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What’s the brain got to do with it?

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What is translational neuroscience? The new field of translational neuroscience uses brain science to inform applications that improve health and well-being. This means using (or improving) our understanding of the brain in order to develop new strategies for intervention. Until recently, translational neuroscience has supported medical interventions that are clinic-based, as in pharmacological, surgical, or behavioral treatments for neural and neuropsychiatric disorders. New on the horizon, however, is the use of neuroscience perspectives to inform social and behavioral interventions that are ecologically-based and can be delivered in the home or school setting. The target of these interventions has expanded to include developmental health outcomes, school readiness, and health promotion, in addition to brain-based disorders. This new approach takes translational neuroscience out of the clinic and puts it to work in our communities.

This series of short articles will present some of the possibilities inherent in this new perspective on translational neuroscience. We invite you to join us in exploring the promise of this approach.

photo credit: Gavin Bell

What’s the brain got to do with it? Everything. This is because the brain is the critical mechanism linking the presentation of a stimulus and production of a complex behavioral response. Let’s say that you suddenly see a tiger bounding down the sidewalk in your direction. Your brain processes the sensory information: the stripes, the snarl, the catness, and the size of the approaching animal. Your brain interprets this information as danger and produces a survival response – your heart races, your blood pressure spikes, and you dive into the nearest open doorway. Without the neural processing of sensory input, you cannot be aware of your danger (the sight and sound of the oncoming tiger) or the possibility of escape (the open doorway). Without the brain’s emotional and cognitive processing of this sensory information, you cannot mobilize your body’s emergency energy resources or plan your own rescue. Without connections between your brain’s motor processing systems and your muscles, you cannot produce life-saving behavior. Without a brain, you are tiger food.

Not only is your behavior affected by your encounter with the tiger, so is your brain and the rest of your body. In large and small ways, your brain is impacted by life events and by your environment, and this, in turn, affects what you do and how your body works. Research has demonstrated that major, potentially traumatic stressors (such as tiger attacks) may have long-term effects on brain structure, brain and body function, and behavior -- even after just one event (Ganzel et al., 2008). Other work has demonstrated that more subtle, pervasive, and/or chronic stressors (such as poverty or growing up in a chaotic household) can also impact your brain and body - including decreasing your immune response (Gianaros et al., 2007; Taylor et al., 2006).

The brain, stress, and health. Whether stress comes in a single awful episode or a chronic grind, research has demonstrated that there is a strong link between stress and poor health. Recent thinking identifies the brain as a big part of that link (Ganzel et al., 2010; McEwen, 2007). Research suggests that stress can cause “wear and tear” in the brain areas most responsive to stressors; these are the brain areas that are on the front lines of saving your life from the tiger or keeping you going during the long illness of a loved one. Over time, the “wear and tear” in these regions can reshape your brain. In doing so, it is reshaping your body’s response to the next stressor.

For example, there is expanding evidence that accumulated stress decreases the size of the human prefrontal cortex in areas that underlie executive function, even in people who do not have a mental disorder (Ansell et al., 2012; Ganzel et al., 2008). These particular brain areas serve as the “air-traffic control” for emotion, cognition, and behavior, so that emotion regulation, cognitive control, and behavioral inhibition are likely to be affected. These brain areas also regulate physiological stress responses in the periphery of the body, including stress-related changes in heart rate, blood pressure, and immune function (Lane & Wager, 2009).

We are only beginning to learn what happens when stress remodels these brain areas. However, this work is likely to shed light on the mechanisms that link cumulative risk and cognitive impairment, neighborhood violence and child social-emotional adaptation, poverty and ill health, among very many important questions. An understanding of the impact of environmental risk on the brain may be a critical step towards improving and assessing existing therapeutic interventions, and developing new, better-targeted ones. This is important new ground for translational neuroscience.

Vulnerability and opportunity in the developing brain. We are learning more every day about how the brain works, how it develops, and how its development affects how it works.

neurons in culture, photo credit: M.R. McGill

In humans, the central nervous system begins to form during the first few months of fetal development. At birth, the human brain has approximately 100 billion neurons (about as many neurons as there are stars in our galaxy). Although all neurons develop through the same stages, different brain regions develop according to different timetables. For example, maturation in the frontal cortex starts in the motor area (involved in the execution of bodily movement) and ends with maturation of the dorsolateral prefrontal cortex (DLPFC) in early adulthood (Giedd et al., 1996). The DLPFC is a high-level association area and is one of those brain regions that play a critical role in planning, executive function, and emotion regulation.

The processes of neural development make the brain temporarily more malleable, so that the developing brain can be more vulnerable to insult or more open to positive influences. And because different brain areas have different developmental trajectories, these windows of vulnerability and/or opportunity vary across brain region, as well as across development. Thus, the impact of a stressor or an intervention is likely to quantitatively and/or qualitatively change as a function of developmental timing (Ganzel & Morris, 2011).

Neuro-example #1:The developmental timing of child sexual abuse.

This point is illustrated by a study conducted by Susan Andersen and Martin Teicher from the Harvard Medical School (Andersen et al., 2008). This study used magnetic resonance imaging (MRI) and structural equation modeling to compare regional differences in brain structure in young women who had experienced child sexual abuse (CSA) at different ages, relative to a comparison group that had not experienced CSA.

Women who were abused as preschoolers (between the ages of three and five) showed the greatest reduction in brain volume in a region called the hippocampus, which serves to restrain the hypothalamic-pituitary-adrenal axis (which produces the powerful stress hormone cortisol), as well as playing an important role in the consolidation of long-term memory. These women were also more likely to be currently depressed than women in the comparison group or women who had been abused during any other developmental period.

By contrast, women who had experienced CSA between the ages of nine and ten had smaller volumes of the frontal portion of the corpus callosum, which is the white matter that conveys information between the hemispheres of the brain. These women were more likely to have current symptoms of posttraumatic stress disorder than women in any other group. CSA occurring between the ages of 11 and 13 was again associated with smaller hippocampal volume, but the effect was not as strong as among those women who were abused as preschoolers. Finally, women experiencing child sexual abuse between the ages of 14 and 16 showed reduced volume in prefrontal cortex, which is consistent with ongoing development in this brain area in later adolescence.

This example suggests that developmental timing plays an important role in how (and where) stress might impact the developing brain, with distinctive patterns of long-term consequences for health. There is a large body of research using animal and human models that examines the effect of very early stress on brain, behavior, and health. However, the broader role of developmental timing (i.e., spanning all of development) remains relatively unexplored and may provide important information to guide intervention.

Neuro-example #2: The developmental timing of intervention.

If the developmental timing of stress matters for health outcomes, does the developmental timing of interventions matter, too? We turn to neuroscientific studies of animals to see the direct effects of developmental timing on interventions.

An established body of research has shown that increasing or decreasing the quality of maternal care given to a laboratory rat pup in its first week of life can have permanent consequences for that pup’s cognitive abilities and the neural basis of its stress response (Diorio & Meaney, 2007). This research is often cited in support of interventions that target children ages “zero to three.”

Interestingly, many of the physiological and behavioral deficits associated with low quality early maternal care can be reversed by providing these pups with enriched environments during adolescence (Bredy et al., 2004). Environmental enrichment that occurs earlier or later than adolescence does not have the same beneficial effects. Moreover, enrichment during adolescence also helps to reverse the consequences of other early environmental insults, such as prenatal maternal stress, extended postnatal maternal separation, and early lead exposure. Notably, though, adolescent environmental enrichment does not have an effect on the brains or behavior of pups that had normal early environments and good maternal care. Only the pups at risk benefited from the enrichment intervention during adolescence.

 

These studies suggest the need for considering brain development when determining the type and timing of interventions. Awareness that different brain regions develop according to different timetables may allow us to target our interventions to take best advantage of the natural plasticity inherent in the developing brain.

This is the first of a series of brief articles in which we explore some of the possibilities inherent in these new and broader perspectives on translational neuroscience. We invite you to join us in future articles as we look at how an interdisciplinary perspective that bridges the social and life sciences can inform intervention in support of children and families at risk. In our next installment, we will explore how normal brain maturation has entered the practice and policy arena, such as the 2005 Supreme Court ruling prohibiting death penalty for juveniles. More soon!

 

Dr. Barbara Ganzel, Director, Laboratory for Lifespan Affective Neuroscience
blg4@cornell.edu

 

 

 

References

Andersen, S. L., Tomada, A., Vincow, E. S., Valente, E., Polcari, A., & Teicher, M. H. (2008). Preliminary evidence for sensitive periods in the effect of childhood sexual abuse on regional brain development. Journal of Neuropsychiatry and Clinical Neurosciences, 20, 292–301.

Ansell, E.B., Rando, K., Tuit, K., Guarnaccia, J., & Sinha, R. (2012). Cumulative adversity and smaller gray matter volume in medial prefrontal, anterior cingulate, and insula regions. Biological Psychiatry, 72(1), 57-64.

Bredy, T. W., Zhang, T. Y., Grant, R. J., Diorio, J., & Meaney, M. J. (2004). Peripubertal environmental enrichment reverses the effects of maternal care on hippocampal development and glutamate receptor subunit expression. European Journal of Neuroscience, 20, 1355–1362.

Diorio, J., & Meaney, M. J. (2007). Maternal programming of defensive responses through sustained effects on gene expression. Journal of Psychiatry Neuroscience, 32, 275–284.

Ganzel, B., Kim, P., Glover, G., & Temple, E. (2008). Resilience after 9/11: Multimodal neuroimaging evidence for stress-related change in the healthy adult brain. NeuroImage, 40, 788-795.

Ganzel., B. & Morris, P. (2011). Allostasis and the developing human brain: Explicit consideration of implicit models. Development & Psychopathology, 23, 953-974.

Ganzel, B., Morris, P., & Wethington, E. (2010). Allostasis and the human brain: Integrating models of stress from the social and life sciences. Psychological Review, 117, 134-174.

Gianaros, P. J., Horenstein, J. A., Cohen, S., Matthews, K. A., Brown, S. M., Flory, J. D., . . . Hariri, A. R. (2007). Perigenual anterior cingulate morphology covaries with perceived social standing. Social Cognition and Affective Neuroscience, 2, 161–173.

Gogtay, N., Giedd, J. N., Lusk, L., Hayashi, K. M., Greenstein, D., Vaituzis, A. C., et al. (2004). Dynamic mapping of human cortical development during childhood through early adulthood. Proceedings of the National Academy of Sciences of the United States of America, 101, 8174–8179.

Lane, R. D., & Wager, T. D. (2009). The new field of brain-body medicine: What have we learned and where are we headed? NeuroImage, 47, 1135–1140.

McEwen, B. S. (2007). Physiology and neurobiology of stress and adaptation: Central role of the brain. Physiological Reviews, 87, 873–901.

Taylor, S. E., Eisenberger, N. I., Saxbe, D., Lehman, B. J., & Lieberman, M. D. (2006). Neural responses to emotional stimuli are associated with childhood family stress. Biological Psychiatry, 60, 296–301.

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