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Sex differences in brain connectivity and male vulnerability in very preterm children
Nataliia Kozhemiako1, Adonay S Nunes1, Vasily A Vakorin1,2,3
1Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada.
Insights
Very preterm boys show greater disruptions in brain network communication compared to girls, suggesting a potential cause for higher male vulnerability. This difference in neurophysiology may impact long-term cognitive and behavioral outcomes.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Pediatric Neurology
Background:
- Females born very preterm (≤32 weeks gestation) exhibit better cognitive and behavioral outcomes than males.
- The underlying neurophysiological mechanisms for this observed sex difference in brain resiliency remain unclear.
- This study investigates potential sex-based differences in brain connectivity alterations in very preterm infants.
Purpose of the Study:
- To test the hypothesis that very preterm males exhibit more significant functional connectivity alterations than females.
- To explore the relationship between brain connectivity deviations, psychometric scores, and neonatal factors in very preterm children.
- To identify sex-specific neurophysiological differences in brain network communication following very preterm birth.
Main Methods:
- Resting-state magnetoencephalography (MEG) recordings were obtained from 100 children at age 8 years.
- Participants included very preterm boys and girls, and full-term control groups (boys and girls).
- Neuromagnetic source dynamics were analyzed to estimate inter-regional phase-synchronization for functional connectivity.
Main Results:
- Very preterm boys showed significantly greater deviations in functional connectivity compared to same-sex full-term controls than very preterm girls did.
- Significant differences in brain connectivity were found between very preterm and full-term boys, but not between very preterm and full-term girls.
- Sex differences in functional connectivity were evident in the very preterm group but not in the full-term group.
Conclusions:
- Very preterm boys experience more pronounced alterations in resting-state brain network communication than very preterm girls.
- These sex-specific connectivity disruptions in very preterm boys may underlie their increased vulnerability to long-term cognitive and behavioral challenges.
- Understanding these neurophysiological differences is crucial for developing targeted interventions for preterm infants.
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.
