as cognitive, sensory-motor, and social domains in rats, monkeys, and humans. Iron deficiency negatively affected neurodevelopment even when not severe enough to cause anemia. In animal models, iron deficiency altered brain structure and function and genomic and proteomic profiles. These findings are clinically important, Lozoff told the audience, because pediatricians only screen for anemia. Giving iron at the equivalent of later infancy—when pediatricians would administer it—did not ameliorate deficits.

The research also pointed to the conclusion that long-term deficits previously attributed to iron deficiency in later infancy may have also stemmed from iron deficiency during gestation (prenatally). Iron supplementation beginning at birth in humans—or the equivalent developmental time in animal models—did not prevent deficits in later infancy. Furthermore, rapid neonatal repletion in the developing rat with an amount of iron equivalent to the high-end used in clinical pediatric care was as detrimental as the deficiency itself. Researchers should look for better ways to deliver iron to the developing brain, as well as adjunct therapies that can ameliorate the effects of iron deficiency, Lozoff concluded.

Discussion

The speakers emphasized that correcting anemia and blood measures of iron deficiency differs from correcting brain iron and the effects of deficiency on the developing central nervous system. Blood measures of iron deficiency readily respond to iron treatment, but it is still unclear how best to provide timely, adequate iron to the developing brain. The research summarized points to the critical importance of iron nutriture during gestation. However, despite recommendations for iron supplementation during pregnancy, many infants worldwide are born iron-depleted. Furthermore, the fetal brain may be iron-deficient in common clinical conditions when the mother may be iron-sufficient, such as diabetes during pregnancy or intrauterine growth restriction, which is often caused by hypertension.

The speakers also discussed areas of nutrition-related research still in their infancy, such as nutrigenomics and microbiome studies. For example, different gene variants might cause certain nutrients to be more effectively taken up than others. Research into how these mechanisms work needs to be completed and then tested in the field.

Speakers raised the need for better methods to study the effects of nutrition on human brain development. Current brain-based measures generally involve sophisticated technologies that are difficult to apply in the settings where nutrient deficiencies are most widespread. Furthermore, many of the most sensitive measures are not standardized. Classic neurological research is often based on a clear deficit, such as an inability to speak after a stroke, but nutrients have subtler effects that are harder to detect but may nonetheless affect function in daily life.

Highlights

Investigating the trajectory of myelination alongside the maturation of the cortex in the infant brain may shed light on typical and atypical brain development.

In mice, eating a diet high in fats and branched-chain amino acids during pregnancy had negative effects on offspring, particularly males.

Access to clean drinking water and sanitation did not improve language scores in children in Ethiopia, India, Peru, and Vietnam.

Training family day care providers to be more responsive to children led to improved executive function in younger but not older children.

The Center for Nutrition, Learning, and Memory at the University of Illinois, Urbana–Champaign, studies the effects of nutrition on cognition.

Cortical maturation and white matter myelination in early childhood

Work to map the trajectory of white matter myelination throughout early childhood can shed light on typical and atypical brain development. Elise C. Croteau-Chonka is a graduate student in the Advanced Baby Imaging Laboratory at Brown University, where researchers map myelin in the brains of infants and children using MRI techniques called mcDESPOT, which tracks the presence of water in myelin, and MP-RAGE, which produces high-resolution images. With the help of a protocol that reduces stimuli in the scanner so that children can undergo the procedure while sleeping, the lab has collected the largest white matter data set available in such young children.

Croteau-Chonka is using these techniques to probe the relationship between cortical development and myelin maturation in seven cortical regions that are either slow-, moderate-, or fast-developing. These processes are correlated but seem to have a temporal offset, which may have significance for their roles in typical and atypical development.

The myelin water fraction correlates with histological measures of myelin content. (Image courtesy of Elise C. Croteau-Chonka)

Western diets, postpartum depression, and developmental programming

Health risks associated with obesity may be mediated by increased inflammation, which during pregnancy may impact both maternal mental health and metabolic programming in fetal development. Jessica L. Bolton, a graduate student at Duke University, studied how high- and low-fat maternal diets affect offspring in mice. Half of the animals in each group also received chow enriched with branched-chain amino acids (BCAAs), which are abundant in meat and dairy and thought to have proinflammatory properties. The study began 6 weeks before breeding and continued through gestation and lactation.

The high-fat BCAA diet, which is comparable to a Western diet, caused by far the most weight gain in mothers, and increased inflammation and postpartum depression–like behaviors. Offspring had decreased birth weight, altered immune cell expression in the brain, and increased anxiety. Males exhibited hyperactivity in adulthood. Maternal high-fat diets (without BCAA) had the most deleterious effects on offspring. This study was designed to complement an ongoing clinical trial on diet and maternal well-being in humans led by researchers at Duke University.

Water and sanitation interventions

Access to clean water and sanitation services is associated with improved cognition, perhaps because these facilities curb infection and infestation rates and promote growth. Kirk A. Dearden of the Center for Global Health and Development at Boston University studied 8000 children in Ethiopia, India, Peru, and Vietnam to investigate whether improved access to drinking water at 1, 5, and 8 years old correlates with improved language scores.

The researchers enrolled children at 6–17 months old and followed up at 4–5 and 7–8 years old. In models adjusted to account for factors like sex, age, and schooling, the team did not observe language improvement in children with better access to sanitation. However, some improvements were observed when communities as a whole had better access.

Dearden discussed the need for longitudinal studies on this topic. More information about how sanitation affects cognition, through mechanisms such as inflammation or illness, would also be helpful. So far, there is limited evidence for investing scarce resources in water, sanitation, or hygiene interventions.

Responsive caregiving and executive function

Socioeconomically disadvantaged children are often exposed to low-quality non-parental care that is associated with lower executive function. Emily C. Merz, a postdoctoral associate in the Neurocognition, Early Experience, and Development Lab at Columbia University, is studying whether training family day care providers to be more responsive to children could ameliorate this effect.

The study followed 57 child care providers and 131 children aged 2.5–5 years old. The providers took a 20-session online course that focused on how to stay attuned to children's cues, help children maintain attention, and provide rich language stimulation. The researchers assessed children's executive function by measuring impulse control, conflict inhibition (the ability to act in a way that is contrary to the dominant response), and parent-reported attention problems.

Completing the online course improved providers' teaching scores. The intervention did not affect the behavior of older children, but younger children whose providers took the course showed better impulse control and fewer attention problems. Since most children in family day care are infants and toddlers, the intervention may help reduce socioeconomic disparities in developing self-control and regulating attention.

A public–private partnership to study nutritional enhancement of learning and memory

The conference included two lectures sponsored by Abbott Nutrition, delivered by codirectors of the Center for Nutrition, Learning, and Memory (CNLM) at the University of Illinois, Urbana–Champaign, Keith A. Garleb of Abbott Nutrition and Neal J. Cohen, a professor at the university. The center studies the effects of nutrition on cognition. Funded through an initial 5-year, $50 million commitment from Abbott Nutrition, the project functions as an annual solicited research competition, with 86 researchers, 16 departments, and 6 colleges at the university participating.

Major goals include measuring the cognitive effects of nutritional interventions and identifying the underlying mechanisms of action. The center collaborates with institutions around the world, including the U.S. military, which has a strong interest in nutritional interventions that can improve, enhance, or maintain cognitive performance and mitigate the effects of traumatic brain injury.

Although the brain has critical periods for cognitive development, memory is plastic throughout life and modifiable by multiple factors, including exercise and nutrition. The hippocampus is an especially attractive target for studying memory-enhancing factors because it continues to produce new neurons and is highly sensitive to experience.

The hippocampus governs relational memory, which links the who, what, where, and when of events. Cohen described sensitive tests devised by CNLM researchers to measure changes in this hippocampal function. In one test, subjects shown a series of faces paired with scenes must later match up the pairs. Researchers can measure response with eye tracking, and the test is reliable in everyone from babies to older adults with Alzheimer's disease. In children and young adults, physical fitness correlated with better relational memory.

CNLM researchers are also monitoring changes in health status, brain connectivity, metabolism, biochemistry, and other factors in relation to nutrition and fitness, as well as using optical imaging to longitudinally study brain networks in babies.

Highlights

Minding the Baby is a program that aims to help young first-time parents form strong attachments to their babies and overcome their own history of adversity.

The Thirty Million Words Initiative encourages parent talk as a lever to build the parent–child relationship and improve children's development.

Early childhood development programs across the U.S. are a patchwork system marred by inequalities in access, inconsistencies in quality, and inefficiencies in administration.

Translating the neuroscience of parenting into interventions for parents: Minding the Baby

The transition to parenthood is a key adult developmental phase, accompanied by a reorganization of neural circuits that balance reward and stress, explained Linda C. Mayes of the Yale School of Medicine. Parents may also be carrying the long-term effects of their own early exposure to adversity or stress. Therefore, interventions for high-risk children must also build adult capacity.

The negative effects on young parents of their own early-life adversity can propel disparities in health and development across generations. (Image courtesy of Linda C. Mayes)

Mayes and her colleagues designed a parent program called Minding the Baby, which has a two-pronged focus on emotional awareness and social connectedness. Parents participate from pregnancy until their child's second birthday and receive 3 to 4 visits from a nurse or social worker each month. The goals are to provide parents with relationships that will help buffer toxic stress, to teach healthy lifestyle habits, and to promote attachment between parents and children by guiding parents to reflect on their child's feelings, needs, and wishes in everyday interactions.

In a randomized controlled trial, the intervention led to higher rates of immunization in children, lower rates of rapid subsequent childbearing, lower rates of child protection referral, and higher rates of attachment. At age 5, children whose parents had participated showed fewer behavioral problems.

On the basis of this trial the program has been nominated as a federally recognized intervention. As they continue to evaluate the program, the researchers plan to include additional health variables and to follow children into early adolescence. The trial is also being replicated internationally.

Intervention to help close the word gap

As a surgeon running a cochlear implant program for children with profound hearing loss, Dana Suskind at University of Chicago Medicine noticed that some of her patients developed age-appropriate speaking and reading skills, while others were barely able to communicate—and the difference fell along socioeconomic lines. She linked her observation to a well-known 1995 study by Betty Hart and Todd Risely reporting that by their fourth birthday, children living in poverty hear 30 million fewer words than their peers.

Suskind launched the Thirty Million Words Initiative, which is developing a set of coordinated behavioral interventions that use parent talk as a lever to build the parent–child relationship. The program rests on the premises that intelligence is malleable and children are made smarter through parent interaction. Parents are also shown the science demonstrating how language promotes brain development.

The organization's flagship program is a 12-week, computer-based home visit curriculum. Researchers and parents use a device called LENA, which is like a language pedometer, to get feedback on language elements including adult word count and conversational turns per hour. A small randomized controlled trial 2 years ago found a significant increase in those and other features of language interaction in parents who had completed the curriculum.

The researchers are beginning a 5-year longitudinal study to test the efficacy of the home visitor curriculum with 200 Early Head Start families. The study will use measures such as oral language, school readiness, and executive function in children, as well as changes in parent behavior, to assess the impact of the curriculum on children’s language and cognitive development. They are also adapting the program for broader use through the public health infrastructure to achieve population-level intervention.

Building early childhood systems: advancing quality, equity, and sustainability

The poor state of early childhood development (ECD) programs in the U.S. is a legacy of the country's founding principles. Sharon Lynn Kagan of Columbia University and Yale University asserted that the national belief in independence has minimized the role for government ECD programs and created a landscape of projects fragmented across state and federal agencies. The embrace of localism has limited the development of national policies on quality, regulation, and funding of ECD programs. And support for entrepreneurialism means that most child care occurs in the private sector.

The outcome is tremendous inequalities in access, inconsistencies in quality, and inefficiencies in programming, differentiating early childhood education from later schooling, Kagan reported. Socioeconomically disadvantaged children attend preschool at lower rates than wealthier children—often in programs with larger class sizes and less attention to school preparation. Quality is spotty—few preschool teachers have a college degree—and monitoring requirements vary widely. Finally, no single entity governs these programs, leading to redundancies in administration and inconsistent funding.

Kagan proposed a plan that would merge existing programs with infrastructure to bring coherence to the field. She envisioned an integrated 8-component system encompassing high-quality education, regulation, and administration; parental and community engagement; and a strong link to the school system.

Discussion

Speakers discussed what a successful early childhood intervention would be; no metrics to assess such success exist. Mayes pointed to less disparity in access to early child care and a general acceptance that relationships between parents and children matter, while Kagan stressed the need for an equitable system in which quality mental health services are available. Suskind noted that such changes are not short-term but generational, as evidenced by how much more cognitively-based society is today compared to 150 years ago.

The discussion also covered the messaging needed to get child development interventions onto the public agenda. Minding the Baby is supported by state and private philanthropy, Mayes reported, but her team is also working with business colleagues to establish sustainable funding. Building a public platform involved framing messages about early childhood development in ways that make sense to policy makers.

These efforts have largely focused on individual programs, but a broader case for early childhood development is needed, Kegan argued. If the discourse stresses helping at-risk children, policy makers could insist that doing so is not society's responsibility but the family's. It is better to frame the issue in terms of giving every child the means to succeed.

Panel: policy making to advance early childhood development

The conference closed with a panel discussion, moderated by Pia Britto of UNICEF, that looked at how to shape policy to address multiple adversities in early childhood development. Although more countries are moving into middle-income status, economic and health disparities are growing. Early childhood programs are popping up piecemeal around the world, and now is the time to bring brain research to bear on these efforts.

Indeed, as Claudia Gonzalez, also at UNICEF, advocated, the early childhood field must harness society's enormous interest in neuroscience to create an advocacy strategy for early childhood development. The role of neuroscientists must go beyond publishing papers. Scientists also need to display the real-world implications of findings to show policy makers, parents, and the media how brain-based investment in early childhood development will lead to smarter, healthier, and happier children. Local examples of successful programs should be elevated to the national level to raise awareness. Because children do not vote, it can be difficult to bring them onto the political agenda, she noted. UNICEF plans to create an international early childhood council of high-profile ambassadors to champion the issue.

James M. Perrin of the American Academy of Pediatrics said that pediatricians are moving from a solely medical focus to an integrated one, in which they work closely with health and community practitioners to take on poverty-related issues such as mental health and environmental risks, to endorse economic policies that help families, and to collaborate with projects that build health literacy.

Panelists also outlined the role of federal and local government. Linda K. Smith from the U.S. Department of Health and Human Services reported that the agency is investing heavily in early childhood, primarily by partnering with state and local government and providing incentives to create pre-kindergarten programs. She stressed the agency's commitment to science as the driver of policy, noting its recent investment in two major nationwide studies. Sophia Pappas of the New York City Department of Education reported that the city is actively recruiting for and preparing its universal preschool for 4-year-olds. Britto closed the session by urging researchers at the meeting to expand their work to low- and middle-income countries.

What are the timeframes for critical periods in cognitive, emotional, and other types of development?

Can the detrimental effects of deprivation during early childhood be reversed?

What are the dangers of manipulating critical periods for therapeutic purposes?

Should interventions be available to all children who experience or are at risk of early adversity or should they be targeted in some way?

How can research on brain development in children be used to combat negative self-identity and stereotypes?

How are epigenetic mechanisms contributing to the effects of childhood adversity?

What kinds of internationally standardized child development measures would best translate research on brain development into science-based policies?

How can local communities and government agencies work together to improve child care, both in the U.S. and internationally?