Sex differences in brain connectivity and male vulnerability in very preterm children

Abstract

Evidence indicates better cognitive and behavioral outcomes for females born very preterm (≤32 weeks gestation) compared to males, but the neurophysiology underlying this apparent resiliency of the female brain remains poorly understood. Here we test the hypothesis that very preterm males express more pronounced connectivity alterations as a reflection of higher male vulnerability. Resting state MEG recordings, neonatal and psychometric data were collected from 100 children at age 8 years:very preterm boys (n = 27), very preterm girls (n = 34), full-term boys (n = 15) and full-term girls (n = 24). Neuromagnetic source dynamics were reconstructed from 76 cortical brain regions. Functional connectivity was estimated using inter-regional phase-synchronization. We performed a series of multivariate analyses to test for differences across groups as well as to explore relationships between deviations in functional connectivity and psychometric scores and neonatal factors for very preterm children. Very preterm boys displayed significantly higher (p < .001) absolute deviation from average connectivity of same-sex full-term group, compared to very preterm girls versus full-term girls. In the connectivity comparison between very preterm and full-term groups separately for boys and girls, significant group differences (p < .05) were observed for boys, but not girls. Sex differences in connectivity (p < .01) were observed in very preterm children but not in full-term groups. Our findings indicate that very preterm boys have greater alterations in resting neurophysiological network communication than girls. Such uneven brain communication disruption in very preterm boys and girls suggests that stronger connectivity alterations might contribute to male vulnerability in long-term behavioral and cognitive outcome.K E Y W O R D S neuromagnetic brain connectivity, sex differences, very preterm children Ruth E. Grunau and Sam M. Doesburg are co-senior authors.

Personal perspectives: Infant pain—A multidisciplinary journey

“…The thalamus is a relay hub for sensory input from the periphery to the cortex; therefore, this brain region is of particular interest in understanding long‐term effects of early pain. At age 7‐8 years, we found that greater exposure to neonatal pain (especially in children born 24‐28 weeks GA) was associated with altered MEG oscillatory activity 39 , 40 , 41 , 42 which is generated in the thalamus and reflects functional thalamocortical connectivity. Recently, we established that structural thalamic growth on MRI from early life to term equivalent age is affected by greater exposure to neonatal pain, in two new independent cohorts in Vancouver and Switzerland that underwent serial MRI in the neonatal period.…”

“…Above and beyond neonatal clinical factors related to prematurity, Brummelte and Zwicker as post‐docs, found neonatal pain/stress was related to white matter and grey matter 34 and corticospinal tract maturation 35 in the neonatal period. In a separate cohort, Doesburg and Ranger post‐docs and Vinall a PhD student showed neonatal pain/stress predicted white matter maturity, 36 cortical thickness, 37 regional cerebellar volumes, 38 and neuronal activity 39‐42 at school age, and in turn, cognitive function and behavior. Recently, Doesburg with his students has extended this work 40,42 .…”

“…In a separate cohort, Doesburg and Ranger post‐docs and Vinall a PhD student showed neonatal pain/stress predicted white matter maturity, 36 cortical thickness, 37 regional cerebellar volumes, 38 and neuronal activity 39‐42 at school age, and in turn, cognitive function and behavior. Recently, Doesburg with his students has extended this work 40,42 . Importantly, these changes to brain structure and function were above and beyond relationships with known clinical risk factors related to prematurity.…”

“…Recently, Doesburg with his students has extended this work. 40 , 42 Importantly, these changes to brain structure and function were above and beyond relationships with known clinical risk factors related to prematurity.…”

Developmental Differences in Neuromagnetic Cortical Activation and Phase Synchrony Elicited by Scenes with Faces during Movie Watching

“…For these two participants, we selected the best matched MRI from the pool of the other 18 participants based on the mean distance between each Polhemus point and the closest point on the skull surface derived from the segmented T1 image using the Fieldtrip toolbox ( Oostenveld et al, 2011 ). The same procedure was previously successfully applied in the children cohort of similar age ( Kozhemiako et al, 2019 , 2020 ).…”