Geschlechtsunterschiede in der funktionellen Konnektivität während der Entwicklung des fetalen Gehirns

Eine interessante Studie hat die Gehirne des Fötus im Mutterleib auf Geschlechterunterschiede untersucht:

Highlights

  • Limited research has assessed sex-related differences in fetal brain connectivity.
  • Functional connectivity (FC) data were collected from 118 human fetuses.
  • 16 distinct fetal FC networks were identified using a community detection algorithm.
  • Sex-related changes in fetal FC were examined using enrichment analysis.
  • We confirm for the first time that network FC differs with sex in utero.

ABSTRACT

Sex-related differences in brain and behavior are apparent across the life course, but the exact set of processes that guide their emergence in utero remains a topic of vigorous scientific inquiry. Here, we evaluate sex and gestational age (GA)-related change in functional connectivity (FC) within and between brain wide networks. Using resting-state functional magnetic resonance imaging we examined FC in 118 human fetuses between 25.9 and 39.6 weeks GA (70 male; 48 female). Infomap was applied to the functional connectome to identify discrete prenatal brain networks in utero. A consensus procedure produced an optimal model comprised of 16 distinct fetal neural networks distributed throughout the cortex and subcortical regions. We used enrichment analyses to assess network-level clustering of strong FC-GA correlations separately in each sex group, and to identify network pairs exhibiting distinct patterns of GA-related change in FC between males and females. We discovered both within and between network FC-GA associations that varied with sex. Specifically, associations between GA and posterior cingulate-temporal pole and fronto-cerebellar FC were observed in females only, whereas the association between GA and increased intracerebellar FC was stronger in males. These observations confirm that sexual dimorphism in functional brain systems emerges during human gestation.

Quelle: Sex differences in functional connectivity during fetal brain development

Die Forschung lässt immer weniger Raum für soziale Erklärungen. Jetzt müsste die Sozialisierung der Geschlechter schon im Mutterleib selbst, vor der Geburt, stattfinden, damit sie diese Ergebnisse erklärt. Auf Twitter wurde dazu schon gescherzt, dass die Mutter ja ab der 12 Woche erfährt, welches Geschlecht das Kind hat und sich dann natürlich ganz anders verhält, je nach dem ob es ein Junge oder ein Mädchen ist. Irgendein Gender Studies Mensch wird das auch tatsächlich anführen und geradezu als Beweis für die Stärke der sozialen Kräfte anführen. Überzeugender wird es dabei, gerade wenn man die Wirkung pränataler Hormone in sonstigen Studien sieht, nicht.

Interessant ist auch die Geschichte der Forschung dazu in der Einleitung:

Healthy brain development in utero is imperative for achieving optimal long-term neurobehavioral outcomes. Processes that interfere with normative prenatal development, such as toxin exposure, injury, and infection, can have dramatic consequences (Adams Waldorf & McAdams, 2013; Lanphear et al., 2005; Slopen et al., 2015), and current evidence suggests that it is by acting on formation of brain circuitry in utero that these exposures exert their pernicious effects (Thompson et al., 2009). Furthermore, developmental disorders are increasingly conceptualized as disorders of the brain’s functional and structural connectome and it has been suggested that a better understanding of neurodevelopmental processes in the womb may bring us closer to understanding the developmental origins of disease (Buss et al., 2017; Di Martino et al., 2014). However, current models of healthy gestational brain development lack sex-specific effects. Though sex-related variation in hormone levels are detectable by the 8th week of gestation (Hines, 2010), in utero sexual dimorphism in the development of functional brain networks has yet to be described.

Elegant work spanning decades has born considerable insight into the timing and order within which structures of the brain mature (Huang & Vasung, 2014; Kostovic & Jovanov-Milosevic, 2006). In recent years, however, methodological advances have led to a surge in studies attempting to map development of human functional brain systems before birth using resting-state functional connectivity (FC) MRI (Anderson & Thomason, 2013; M. I. van den Heuvel & Thomason, 2016). Studies that have assessed FC in human preterm or fetal brain development have described overall network properties and have characterized changes in functional connectivity associated with advancing post-conceptual age. These studies have demonstrated that during early brain development: i) cross-hemispheric, cortico-subcortical, and long-range connectivity increase, ii) connections develop in a medial to lateral gradient, and iii) efficiency and modularity increase (Doria et al., 2010; Fan et al., 2011; Fransson et al., 2011; Gao et al., 2015a,b; Gao et al., 2011; Grayson & Fair, 2017; Huang et al., 2015; Smyser et al., 2016; Smyser et al., 2011; Thomason et al., 2014; Thomason et al., 2013; Thomason et al., 2015; M. P. van den Heuvel et al., 2015). However, sex-related variations in functional network formation in utero have yet to be elucidated.

Sexual dimorphism in brain structure and functional connectivity are robustly reported findings across the lifespan (Caviness et al., 1996; Koolschijn & Crone, 2013; Lenroot et al., 2007; Ruigrok et al., 2014; Satterthwaite et al., 2015; Tiemeier et al., 2010). However, limited research has assessed sexual dimorphism in the brain before birth. One prior study assessing sexual dimorphism in utero did not observe any brain volumetric differences between 20-32 weeks (Scott et al., 2011). However, ultrasound studies demonstrate that males have a larger head circumference than females as early as the 2nd trimester (i.e. 14-27 weeks) (Broere-Brown et al., 2016; Melamed et al., 2013). Further, studies in newborns and infants have shown that males and females vary in brain volume and cortical thickness (Choe et al., 2013; Gilmore et al., 2007; Knickmeyer et al., 2014), implicating a likely emergence of sexual-dimorphism in the brain before birth. Gao and colleagues assessed brain functional connectivity development at birth, at age 1 year, and age 2 years and observed greater age dependent increase in frontoparietal connectivity in males than females (Gao et al., 2015b). No other differences in network connectivity were observed between males and females. Similarly, Deoni and colleagues observed no differences in developmental trajectories for cortical growth or myelination of brain regions between male and female brains between the ages of 1 to 6 years (Deoni et al., 2015). Taken together, changes in hormone levels early in gestation, followed by differences in head circumference observed in utero, and differences in brain structure apparent at birth point towards sex differences in the development of fetal functional brain connectivity. However, differences in brain connectivity between male and female fetuses in utero have not been previously described.

Auch eine schöne Ansammlung von Studien, die deutlich machen, dass die Forschung auf dem Gebiet einiges an Fakten aufzuweisen hat.

Aus den Ergebnissen als Bild:

Geschlechterunterschiede Gehirn Fetus

Geschlechterunterschiede Gehirn Fetus

 

Aus der Diskussion:

In the present study, males demonstrated greater FC-GA associations within the CB and between dorsal and ventral regions of the PFC (i.e. PFC – R SFG) than females. While this association was stronger in males, females also demonstrated a similar pattern of FC-GA associations within the CB. Within the CB, as GA increased, intra-cerebellar FC increased, suggesting strengthening of functional connections within the cerebellum is crucial for typical brain development across gestation. The CB experiences the largest growth of any brain region following birth (Choe et al., 2013; Holland et al., 2014), and studies consistently report that males have larger cerebellum grey matter volume than females spanning from childhood to adulthood (Koolschijn & Crone, 2013; Ruigrok et al., 2014; Tiemeier et al., 2010). Taken together, the present findings suggest that greater cerebellar volume in males is mirrored by greater FC integration within the CB network in males than females during gestation. In contrast, FC within the ventral (PFC) and dorsal (R SFG) decreased as GA increased. Both groups demonstrated this FC-GA relationship within the PFC, though it was more pronounced in male fetuses. While some research would suggest that connectivity between dorsal and ventral PFC should grow stronger with age, ultimately leading to the formation of the anterior portion of the default mode network (Power et al., 2011), other research suggests distinct functionality exists in dorsal and anterior prefrontal and cingulate cortex (Bush & Posner, 2000). Perhaps these GA related changes in FC between dorsal and ventral PFC will come to support cogntive and affective processes during later development (Bush & Posner, 2000).

(…)

As expected, the present results suggest that increasing GA is associated with widespread change in FC across the brain. A notable number of FC changes were observed involving SFG, PCC, and visual cortex connectivity with other cortical and subcortical networks. While prior research demonstrated an increase in cross-hemispheric connectivity with increasing age (Smyser et al., 2016), we did not observe a pattern of increasing cross-hemispheric connectivity in the present study. In contrast, many of the connections which changed with increasing GA appeared to be long distance anterior-posterior connections. In interpreting these differences, it is important to note that fetuses in the present study were less than 40 weeks GA, while prior work (Smyser et al., 2016) included term born infants (> 40 weeks GA). The present study suggests that bilateral homotopic connectivity does not begin to mature until the final weeks of gestation (i.e. after 38 weeks) or even until after birth.

Unser Verständnis der Vorgänge der Geschlechterausbildung wird immer besser. Es wäre gut, wenn man diese Forschung dann auch hinreichend zur Kenntnis nimmt. Natürlich ist es nach wie vor schwer bestimmte Verhaltens- und Interessensunterschiede diesen Gehirnunterschieden zuzuordnen. Aber zumindest macht es die Zuordnung zu rein sozialen Erklärungen im Zusammenspiel mit den anderen Studien unwahrscheinlicher