Early Life Experience, Critical Periods, and Brain Development

It’s long been known that childhood experiences have the power to alter brain development, ultimately influencing the adults that children will one day become. Martha Farah, a neuroscientist from the University of Pennsylvania and member of the Dana Alliance for Brain Initiatives (DABI), says that even our grandmothers have been aware of this—even though most wouldn’t have considered changes to neural circuits, neurotransmitter levels or receptor densities as part of their explanation for the phenomenon.

“Children’s early experience shape their whole life trajectories. Even experiences before birth, the conditions that the mother lives in while she’s pregnant, can make changes. And you don’t have to be a neuroscientist to know that these factors can influence one’s whole life,” she says. “But what scientists are just beginning to unravel are the mechanisms by which these changes happen. They are starting to understand how early life experiences get translated into changes in the brain and behavior.”

Research presented the Society for Neuroscience’s annual meeting in Washington, DC, sheds some light on some of those translation mechanisms—and may help to define critical periods of development that we could one day act upon to get abnormally developing brain circuits back on track.

Maltreatment alters regulatory circuits

There is ample evidence that childhood maltreatment is linked to later neuropsychiatric issues in adulthood, including depression, anxiety, and impulse control problems. To better understand this link, Elizabeth Cox and colleagues at Yale University wanted to look at whether physical and emotional abuse influenced the development of the prefrontal cortex, the region of the brain responsible for emotional regulation and self-control.

“Previous studies have shown that child maltreatment is associated with altered volume in brain regions involved in regulating emotions and impulses, as well as alterations in how these regions function,” says Cox. “But while studies suggest that changes within these circuits are present by adolescence, it’s not known whether these changes occur prior to adolescence or whether they emerge during adolescence, a critical period in development.”

To try to answer that question, the researchers recruited 44 adolescents and assessed childhood maltreatment using the Childhood Trauma Questionnaire, a psychometric test that looks at both physical abuse, emotional abuse and neglect. They then scanned the study participants using functional magnetic resonance imaging (fMRI)—both at about 15 years of age and then again around 18 years of age—as the participants performed an emotional face processing task. The scans measured brain structure and volume, functional blood flow, and white matter integrity in the critical circuits known to govern impulse control. Participants who had been maltreated in childhood showed significant differences—even when they had only been emotionally neglected.

“We saw that childhood maltreatment is associated with decreases in prefrontal cortex volume—and also saw decreases in the integrity of the white matter, or wiring between these regions. We also saw changes in the way that these regions function, where children who had been maltreated had a decreased response in prefrontal cortex to emotional stimuli,” says Cox. “And when we compare the scans at the different ages, our study suggests these changes associated with maltreatment are occurring during adolescence. And that may give us a window of opportunity where we could offer interventions for preventing some of the outcomes you see in these kids.”

The group also observed an interesting sex difference. “In girls, we saw, over time, greater decreases in functional responses in ventral circuitry that is involved with emotional regulation. In boys, however, we saw greater decreases, over time, in dorsal circuitry involved in impulse control,” she says. “There’s longstanding evidence that girls who are maltreated are more likely to develop depression, while maltreated boys are more likely to develop impulse control problems. While our results are preliminary, these findings may suggest some of the reasons why these differences occur.”

Maternal buffering

Of course, children who aren’t mistreated can develop depression and anxiety disorders later in life. Research by Dylan Gee and colleagues at the University of California Los Angeles (UCLA) suggests that the presence of a devoted caregiver may help bolster the brain circuits involved in emotional regulation, potentially preventing those problems. Gee focused on the circuit connecting the prefrontal cortex and the amygdala, the region of the brain responsible for the “fight or flight” response.

“The connections between the amygdala and the prefrontal cortex regulate emotion. However, we know that these connections mature late in development. Since a caregiver is an important external source of emotional regulation in childhood, buffering against stress and arousal, we wanted to see how they might be influencing the function of this circuit,” she said.

Gee and colleagues recruited 53 children, 23 between ages 4 and 10, and 30 between 11 and 17. They then scanned their brains while the participants viewed a photo of their own mother or a stranger, as well as measured participants’ responses to emotional stimuli while in the presence of their mother or a stranger. Gee says the results were striking.

“We saw that the caregiver buffers against stress reactivity in the amygdala in children—but we did not see the same effect in adolescents,” she says.  The teens showed the same brain response to stress regardless of what photo was shown. “When we examined amygdala prefrontal connectivity, we also found differences. In adolescents we saw a mature connectivity between the prefrontal cortex and amygdala, which we know is important for emotional regulation. In children, however, we saw no significant connectivity between the amygdala and the prefrontal cortex when they viewed the stranger. But when they are viewing their mother, the amygdala-prefrontal circuitry looks like that of an adolescent or adult. That is, the mother seems to physically induce this change in connectivity during the task that may allow for more successful emotional regulation.”

Similarly, during the behavioral task, children made fewer regulatory errors when they sat next to their mothers versus sitting next to strangers. This, Gee argues, suggests that the caregiver may be  acting as an external source of regulation both at the neurobiological and the behavioral levels when a child is exposed to stressful or emotional challenges.

Critical periods, critical interventions

Both studies suggest that there are specific critical periods where clinicians could one day intervene and help get derailed neurodevelopment back on track. And as opposed to a drug, these studies suggest that doctors could target the behavior of parents or healthy, trusted caregivers as environmental interventions. Still, the study authors caution that the work is preliminary—and they need time to follow it through with longitudinal studies before they can offer specific intervention ideas. Farah, however, says despite it being early days, this new research offers exciting new insights into childhood brain development.

“Putting to all together, we see that understanding how early life experiences influence development is complicated. There are gender differences, there are synergies, there are a lot of things to consider,” says Farah. “But, overall, from the molecular level to the network activity of large-scale brain systems, we are beginning to understand the effects of early life experiences on who we later become—and what our chances are for a happy, healthy life as opposed to a troubled one based on those experiences.”