Developmental Neuroscience

Overview

Individual Differences

It is well-known that individual differences in trait expression, personality, and temperament are important in shaping behavioral output in various contexts. These individual factors that play a role in affecting behavior may also underlie and or/predict vulnerabilities to neurodevelopmental and neurospsychiatric disorders, particularly in the face of environmental challenges [1]. Advancements in technology have given rise to several non-invasive techniques for examining individual differences in developing human brains, making it possible to assess properties of cortical- and sub-cortical regions in multiple participants across most stages of development -- thickness, blood flow, shape, and activity patterns of brain areas can be localized and examined during various live experiences. Techniques such as BOLD (blood-oxygen-level dependent imaging) fMRI grant researchers a temporally reliable glimpse of brain function, and have revealed profound variability, not only across stages of development, but across individuals within the same clinically-defined stage of development, varying in both the rate of change over time and the direction of change over time [1,2]. Techniques for controlling for this assortment of variability have identified which specific brain measures may be the best predictors for each stage of development [2].

It was once accepted that the mechanisms of neurodevelopment were orchestrated in a 'blue-print' fashion, with neurons predestined to serve specific functions from conception. However, evidence now points to a more dynamic mode of development, with systems evolving and ever changing to meet new functional demands to subserve the specific neurobiological context into which they are born [3]. Components of these systems include neural progenitor cells, cells from which all neurons and macroglia are created and appear three weeks post-conception and give rise to cell lines in response to timing, molecular signaling, and regional factors; neurons, which are responsible for regulating brain signaling; macroglia, including astrocytes, ogliodendrocytes, ependymal cells; and microglial cells, which all play a role in the formation and maintenance of neural circuitry [3, 4].

Once thought to be involved in passive brain function, the macroglia are directly involved in neuronal function through controlling neurogenesis, synaptogenesis, neurotransmission, plasticity, and neuron growth and survival, all of which may be vulnerable to environmental and experiential pressures [4]. Emerging evidence suggests that individual differences arise from the neural circuitry mediating the functions in which differences have been identified, reflecting functionally relevant variability in biological maturation of circuits or neural connectivity modulated by genetics and/or experience [3]. Cue-driven changes throughout development give rise to cascading processes contributing to individual differences.

[1] Hariri, A. R. (2010). The neurobiology of individual differences in complex behavioral traits. Annual Review of Neuroscience, 32, 225-247.

[2] Brown, T. T. (2016). Individual differences in human brain development. WIREs Cognitive Science 8, e1389.

[3] Jernigan, T. L. & Stiles, J. (2017). Construction of the human forebrain. WIREs Cognitive Science, e1409.

[4] Schitine, C., Nogaroli, L., Costa, M. R., & Hedin-Pereira, C. (2015). Astrocyte heterogeneity in the brain: from development to disease. Frontiers in Cellular Neuroscience, 9, 76.

Disorders

Neurodevelopmental disorders are characterized by a perturbation of the nervous system during development. Aberrant neurodevelopment can lead to neuropsychiatric disorders and impairments in various domains later in life, including motor abilities, cognitive abilities, learning, language, non-verbal communication, and social capabilities. The list of neurodevelopmental disorders includes (among others) autism spectrum disorder, schizophrenia, attention deficit disorder, Rett syndrome, William's syndrome, and fragile X syndrome. Since the 1970s, neurodevelopmental disorders have increased in prevalence - the rate of autism in the 1970s increased from 5 in 10,000 children to 1 in 50 children [1].

Harald Sontheimer (2015) describes the list of neurodevelopmental disorders as "long and heterogeneous," indicating that the expression of symptoms within disorders varies considerably across individuals, and includes disorders with genetic causes and conditions and syndromes that result from insults to the central nervous system during pre- or post-natal development, such as alcohol exposure, nutritional deficiencies, lack of oxygen, infection, fevers, or trauma [2]. Genetic factors have been identified as being associated with a number of the above-mentioned disorders; the associated genes have crucial roles in neuronal migration, synaptogenesis, and axonal growth. These genetic factors or insults can change the structure, function, or connectivity of synapses, and are often comorbid with other disorders. [1, 2].

While neurodevelopmental disorders typically emerge in childhood, the outset of the deviant neural trajectories can be in early embryogenesis, and subsequent development may continue to be off course until from then on, leading to long-lasting behavioral and physiological deficits [3].

Neurodevelopmental disorders can be approached theoretically through both neuroconstructive accounts and neuropsycholohical accounts. The neuropsychological account approaches neurodevelopmental disorders assuming the brain is comprised of independently functioning modules, each module responsible for single cognitive task or grouping of similar tasks. This approach suggests that a perturbation to one of these modules could account for a life-long deficit in the domain for which it is responsible -- for example, if the language module does not develop properly, language deficits can be expected later in life. Conversely, the neuroconstructivist approach considers all interacting and impinging environmental and organizational factors that contribute to the development of an emerging system -- a more neuroholistic approach [4].

[1] Heindel, J., Zoeller, R. T. (2016). Front Matter. Endocrinology: Adult and Pediatric, Elsevier: Amsterdam, Netherlands.

[2] Sontheimer, H. (2015). Central nervous system trauma. Diseases of the Nervous System, Elsevier: Amsterdam, Netherlands

[3] Homoberg, J. R., Kyzar, E. J., Nguyen, M., Norton, W. E., Pittman, J., Poudel, M. K. ... Kalueff, A. V. (2016). Understanding autism and other neurodevelopmental disorder through expeerimental translational neurobehavioral models. Neuroscience and Biobehavioral Reviews, 65,(2016), 292-312.

[4] D'Souza, H. & Karmiloff-Smith, A. (2017). Neurodevelopmental disorders. WIREs Cognitive Science, 8(e1398).

Epigenetics

Epigenetics is the study the interaction between genes and the environment, and the changes in expression of genes caused by experiences with the environment. The work ‘epigenesis’ was used by Aristotle to describe a process explaining how are individual characteristics come into being [1]. The mechanisms by which epigenetics operates involves histone molecule acetylation and methylation, which effectively turn on and off segments of DNA, respectively. These epigenetic mechanisms interact with the environment, and can play an important role in neurodevelopmental reprogramming (altering the development of the brain) [2].

In animals, differing phenotypes can be due to epigenetic mechanisms. For example, dietary changes in the form of supplementation of methyl groups given to pregnant mice of a specific strain causes pups to develop coat color changes and healthy or unhealthy constitutions [3].

Consider the calico cat. Early in female mammal embryo development, epigenetic processes inactivate one of the X chromosomes in cells at random, so X chromosomes in each cell can be different [1]. The calico cat shows this randomization in the color of their coats, reflecting some X chromosomes from both her mother and father having been randomly inactivated, and is a trait that is stable over her lifetime.

In humans, the interaction between genetics and the environment is an important consideration for determining the risk for and trajectory of complex neurodevelopmental disorders (NDDs) like autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) [4]. The phenotypic heterogeneity in these NDDs is determined by the interaction between genetic susceptibility and exposure to environmental risk factors (like chemicals, maternal infection or disease, radiation, or other teratogens), as well as the timing of the teratogen exposure.

Interestingly, the effects of epigenetics can be transgenerational, passing from parent to offspring through the reprogramming of germ cells [4]. These transgenerational effects can depend on whether the mother or father has the trait and whether male or female offspring inherit the trait. For example, exposure to environmental factors like famine can cause prepubescent boys to have children and grandchildren who are more susceptible to certain diseases [5].

[1] Moore, D. S. (2017). Behavioral epigenetics. Wiley Interdisciplinary Reviews. Systems Biology and Medicine, 9(1), doi:10.1002/wsbm.1333

[2] Bale, T. L. (2015). Epigenetic and transgenerational reprogramming of brain development. Nature Reviews. Neuroscience, 16(6), 332-344. doi:10.1038/nrn3818

[3] Cropley, J. E., Dang, T. Y., Martin, D. K., & Suter, C. M. (2012). The penetrance of an epigenetic trait in mice is progressively yet reversibly increased by selection and environment. Proceedings. Biological Sciences, 279(1737), 2347-2353. doi:10.1098/rspb.2011.2646

[4] Lein, P. J. (2015). Overview of the Role of Environmental Factors in Neurodevelopmental Disorders. In Environmental Factors in Neurodevelopmental and Neurodegenerative Disorders (pp. 3-20). Elsevier Inc. doi: 10.1016/B978-0-12-800228-5.00001-7

[5] Kaati, G., Bygren, L. O., & Edvinsson, S. (2002). Cardiovascular and diabetes mortality determined by nutrition during parents' and grandparents' slow growth period. European Journal Of Human Genetics: EJHG, 10(11), 682-688.

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