Study identifies sex and gender differences in brain connectivity

Sex, gender and brain connectivity

Research examining possible differences between male and female brains has been wide-ranging, although its findings have not been entirely definitive. A new study has now identified notable brain differences associated with sex, alongside distinct variations associated with a person's gender.

Researchers in the US and Singapore examined fMRI brain-activity scans from 4,757 children aged 9 or 10 who participated in the Adolescent Brain Cognitive Development (ABCD) Study. The group included 2,442 children assigned male at birth (AMAB) and 2,315 assigned female at birth (AFAB).

The team compared these data with the children's responses about their feelings towards their gender, as well as parents' reports of the child's behaviour. These reports included indications of gender dysphoria: a feeling of not being aligned with one's sex assigned at birth.

"Here, we use the term 'sex' to indicate features of an individual's physical anatomy, physiology, genetics, and/or hormones at birth, and we use the term 'gender' to indicate features of an individual's attitude, feelings, and behaviors," writes the team led by neuroscientist Elvisha Dhamala from the Feinstein Institutes for Medical Research in New York.

"Sex is not binary. However, in the ABCD sample analyzed here, all participants reported their sex as either female or male."

Separate patterns in the brain

Using machine-learning algorithms, the researchers found significant sex-related differences in brain connectivity, together with subtler connectivity differences linked to gender. Importantly, the variations associated with sex were distinct from those associated with gender.

This does not show that male and female brains are differently wired from birth. Rather, it suggests that particular activity seen in the scans - within brain networks involved in movement, vision and emotion - can reliably predict whether a brain is male or female.

The indicators associated with gender were less dependable and less clearly defined. They were connected with predictors related to a person's sex, but did not match them, and were distributed more widely across the brain.

"Sex and gender have traditionally been conflated in research when they should have been studied separately," says Dhamala.

The difference reflects the ways in which biology - including genes and hormones - and environment, including social experiences, shape the brain. Since brains are highly adaptable, both internal experiences and the treatment people receive from others can influence gender.

Implications for brain-related illnesses

The findings could carry significant implications. Conditions including ADHD (attention-deficit/hyperactivity disorder) and Parkinson's are more often diagnosed in AMAB individuals, whereas anxiety and Alzheimer's are more commonly diagnosed in AFAB people.

As well as sex, gender may contribute to this imbalance in ways that are more profound than might be expected.

"Women, people AFAB, and sex/gender minorities have historically been excluded from biomedical research. Consequently, this group of individuals is more likely to be underdiagnosed or misdiagnosed for common brain disorders," write the researchers.

"Collectively, these results suggest that sex and gender are both associated with individual functional connectivity and these associations may underlie the sex and gender differences that exist in brain-related illnesses."

Limits of the ABCD Study data

The study's authors highlight an important limitation: the children included have not yet reached puberty, a pivotal period for gender identity and related feelings. The findings could therefore look different among older participants.

Because culture has such a strong influence on gender, additional research will be needed involving a broader range of people, countries and ethnic groups. Until then, studies of the brain may be due for a rethink.

"This research sheds light on the complex and nuanced ways in which biological and environmental factors influence brain organization," Dhamala explains, "and shows the need to consider a person's sex and gender to fully understand health and disease across the human lifespan."

The research has been published in Science Advances.