Sex and gender 2: Brain structure

Question 1

What is brain macrostructure?

Answer 1

Large-scale measures, overall structure
Brain size
Gyrification - organisation, cortical complexity
Cortical maturation - development, structural asymmetries
Structural asymmetries

Question 2

What is brain microstructure?

Answer 2

Small-scale measures, structure of specific brain regions/subcortical structures - gyri, sulci, sub-cortical regions
Size/shape/volume of specific brain regions
GM:WM ratio
Synaptic density

Question 3

What is structural connectivity?

Answer 3

Physical connections between two or more areas - has been investigated using both macrostructural and microstructural measures

Question 4

How does brain size differ with sex/gender? What could a confound of this be?

Answer 4

Peters (1991) on average male brain is larger and heavier than the average female brain
However, link to behaviour unclear and significance of absolute brain size is unclear

Confound - this could be due to differences in body size - epidemiology of height and brain size are quite similar

Question 5

When controlling for body size differences, do males have larger intracranial volume, total brain volume, GM, WM, and CSF absolute volumes than females?

Answer 5

Yes

Question 6

Do females on average have larger volumes and higher tissue densities in the:
left amygdala
hippocampus
insular cortex
putamen
right VI lobe of the cerebellum
left claustrum
parahippocampal gyri
posterior cingulate gyri
precuneus
temporal poles
cerebellum
areas in the left posterior and anterior cingulate gyri
right amygdala?

Answer 6

No, males do

Question 7

Do females have on average higher density in the left frontal pole, and larger volumes in the:
right frontal pole
inferior and middle frontal gyri
pars triangularis
planum temporale/parietal operculum anterior cingulate gyrus
insular cortex
Heschl’s gyrus
bilateral thalami
precuneus
left parahippocampal gyrus
lateral occipital cortex

Answer 7

Yes

Question 8

When Sanchis-Segura et al. (2019) investigated sex/gender diffs in brain size, adjusting for differences in total intracranial volume (TIV) in 5 different ways, how did sex differences change?

Answer 8

• All TIV-adjustment methods reduced the number of sex differences
• But their results were very different from each other - some resulted in women’s brains showing larger volumes, others removed the sex differences altogether.

Question 9

Since different methods of controlling for body size can alter brain measurements so much, what are male-female differences in brain size better conceptualised as? (Sanchis-Segura et al., 2019)

Answer 9

Male–female differences in brain size are better conceptualised as size differences resulting from overall size differences and variation in total intracranial volume as opposed to sex/gender effects per se

Question 10

What is cortical complexity?

Answer 10

More cortical folding - far more sulci thus more tissue in a small space

Question 11

Luders et al. (2004) - did they find greater cortical complexity in men or women?

Answer 11

Women

Possibly “off-sets” differences in brain volume? Compensates for smaller brain volume as they are fitting more into a small space?

Question 12

What is cortical maturation?

Answer 12

How the brain develops and changes over time

Question 13

Ranahan et al. (2010) conducted longitudinal MRI scans to assess cortical maturation - what did they find?

Answer 13

Sex/gender differences in cortical thickness change across adolescence, in spatially heterogenous manner - changed across time
- In frontal regions, such as the anterior cingulate, prefrontal cortex, and orbitofrontal cortex, cortical maturation was slower in men compared to women – could be associated with the female-favouring sex/gender difference for prefrontal-mediated cognition
- Parietal-occipital regions develop faster in men compared to women – could be associated with the male-favouring sex/gender difference for visuospatial tasks

Question 14

What hormone-related differences are there in cortical maturation?

Answer 14

More able they were to use testosterone in the brain - more male typical pattern of brain development regardless of sex

Question 15

What sex/gender differences did Ritchie et al. (2018) find in cortical volume, cortical thickness, and subcortical volume?

Answer 15

Men = greater cortical volume
Women = greater cortical thickness (esp. in parietal lobe)
Men = larger volumes in subcortical regions

Question 16

What was overlap between men and women like for grey matter volume, white matter volume and total brain volume? (Ritchie)

Answer 16

Significant overlap - many ppts not fitting in male curve or female curve
Males shifted to right, indicating higher volume, male curves also wider, indicating greater variance in men

Question 17

What is the role of the planum temporale?

Answer 17

A cortical region known to be involved in language comprehension (near Wernicke’s area)

Question 18

What sex-related structural asymmetries did Kulnych et al., (1994) find for the planum temporale?

Answer 18

• Men showed an asymmetry (larger left PT compared to right), women did not (PT was the same size in both hemispheres)
  
  • Opposite of what you’d expect based on verbal ability difference
  • BUT, this finding has not been consistently replicated

Question 19

Is there likely to be a sex/gender difference in the PT?

Answer 19

Probably not

- Guadelupe et al., (2015) synthesised data from three large MRI data sets (N = 4160), and found a stronger leftward asymmetry in the PT for men compared to women
- In contrast, Sommer et al., (2008) conducted a meta-analysis of 13 studies (n = 807) investigating the PT and find no sex/gender difference in asymmetry…
- Clinical data also support the lack of a sex/gender difference in asymmetry of the PT
- If there was a sex/gender difference in the asymmetry of the PT, we would expect a sex/gender difference in outcomes following a stroke/lesion to this area
- No sex/gender difference in the likelihood of asphasia (Plowman et al., 2012; Watila & Balarabe, 2015) - suggests no difference in asymmetry - left side not bigger or smaller

Question 20

What is grey matter vs white matter?

Answer 20

• GM = outer layer, cell bodies
• WM = axons, myelin, connections

Question 21

How does the GM-WM ratio change with age?

Answer 21

WM growth predominates until early adulthood. After the age of 50, WM volume typically decreases more quickly than GM volume; thus, the GM—WM ratio increases slightly as age increases

Question 22

Is absolute WM volume higher in men or women?

Answer 22

Men (makes sense with regards to brain size)

Question 23

Is absolute GM volume higher in men or women?

Answer 23

Women (after correcting for differences in cranial size)

Question 24

What are higher GM:WM ratios in women than men attributed to?

Answer 24

Mainly due to decreased WM in women
Thus, sex differences are greater in WM than GM

Question 25

How did Joel et al. (2015) ensure that their analysis was not measure, analysis or sample dependent?

Answer 25

Used different analyses and included different imaging types

Question 26

Joel et al. (2015) found that internal consistency in brains was low - what does this mean?

Answer 26

Most individual brains had a mixture of ‘male’ and ‘female’ typical GM volumes in different areas Few areas were found to have high internal consistency in either male or female brains

Question 27

Is it in men or women that there are more neurons in the frontal and temporal cortex, and a higher number of cell bodies in neocortices?

Answer 27

Men

Question 28

What are issues with using post-mortem brain analyses?

Answer 28

Cause of death, age and medication effects interfere

Question 29

In what lobe was neuronal density found to be 11% higher in women compared to men?

Answer 29

Temporal

Question 30

Is it true that Alonso-Nanclares et al. (2007) reported that women showed lower synaptic density in all layers of the temporal neocortex, as compared to men? What are limitations of this study?

Answer 30

Yes Suggested that this may be reflective of a “more complex” network in this region in men. This study was limited both by a small sample size (n = 8) and by the inclusion of epileptic participants, and so this finding might partly reflect synaptic reorganization effects on synaptic density.

Question 31

What is structural connectivity (white matter tracts connecting brain regions) typically measured with?

Answer 31

Diffusion weighted imaging

Question 32

The size or shape of what structure is one of the most frequently cited examples of sex/gender differences in structural connectivity?

Answer 32

Corpus callosum Big white matter structure between two hemispheres - allows lateralisation and asymmetry

Question 33

Are posterior subsections of the corpus callosum (especially the splenium) larger in women or men?

Answer 33

Women In terms of volume and density However, inconsistent findings: Some studies show larger corpus callosum sections in men compared to women Others found no sex/gender differences

Question 34

Controlling for differences in overall brain size, is the whole corpus callosum bigger in men or women?

Answer 34

Women However, Eliot et al. (2021) argued that since most studies on sex/gender differences in the corpus callosum included <100 participants, they are likely underpowered and not able to detect the estimated effect size

Question 35

Do men or women exhibit more intrahemispheric connectivity and interhemispheric connectivity? Ingalhalikar et al., (2014)

Answer 35

Men - exhibited greater intrahemispheric structural connectivity Particularly between the frontal, temporal, and parietal lobes. (between same hemisphere) Women - exhibited greater interhemispheric structural connectivity (more communication between hemispheres)

Question 36

What are limitations of Ingalhalikar et al., (2014) study of intra and interhemispheric connectivity?

Answer 36

- They did not control for brain size, a factor known to both vary according to sex/gender and to influence structural connectivity - Only found sex/gender differences in a small subsample of the 9,000 connections assessed in their study - More analyses run - more likely to find a false positive - Possibly overinterpreted their results (claims regarding the effect of the sex/gender diffs in connectivity on behaviour were made)

Question 37

What does fractional anisotropy measure?

Answer 37

- FA measures the degree of anisotropy (direction) of water molecules in neural tissue. Without obstacles, water molecules diffuse freely in any direction, a pattern that may be changed by the presence of macromolecules, cell membranes, etc. - High anisotropy = good white matter integrity

Question 38

Is FA higher in the corpus callosum of men or women? (Westerhausen et al., 2003)

Answer 38

Men Possibly reflective of thicker myelination and/or less inter-fibre space in the average male corpus callosum.

Question 39

Westerhausen et al. (2011) reported greater FA and lower MD in what subregion of the corpus callosum in men?

Answer 39

Anterior genu subregion Possibly indicative of stronger, more efficient callosal-frontal connectivity in men

Question 40

Is the finding that FA is higher in male corpus callosum consistent?

Answer 40

No Some studies have demonstrated higher FA in the corpus callosum in women compared to men Others suggest there are no sex/gender differences Still further studies have shown that that sex/gender differences in WM microstructure become non-significant after controlling for differences in intracranial volume Overall, there is an on-going debate regarding whether sex/gender differences in the macro-and microanatomy of the corpus callosum truly exist, as well as whether sex/gender differences in WM microstructure exist in the brain globally

Question 41

What should brains be considered as instead of being sexually dimorphic?

Answer 41

Brains should be conceptualized as “mosaics of features”, some of which are more common in women compared to men and vice versa So, there are some small, reliable sex/gender differences at population level – and these are important – but brains are not sexually dimorphic