Unpredictable parental behavior may impair brain circuit formation in infants

UCI researchers say disrupted development may increase vulnerability to mental illness, substance abuse

June 02, 2022
UC Irvine pediatric neurologist Tallie Z. Baram, MD, PhD
By understanding parental unpredictability in sequences and patterns of care, "we may be able to mitigate this early-life adversity through teaching parents, caregivers and others preventative or interventional behavioral approaches,” says Dr. Tallie Z. Baram, a UCI distinguished professor. Photo by Steve Zylius / UCI

Irvine, Calif. — Researchers at the University of California, Irvine are conducting pioneering research into the concept that unpredictable parental behaviors, together with unpredictable environment, such as lack of routines and frequent disasters, disrupt optimal emotional brain circuit development in children, increasing their vulnerability to mental illness and substance abuse.

In an article published online today in Science, pediatric neurologist Tallie Z. Baram, MD, PhD, corresponding author and UCI distinguished professor in the Departments of Anatomy & Neurobiology, Pediatrics, Neurology and Physiology & Biophysics; and Matthew T. Birnie, first author, a UCI postdoctoral researcher, describe the principles of emotional brain circuit formation gleaned from animal studies, and their impact on children’s cognitive development and mental health.

"Existing measures of early-life adversity explain only some of the variance in the cognitive and mental health outcomes of children," said Baram. "When we include unpredictability in sequences and patterns of care, we explain a lot more. This novel concept has been pioneered by UCI and is supported by our studies of children and mice and now by research in other places in the world."

Baram said this perspective starts with basic principles of how the brain’s sensory — audio and visual — and motor circuits are established and refined, and applying those to emotional circuits that govern reward-, stress- and fear-related behaviors.

"It’s not only positive or negative parental signals, but also the patterns of these behaviors and especially their predictability or unpredictability, that are linked to adverse outcomes such as poor emotional control in later life," she said. "The latter are indicators of higher risks for mental illness, post-traumatic stress disorder and substance abuse.”

The formation of sensory brain circuits involves an initial phase of genetically and molecularly driven actions, including neuronal migration and the establishment of synapses. Complex emotional and cognitive human behavior involves many decisions and actions and are also executed by brain circuits. These higher-order circuits include the interactions of the prefrontal cortical areas, thalamic nuclei, hippocampus, amygdala and hypothalamic nuclei, and subcortical regions of the brain.

They receive numerous streams of information that promote activity of the neurons in the circuits. This activity is required for maturation of the components and refinement of the integrative connections. In early life, as these emotional circuits are developing, parents are the proximate primary environment: They are the source of information that influences the child’s brain maturation.

Studies of mice reared by dams displaying unpredictable behavior sequences (but the same total amount of care) during the early postnatal period show that maternal behaviors influence synaptic connectivity in key brain nodes, including those that contribute to stress. Research involving infants and children suggests that unpredictable patterns of maternal behaviors are associated with later deficits in emotional control and behaviors. These effects persist even after correction for other early-life variables such as maternal sensitivity to the infant’s needs, socioeconomic status and maternal depressive symptoms.

“What’s significant about this research is that it identifies new targets for intervention and helps us think of measures we can put in place to best support the development of mentally and cognitively healthy children,” Baram said. “Unpredictability is actionable, because we can aim to inform and educate parents, caregivers and others about the importance of predictable signals and environments to infants’ and children’s brain maturation.”

Baram and her team are continuing to build on their research at the UCI Conte Center. “We are conducting mechanistic studies in experimental rodents and monitoring infants, children and adolescents in the center. We are now ready to test our discoveries in large scale, ‘real-world’ research,” she said.

This research was supported by the National Institutes of Health under grants P50 MH096889, MH73136, and NS108296; the Donald L. Bren Foundation; and the Hewitt Foundation for Biomedical Research. 

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