Evidence for Developmental Programming of Cerebral Laterality in Humans

Alexander Jones,Clive Osmond,Keith M Godfrey,David I W Phillips,Andrew Whitehouse

doi:10.1371/journal.pone.0017071

Abstract

Adverse fetal environments are associated with depression, reduced cognitive ability and increased stress responsiveness in later life, but underlying mechanisms are unknown. Environmental pressures on the fetus, resulting from variations in placental function and maternal nutrition, health and stress might alter neurodevelopment, promoting the development of some brain regions over others. As asymmetry of cerebral activity, with greater right hemisphere activity, has been associated with psychopathology, we hypothesized that regional specialization during fetal life might be reflected persistently in the relative activity of the cerebral hemispheres. We tested this hypothesis in 140 healthy 8–9 year-old children, using tympanic membrane temperature to assess relative blood flow to the cerebral hemispheres at rest and following psychosocial stress (Trier Social Stress Test for Children). Their birth weight and placental weight had already been measured when their mothers took part in a previous study of pregnancy outcomes. We found that children who had a smaller weight at birth had evidence of greater blood flow to the right hemisphere than to the left hemisphere (r = −.09, P = .29 at rest; r = −.18, P = .04 following stress). This finding was strengthened if the children had a relatively low birth weight for their placental weight (r = −.17, P = .05 at rest; r = −.31, P = .0005 following stress). Our findings suggest that lateralization of cerebral activity is influenced persistently by early developmental experiences, with possible consequences for long-term neurocognitive function.

Highlights

Adverse fetal environments are associated with impaired neurocognitive function in later life, including depression [1], reduced cognitive performance [2] and increased stress responsiveness [3,4,5] but there has been little investigation of underlying processes
Functional magnetic resonance (MR) imaging has shown that the magnitude of HPAA and heart rate responses to stress are better correlated with blood flow in the right hemisphere (RH) than in the left hemisphere (LH) [19]
There were no significant differences in gestational age, birth weight or placental weight between participants and non-participating members of the original cohort

Summary

Introduction

Adverse fetal environments are associated with impaired neurocognitive function in later life, including depression [1], reduced cognitive performance [2] and increased stress responsiveness [3,4,5] but there has been little investigation of underlying processes. At its most gross level, such regional specialization might be seen in the relative activity of the cerebral hemispheres. It is well established that asymmetrical activation of the cerebral hemispheres is associated with altered affective states, including depression [6] and with heightened stress-responsiveness [7]. Damage or dysfunction of the brain is associated with depression if the LH is affected, which promotes a shift towards greater relative RH activity, and with euphoria if the RH is affected, suggesting that functional balance of the hemispheres is important in determining mood [10,11,12,13,14,15,16]. Functional magnetic resonance (MR) imaging (fMRI) has shown that the magnitude of HPAA and heart rate responses to stress are better correlated with blood flow in the RH than in the LH [19]

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