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Some sex differences in brain-connectivity patterns become more pronounced with age, according to new research.
Researchers studying brain-imaging data from people aged between 8 and 100 found that sex differences in the brain’s connections are minimal in early life, but then increase drastically at puberty; some of these differences continue to grow throughout adult life. The study was published as a preprint on bioRxiv1, and has not yet been peer reviewed.
The work could help us to understand why men and women have different likelihoods of developing some mental-health disorders — and perhaps give insight into treating them, say the researchers. For example, women are about twice as likely as men to develop anxiety or depression2, and boys are about four times more likely to be diagnosed with autism spectrum disorder than girls3.
“We are very excited about this study, which to our knowledge is the first one to compare how sex differences in brain networks evolve over the lifespan,” says Amy Kuceyeski, a computational neuroimager at Weill Cornell Medicine in Ithaca, New York.
However, some neuroscientists who spoke to Nature aren’t convinced that the differences found between male and female brains are due to sex, and say the study does not address differences in gender roles, which are known to be important factors when researching brain mechanisms of health and disease.
Human brains do not belong in distinct ‘female’ and ‘male’ categories, says Daphna Joel, a neuroscientist at the University of Tel Aviv in Israel, referring to a 2015 study she co-authored, which suggests that each human brain is a mosaic of features, some of which are more common in men, others in women4.
Sex differences throughout life
In their study, Kuceyeski and her colleagues set out to investigate sex-linked variation in brain development by analysing functional magnetic resonance imaging brain data from 1,286 people, half of whom were male and half female. The scans captured a snapshot of each individual’s brain age, but did not follow the same people throughout their lives. The analysis was based on sex at birth because the researchers didn’t have data on the participants’ gender identities.
They used an artificial-intelligence tool they call Krakencoder to identify sex-linked differences in brain networks. The tool analysed structural connections — physical axonal links between brain regions — and functional connections, which included synchronized brain activity between brain regions.
Their analysis revealed sex-linked differences in both structural and functional pathways in the brain. Functional differences were mainly in higher-order brain networks, which use information from many brain regions to support attention, decision-making and consciousness. Structural differences peaked in midlife and continued to diverge with age, particularly in lower-order networks, which process information gleaned by the senses.
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Throughout life, female participants tended to have stronger functional connections than did male participants between ‘default mode network’ regions, which deal with higher-order processes. And as men got older, their functional connections between the two hemispheres of the cerebellum, used in motor control, grew increasingly strong compared with those of women. Structural connections on each side of the cerebellum also grew stronger in male participants than female participants as they aged.
“One of the most interesting findings is that the timeline of sex differences in brain connectivity aligns with the timeline of sex-hormone levels across the lifespan,” says Yumnah Khan, a cognitive neuroscientist at the University of Cambridge, UK.
She highlights the differences in the default mode network as potentially being linked to mental health. “Females are generally showing stronger functional connectivity,” she says, adding that hyperconnectivity in the default mode network has been linked with depression5.
