Running head: SEX DIFFERENCES IN THE HUMAN BRAIN

Biological Sex Differences in the Human Brain:

Understanding Current Literature
Lorraine G. deDanann
Salt Lake Community College

SEX DIFFERENCES IN THE HUMAN BRAIN

Biological Sex Differences in the Human Brain:
Understanding Current Literature
Are the brains of males and females biologically different? Is it possible to map the
differences using Magnetic Resonance Imaging (MRI) scans, or to measure the differences using
cognitive testing methods? And if we are able to measure differences, do those differences vary
depending on age or hormone level? For years, researchers and scientists believed that the
differences between male and female brains were not distinct enough to warrant further research.
For this paper, we define male and female by biological sex, referring to the biological status of
an individual, usually categorized as male, female, or intersex. In his papers on the subject,
Cahill explains that neuroscientists have tested their theories almost exclusively on male rats,
because they did not want to deal with the complications from female hormones. Neuroscience,
he explains, has long believed that sex differences in the brain are not fundamental (Cahill, 2012;
2014). This review will follow the current literature on brain research with regards to biological
sex, to better understand the trends and current direction of the research.
In a paper from Gong, He, and Evans (2011), the authors summarize twenty years of
findings related to brain connectivity research with regards to biological sex. They pulled
research from studies that used Positron Emission Tomography (PET) and MRI data. The PET
scans showed that males have a greater functional connectivity in the right amygdala, and
females have a higher functional connectivity in the left amygdala. These results are supported
by a 2006 study by Kilpatrick, Zald, Pardo, and Cahill (as cited by Cahill), and the meta-analysis
by Ruigrok et al (2014). Gong et al. (2011) also found a pattern similar to other studies, in that
the differences largely manifest after the age of 13. They conclude that there is enough evidence
of substantial difference in brain connectivity related to biological sex to warrant further

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research, and that it should be "mandatory to take gender into account" when considering the
parameters of future studies (Gong et al., 2011).
The meta-analysis from Ruigrok, et al. (2014) looked at 126 articles from studies that
included mean brain volumes for human males and females, intracranial volume, total brain
volume, cerebrum, grey matter, white matter, cerebrospinal fluid, or cerebellum. The goal of the
meta-analysis was to discover if differences in measurement of the brain can be found related to
biological sex; specifically, if the brains of males and females differ, and if they do, in what ways
they differ. They found that males had larger (absolute) volumes than females in the grey matter
(9.4%), white matter (12.9%), cerebrum (9.8%), cerebellum (8.6%), and intracranial space
(12%). Males have a larger gray matter volume in the hippocampi, anterior parahippocampal
gyri, and areas in the left posterior and anterior cingulate gyri. Females have a larger volume in
the left parahippocampal gyrus and lateral occipital cortex, insular cortex, anterior cingulate
gyrus, and parietal operculum. The study had some limitations. The studies looked at the
absolute volumes - meaning, brain volumes that were not adjusted for body weight or height.
Also, the mature age range, which comprised the bulk of the brain scans, spans 42 years, and
could not be distinctly broken down for more meaningful data (Ruigrok, et al., 2014).
The study by Ingalhalikar et al. (2014) sought to understand the underlying reasons why
the human brain shows differences based on biological sex; why males have better motor and
spatial abilities, and females have better memory and social cognition skills. They discovered
that the differences were much more pronounced in adolescents between 14 and 17 years old
than in children younger than 13 years old, suggesting that the differences develop during
adolescence; that they are developmental in nature. They looked at the connectomes in the brain
to find patterns (this is in contrast to many of the other studies, which look at MRI or PET scans

SEX DIFFERENCES IN THE HUMAN BRAIN

for their data comparisons). Connectomes are the neural networks, tens of billions of neurons
connected through trillions of synapses, which provide the network of connections within the
brain. This study used tests to measure the structural connectivity between neural networks, to
discover if differences appear that are related to biological sex. Ingalhalikar et al. found that
females display greater connectivity in the supratentorial region, which contains the cerebrum.
Males show greater connectivity within each hemisphere. The authors explain that their test
results reveal fundamental sex differences in the structural architecture of the human brain
(Ingalhalikar et al., 2014).
The study by Satterthwaite et al. (2014) took past information about sex differences in the
brain - starting with previous studies that showed differences in white and gray matter volumes
between males and females - and sought to understand if the measured differences in brain
structure translates into differences in functional brain networks. The study included 722
participants between 8 and 22 years old, which were stratified based on their age and sex. They
tested using a number of cognitive testing methods, including tests designed to measure memory,
learning, reasoning, identification, motor skills, and memory recall. The authors of the study
stratified the participants by age, to see if the differences shown would be more or less
prominent. They found that males scored higher on spatial and motor tasks, and were more
accurate on language functioning. Females were faster on nonverbal reasoning and emotion
identification. The authors note that the participants who mapped higher on the male pattern of
cognition showed a higher level of male connectivity (if they showed more "male" on the brain
scan, they scored higher in the "male" patterns of cognition). The authors explain that this
suggests a link between sex differences in patterns of cognitive style and connectivity
(Satterthwaite et al., 2014).

SEX DIFFERENCES IN THE HUMAN BRAIN

However, some current studies have found that not all structures of the brain are different
between the sexes. The meta-analysis by Tan, Ma, Vira, Marwha, & Eliot (2016) aimed to
discover if the human hippocampus is genuinely different between males and females;
specifically, if the hippocampus is larger or smaller in either sex. They pulled data from more
than 76 published papers, which in total included samples from more than 6,600 healthy
individuals. Most of the studies used mapped the size of the left and right hippocampi separately,
and some of the studies showed the size of the bilateral (total) hippocampal volume (HCV). They
found that, while males show a larger HCV than females, when adjusting for individual
differences in the total brain volume (TBV) and intracranial volume (ICV), results showed no
reliable difference related to sex (Tan et al., 2016). This is in direct contrast from the results from
the Ruigrok et al. study, which found larger gray matter volume in the hippocampi in males;
however, their study did not adjust for TBV or ICV, which may explain the seemingly
conflicting results (2014).
Other researchers believe that the human brain is not distinctly male or female, but rather,
a map of variability. Joel et al. (2015) make the case that the human mind shows substantial
variability, with most minds landing somewhere on the continuum spectrum between male and
female. They assessed 281 individuals using voxel-based morphometry, and compared this to
data from two other studies. They found that 24-52% of the individuals showed substantial
variability, while only 2.5%-10.5% of the brains were internally consistent (showing mostly
male or mostly female traits). The other individuals were mapped somewhere in the continuum
spectrum. The authors argue that their findings do not support the view that brains can be
mapped according to sex/gender, as they found more substantial variability than internal
consistency in all samples. They suggest that while there are sex/gender differences in brain

SEX DIFFERENCES IN THE HUMAN BRAIN

structure, human brains do not fall clearly into "male" or "female - instead, the human brain is
like a mosaic, with some features more common in males, and other features more common in
females. However, the authors of the study found that some of the study participants were
mapped more clearly into the extremes of the continuum more clearly into the male or
female zones, suggesting that, while variability exists, trends based on biological sex could be
seen in the data (Joel et al., 2015).
A few studies have tried to understand the relationship between brain differences
correlated to biological sex and hormone levels; one specific method of studying these
relationships is to study people who have altered hormones. A review from Kreukels and
Guillamon (2016) sought to understand if the brain differences between men and women were
paralleled in the data from transgender individuals - specifically, in trans women (male to female
transgender), and in trans men (female to male transgender). If the differences are biological,
how would those with gender incongruence appear? The authors wondered if sex hormone levels
could affect both brain structure and function (Kreukels & Guillamon, 2016). In male to female
transgender individuals undergoing hormone treatment that included estrogen and anti-androgen
medications, the total brain volume decreased, suggesting that female hormones may cause a
reduction in total brain volume. The female to male transgender individuals undergoing
testosterone treatment showed an increase in total brain and hypothalamus volumes, and
increases in cortical thickness (Kreukels & Guillamon, 2016). This suggests that hormones play
a key role in the biological differences in the human brain.
Conclusion
Studies about biological sex differences in the brain are ongoing, and a number of
questions remain unanswered. But current literature suggests that differences related to

SEX DIFFERENCES IN THE HUMAN BRAIN

biological sex do exist, and that they can play a crucial role in understanding how chromosomes
and hormones related to sex have an effect on the human brain. Multiple studies have found that
females have a higher functional connectivity in the left amygdala, which is believed to be
involved in the processing of conscious emotion. Males have been shown to have a greater
functional connectivity in the right amygdala, which plays a role in the nonconscious processing
of emotion such as fear. This suggests that males and females react differently to stimuli, and to
different situations.
Some answers are not yet clear, and different studies have produced different results. The
meta-analysis by Tan et al. (2016) found that while other studies have shown a larger
hippocampal volume in males, when adjustments are made in the total and intracranial brain
volume to account for the difference in weight and height of the individual, the results showed
no difference related to sex. The meta-analysis by Ruigrok et al. (2014) showed a difference in
the hippocampal volume between males and females, but the authors discussed the probable
limitations of their study, in that the absolute brain volumes were not adjusted for body weight or
height. More research is needed to confirm or dispute these differences.
The studies by Ingalhalikar et al. (2014) and Satterthwaite et al. (2014) found that the
differences in the brains of human males and females are more pronounced after the age of 13,
particularly during the adolescent period between the ages of 14 and 17. This suggests that the
hormonal changes that occur during adolescence may have a direct effect on the brain.
Satterthwaite et al. (2014) also found a correlation between the masculine or feminine cognitive
style of the individual and the degree to which their brains correlated to male or female patterns.
Joel et al. (2015) posit that the differences in the human brain related to biological sex are too
variable, and that the human brain is not distinctly male or female, but instead falls somewhere

SEX DIFFERENCES IN THE HUMAN BRAIN

on a continuum. However, they found that those who mapped at either extreme of the continuum
- those who were more distinctly male or female were more likely to show traits that have been
previously attributed to their biological sex from other studies (Joel et al., 2015).
But what can account for these differences? A number of theories exist. Some believe
that environmental factors may play a role, or that the experiences of an individual may
effectively change their brain. Another theory is that changes during pregnancy to the embryo
related to androgens cause differences in the brains of males and females, or that these are
caused by hormonal changes during adolescence and puberty. The Kreukels and Guillamon
(2016) study found a correlation between hormone levels and the brain when comparing data
from transgender and cisgender participants; their study showed a correlation between taking
testosterone and an increase in total brain volume, and another correlation between those taking
estrogen and anti-androgen medications and a decrease in total brain volume. More research is
needed to better understand the correlation between hormones and the human brain.
A large amount of data has emerged suggesting that male and female brains are indeed
biologically different - different enough to warrant further research in the area, and to demand
that experiments include both male and female test subjects. Further research is needed to
understand the biological differences that exist, as well as to better explore what causes these
differences, and what implications they may have in psychology, medicine, education, and our
society as a whole.

SEX DIFFERENCES IN THE HUMAN BRAIN

References
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