Johanna Bick, Research Fellow, Boston Children’s Hospital and Harvard Medical School, and Charles A. Nelson, Richard David Scott Chair in Pediatric Developmental Medicine, Boston Children’s Hospital; Professor of Neuroscience and Education, Harvard Medical School and Harvard Graduate School of Education, USA
This article provides an overview of brain development. Starting with four basic principles, it goes on to explain why early experiences have such a powerful role in shaping developmental trajectories and draws attention to the deleterious impact of early adverse experiences on the developing brain. It concludes by discussing evidence suggesting the potential for recovery, both at the level of the brain and in behaviour, and implications for prevention and intervention.
Recent advances in neuroimaging have led to a more nuanced and richer understanding of how the brain develops, starting from the first weeks after conception and continuing until the last years of life. We also know more about how the brain functions and have identified various neural systems that support higher-level emotional, cognitive, and behavioural functioning.
Principle 1: Brain development is a protracted process
Brain development begins shortly after conception and does not reach full maturity until the third decade of life. The neural tube forms a few weeks after conception. Shortly thereafter, cells begin to form, proliferate, and finally migrate to designed locations, which eventually form the various regions of the brain. Once cells reach their final destination, they differentiate into fully functioning neurons and become specialised to their designated brain region. Dendrites, the fibre-like reception areas that support neuronal communication, begin to arborise, allowing nerve cells to communicate with each other. Around the 23rd week of gestation starts a massive overproduction of synapses, or neurochemical signalling points between neurons. This overabundance of synapses eventually becomes reduced through a process known as ‘pruning’, which is heavily based on input from the environment. Here, unused synapses are eliminated, allowing for a fine-tuning and specialisation of the brain. Myelination of axonal fibres is the last stage of brain development. As part of this process, fatty glial cells wrap around axons to insulate neurons, allowing for more efficient neuronal transmission and signalling. The timing of this process varies, with some areas (sensory and motor regions) becoming fully myelinated in the first five years of life and others (frontal regions of the brain) reaching full myelination during early adulthood. For a more detailed review of the processes of brain development, see Tierney and Nelson (2009).
Principle 2: Brains develop within the context of experience
As discussed in the previous section, brain development occurs over decades of life through various stages that build on one another. While genetic forces drive initial stages of prenatal brain development, postnatal brain development occurs via a constant interaction between genes and the environment. Here, genes establish the basic ‘blueprint’ of development, setting the foundation and basic structural plan for the brain. However, the actual ‘construction’ of this plan depends heavily upon signals from the environment. Two of the most experience-dependent processes in the developing brain include the arborisation of dendrites and the pruning of synapses. The density of dendritic branches depends on the amount of and intensity of input from other neurons, with greater dendritic density occurring with greater use. Synaptic connections that are used more often become strengthened, whereas those that are unused are retracted (a phenomenon referred to as ‘use it or lose it’).
While the experience-based nature of brain development is advantageous from an evolutionary perspective, allowing for the brain to develop in the context of the surrounding environment, this degree of ‘plasticity’ comes at a cost if environmental exposures exceed that which brains are designed to handle. Exposures to extreme stress and/or early deprivation are examples of such adverse circumstances. We will discuss specific consequences of each of these atypical experiences in the sections that follow.
Principle 3: Brain development occurs in a hierarchical fashion
Each phase of brain development sets the stage for the subsequent phase; accordingly, more advanced systems depend on the more basic. Therefore, the development of the least complex systems (the brainstem) supports the more complex systems (the circuitry involved in sensory and motor processing) and end with the most sophisticated (cortical and limbic functioning). This has critical implications for development: if adequate signals are not provided for the more basic systems, then the more complex systems, such as those that support emotion and cognitive control or language and memory, cannot develop to their full potential.
Principle 4: The first years of life mark an especially sensitive point in brain development.
Although the brain is moulded by experiences at all phases of life, the experiences during the first years of life have an especially powerful role in influencing the developing brain. Because brain regions vary in the maturation rates, they also vary in the point(s) at which they are maximally sensitive to the environment, or pass through ‘sensitive periods’. Despite varying time courses, the majority of sensitive periods arise during early childhood, making the input received (or not received) during this stage in development critical for ongoing development.
Consequences of early life stress on the developing brain
Healthy brain development depends on expected input from the environment in order to reach its full genetic potential. For example, it is expected that human infants will have access to patterned light and a range of auditory cues, which support the development of visual and auditory systems. It is also expected that infants will have access to a responsive, stable caregiver, which supports the development of a number of systems, including emotional, cognitive, and physical growth. Species-atypical violations of these expected experiences have deleterious consequences for brain development.
One example involves exposure to chronic stress or excessively threatening stimuli, such as when children are reared in maltreating families or exposed to high levels of violence. Prolonged exposure to threat is associated with the activation of the Hypothalamus Pituitary Adrenal (HPA) axis, a primary stress response system in the body. Animal work has shown that chronic exposure to glucocorticoids, the end product of the HPA axis, can have adverse effects on regions of the brain that support memory and learning (the hippocampus), and stress regulation, fear response, and detection of threat (the amygdala). Excessive glucocorticoid exposure has been associated with hyperactivation of the amygdala (Lee et al., 1994; Hatalski et al., 1998) and reduced dendritic spines and dendritic arborisation, resulting in eventual apoptosis of neurons in the hippocampus (Sapolsky, 1996; Kim and Yoon, 1998; Brunson et al., 2001; Ivy et al., 2010). Convergent findings in humans have also been observed in adults with histories of childhood maltreatment (for a review see Hart and Rubia (2012)) and there is some evidence that these neural changes can be observed during childhood (Mehta et al., 2009; Tottenham et al., 2010; McCrory et al., 2013). Human research also suggests that extreme childhood stress leads to alterations in the structural and functional development of portions of the prefrontal cortex, a brain region that supports emotional and cognitive control (Hanson et al., 2010; Edmiston et al., 2011; De Brito et al., 2013).
Psychosocial deprivation is a second form of adversity that can negatively interfere with brain development, especially when it occurs early in life. Childhood exposure to neglect is typically investigated with children reared by neglecting parents in family settings, or at a more extreme level in institutional rearing facilities. Under neglecting circumstances, the brain does not receive adequate environmental input to carry out the normal course of neurodevelopment. This results in an ‘under-wired‘ or ‘mis-wired’ brain, which confers risk for a number of cognitive, emotional and behavioural problems that persist throughout development. Animal models have shown that exposure to chronically depriving or understimulating environments leads to decreased dendritic arborisation and spines in various regions of the cerebral cortex, and is also associated with global reductions in brain volume (Diamond et al., 1966; Globus et al., 1973; Bennett et al., 1996). Parallel findings in humans have also been observed. For example, children reared in depriving circumstances show reductions in overall brain volume (Mehta et al., 2009; Sheridan et al., 2012) and reduced thickness in the cortex (McLaughlin et al., 2014), which may signal atypical trajectories of experience-dependent synaptic pruning. White matter changes are also observed in children exposed to institutional rearing, both on a global level (Sheridan et al., 2012) and in specific axonal bundles associated with emotional and cognitive control (Eluvathingal et al., 2006; Kumar et al., 2014; Bick et al., 2015), suggesting developmental delays in the degree to which neurons become myelinated across development.
Potential for recovery
On a more promising note, the high degree of neural plasticity early in life also allows the brain to be highly sensitive to positive or enriching environments. Therefore, removal from early adversity and entry into a therapeutic context can support recovery. This has been demonstrated on a cellular level in animal work. More complex environments have been shown to lead to more sophisticated dendritic branching and synaptic density in cortical areas (Altman and Das, 1964; Bennett et al., 1964), and have also been associated with larger brain volumes (Rehkamper et al., 1988). Human work involving children removed from conditions of extreme neglect has shown similar findings; for example, institutionally reared children placed into enriching, responsive family settings show structural (Sheridan et al., 2012; Bick et al., 2015) and functional (Vanderwert et al., 2010) improvements of the brain, and associated improvements in cognitive and emotional adjustment (Rutter, 1998; Nelson et al., 2007). For many outcomes, the greatest improvements, both neurally and behaviourally, are typically observed for children who are removed from neglect and provided with enriching environments at the earliest ages (Vanderwert et al., 2010; Rutter, 1998; Nelson et al., 2007).
In summary, there is converging evidence across human and animal studies that early adverse exposure negatively interferes with the developing brain. While excessive exposure to stress may lead to neural alterations due to prolonged exposure to stress hormones, exposure to extreme deprivation may interfere with the brain’s ability to reach its full developmental potential, due to insufficient input. Animal studies have been critical for understanding the consequences of these adverse experiences on a neuronal level. Human studies showing similar morphological and functional alterations have elucidated the consequences for emotional and cognitive functioning. Recent evidence points to the potential for recovery, both in terms of brain structure and function, in early intervention contexts. These studies reinforce the notion that prevention, and early intervention that occurs as early as possible, are likely to lead to the healthiest outcomes in the long term.
Altman, J. and Das, G.D. (1964). Autoradiographic examination of the effects of enriched environment on the rate of glial multiplication in the adult rat brain. Nature 204: 1161–3.
Bennett, E.L., Diamond, M.C., Krech, D. and Rosenzweig, M.R. (1964). Chemical and anatomical plasticity brain. Science 146(3644): 610–19.
Bennett, E.L., Diamond, M.C., Krech, D. and Rosenzweig, M.R. (1996). Chemical and anatomical plasticity of brain. 1964. Journal of Neuropsychiatry and Clinical Neurosciences 8(4): 459–70.
Bick, J., Zhu, T., Stamoulis, C., Fox, N.A., Zeanah, C. and Nelson, C.A. (2015). Effect of early institutionalization and foster care on long-term white matter development: a randomized clinical trial. Journal of the American Medical Association: Pediatrics 169(3): 211–19.
Brunson, K.L., Eghbal-Ahmadi, M., Bender, R., Chen, Y. and Baram, T.Z. (2001). Long-term, progressive hippocampal cell loss and dysfunction induced by early-life administration of corticotropin-releasing hormone reproduce the effects of early-life stress. Proceedings of the National Academy of Sciences of the United States of America 98(15): 8856–61.
De Brito, S.A., Viding, E., Sebastian, C.L., Kelly, P.A., Mechelli, A., Maris, H. et al. (2013). Reduced orbitofrontal and temporal grey matter in a community sample of maltreated children. Journal of Child Psychology and Psychiatry and Allied Disciplines 54(1): 105–12.
Diamond, M.C., Law, F., Rhodes, H., Lindner, B, Rosenzweig, M.R., Krech, D. et al. (1966). Increases in cortical depth and glia numbers in rats subjected to enriched environment. Journal of Comparative Neurolology 128(1): 117–26.
Edmiston, E.E., Wang, F., Mazure, C.M., Guiney, J., Sinha, R., Mayes, L.C. et al. (2011). Corticostriatal-limbic gray matter morphology in adolescents with self-reported exposure to childhood maltreatment. Archives of Pediatrics and Adolescent Medicine 165(12): 1069–77.
Eluvathingal, T.J., Chugani, H.T., Behen, M.E., Juhász, C., Muzik, O., Maqbool, M. et al. (2006). Abnormal brain connectivity in children after early severe socioemotional deprivation: a diffusion tensor imaging study. Pediatrics 117(6): 2093–2100.
Globus, A., Rosenzweig, M.R., Bennett, E.L. and Diamond, M.C. (1973). Effects of differential experience on dendritic spine counts in rat cerebral cortex. Journal of Comparative and Physiological Psychology 82(2): 175–81.
Hanson, J.L., Chung, M.K., Avants, B.B., Shirtcliff, E.A., Gee, J.C., Davidson, R.J. et al. (2010). Early stress is associated with alterations in the orbitofrontal cortex: a tensor-based morphometry investigation of brain structure and behavioral risk. Journal of Neuroscience 30(22): 7466–72.
Hart, H. and Rubia, K. (2012). Neuroimaging of child abuse: a critical review. Frontiers in Human Neuroscience 6: 52.
Hatalski, C.G., Guirguis, C. and Baram, T.Z. (1998). Corticotropin releasing factor mRNA expression in the hypothalamic paraventricular nucleus and the central nucleus of the amygdala is modulated by repeated acute stress in the immature rat. Journal of Neuroendocrinology 10(9): 663–9.
Ivy, A.S., Rex, C.S., Chen, Y., Dubé, C., Maras, P.M., Grigoriadis, D.E. et al. (2010). Hippocampal dysfunction and cognitive impairments provoked by chronic early-life stress involve excessive activation of CRH receptors. Journal of Neuroscience 30(39): 13005–15.
Kim, J.J. and Yoon, K.S. (1998). Stress: metaplastic effects in the hippocampus. Trends in Neurosciences 21(12): 505–9.
Kumar, A., Behen, M.E., Singsoonsud, P., Veenstra, A.L., Wolfe-Christensen, C., Helder, E. et al. (2014). Microstructural abnormalities in language and limbic pathways in orphanage-reared children: a diffusion tensor imaging study. Journal of Child Neurology 29(3): 318–25
Lee, Y., Schulkin, J. and Davis, M. (1994). Effect of corticosterone on the enhancement of the acoustic startle reflex by corticotropin releasing factor (CRF). Brain Research. 666(1): 93–8.
McCrory, E.J., De Brito, S.A., Kelly, P.A., Bird, G., Sebastian, C.L., Mechelli, A. et al. (2013). Amygdala activation in maltreated children during pre-attentive emotional processing. British Journal of Psychiatry 202(4): 269–76.
McLaughlin, K.A., Sheridan, M.A., Winter, W., Fox, N.A., Zeanah, C.H. and Nelson, C.A. (2014). Widespread reductions in cortical thickness following severe early-life deprivation: a neurodevelopmental pathway to attention-deficit/hyperactivity disorder. Biological Psychiatry 76(8): 629–38.
Mehta, M.A., Golembo, N.I., Nosarti, C., Colvert, E., Mota, A., Williams, S.C. et al. (2009). Amygdala, hippocampal and corpus callosum size following severe early institutional deprivation: the English and Romanian Adoptees study pilot. Journal of Child Psychology and Psychiatry and Allied Disciplines 50(8): 943–51.
Nelson, C.A. (2000). The developing brain. In: Shonkoff, J.P. and Phillips, D.A. (eds) From Neurons to Neighborhoods: The science of early child development. Washington DC: National Academy Press.
Nelson, C.A., 3rd, Zeanah, C.H., Fox, N.A., Marshall, P.J., Smyke, A.T. and Guthrie, D. (2007). Cognitive recovery in socially deprived young children: the Bucharest Early Intervention Project. Science. 318(5858): 1937–40.
Rehkamper, G., Haase, E. and Frahm, H.D. (1988). Allometric comparison of brain weight and brain structure volumes in different breeds of the domestic pigeon, Columba livia f.d. (fantails, homing pigeons, strassers). Brain Behavior and Evolution 31(3): 141–9.
Rutter, M. (1998). Developmental catch-up, and deficit, following adoption after severe global early privation. English and Romanian Adoptees (ERA) Study Team. Journal of Child Psychology and Psychiatry and Allied Disciplines 39(4): 465–76.
Sapolsky, R.M. (1996). Stress, glucocorticoids, and damage to the nervous system: the current state of confusion. Stress 1(1): 1–19.
Sheridan, M.A., Fox, N.A., Zeanah, C.H., McLaughlin, K.A. and Nelson, C.A., 3rd. (2012). Variation in neural development as a result of exposure to institutionalization early in childhood. Proceedings of the National Academy of Sciences of the United States of America 109(32): 12927–32.
Tierney, A.L. and Nelson, C.A. 3rd. (2009). Brain development and the role of experience in the early years. Zero Three 30(2): 9–13.
Tottenham, N., Hare, T.A., Quinn, B.T., McCarry, T.W., Nurse, M., Gilhooly, T. et al. (2010). Prolonged institutional rearing is associated with atypically large amygdala volume and difficulties in emotion regulation. Developmental Science 13(1): 46–61.
Vanderwert, R.E., Marshall, P.J., Nelson, C.A., 3rd, Zeanah, C.H. and Fox, N.A. (2010). Timing of intervention affects brain electrical activity in children exposed to severe psychosocial neglect. PLoS One 5(7): e11415.