Lecture 7 - Sex/Gender Differences in Brain Structure

Question 1

sex/gender influences on brain structure

Answer 1

• sex/gender differences have been found in brain structure across multiple levels of analysis
• macrostructure (large scale measures, overall structure)
  > brain size
  > gyrification
  > cortical maturation
  > structural asymmetries
• microstructure (small scale of specific brain regions)
  > size/shape/vol of regions
  > GM/WM ratio
  > synaptic density
• structural connectivity - used both micro and macro structural measures. literal connections between two areas in the brain

Question 2

macro structure - sex/gender differences in brain size

Answer 2

• Peters (1991) - m brain larger and heavier than f brain. link to behaviour is unclear. due to difs in body size?
• Ruigrok et al. (2014) - meta analysis of post mortem and imaging studies. m larger ICV TBV, CB, GM, WM & CSF & bigger cerebellum vol.
  > m larger vol & tissue density in: l amyg, hipp, insular cortex, putamen.
  > f higher density in left frontal pole and larger vol in right frontal pole, inferior and middle frontal gyri
• signif but not strong signif in sex differences with overall being .50.
• could be false positive & depend on analysis method & specific method by which sex/gender difs in the body are controlled
• sanchis-segura et al. (2019) - sex/gender difs in brain size adjusting for TIV in 5 ways. all adjustments reduced the no. sex difs but results were very different from each other - some results showed womens brain larger vol, others removed difs
  > sex difs are better conceptualised as size differences resulting from variation in total intracranial vol opposed to sex/gender effects

Question 3

macro structure: sex/gender differences in cortical complexity

Answer 3

• greater cortical complexity = more ‘folding’ so more brain tissue compacted into an area.
• Luders et al. (2004) - f greater cortical complexity scores than men. may ‘offset; difs in brain vol.
  > also looked at cortical complexity of different lobes - signif difs favouring women were espec R inferior frontal and R parietal lobe.

Question 4

macro structure: sex/gender differences in cortical maturation

Answer 4

• Raznahan et al. (2010) looked at changes in adolescence (most change).
  > cortical thickness change across adolescence
  > in frontal regions, cortical maturation slower in men vs women.
  > parietal-occipital regions develop faster in men vs women
  > some hormone related effects with specific androgen receptor genes presence. more testosterone resulting in more male typical patterns of development.

Question 5

macro structure: structural sex/gender differences throughout the brain

Answer 5

• Ritchie et al. (2018) - conducted the largest single-sample neuroimaging study of sex/gender differences in brain:
  > 44-77 y/o neuroimaging
  > m greater cortical volume
  > f greater cortical thickness (espec parietal)
  > m larger vol in subcortical regions
  > m more GM, WM and TBV
  > m also greater variance within them

Question 6

macro structure: sex/gender differences in structural asymmetries

Answer 6

• L hem typically dominant for language
• R hem = visuospatial
• asymmetries can also be structural
• women tend to be better with verbal tasks and men with spatial tasks
• planum temporale (language comp): m showed asymmetry (L larger than R) while women did not.
• Guadelupe et al (2015) - found stronger leftward asymmetry in PT for men vs women
• Somner et al (2008) in contrast found no gender difs in asymmetry
• no sex/gender dif in likelihood of aphasia (Plowman et al. 2012)

Question 7

micro structures: structural sex/gender differences throughout the brain

Answer 7

• Ritchie et al. (2018)
  > m had greater cortical volume (espec ofc, insula, cingulate gyrus). f greater cortical thickness espec parietal lobe
  > m larger vol in subcortical areas inc amygdala & hippocampus
• may be due to m brain being bigger?
• findings overlapped

Question 8

micro structure: sex/gender differences in grey/white matter

Answer 8

• assessed looking at absolute volumes, or ratio
• absolute WM higher in men. BUT absolute GM higher in women
• allen et al. (2003) - women higher GM:WM ratio across all structures. sex/gender effect greater on WM than GM - the higher ratios in women were due to reduced WM in women vs men
• Van der linden et al (2017) - women higher ratio throughout cortex even after controlling for difs in body size.
• Joel et al. (2015) - the human brain mosaic - examined difs in gm, wm, connectivity using dif imaging types & analyses to focus on internal consistency (how homogenous brains are)
  > largest sex/gender difs were left hipp and left caudate
  > low internal consistency & most brains had a mixture of m and f features

Question 9

micro structure: sex/gender differences in synaptic and neuronal density

Answer 9

• stark et al (2007) - higher no. neurons in frontal and temporal cortex in men vs women & higher no. cell bodies in m neocortices
• but post mortem studies cannot consider age & medication effects
• witelson et al. (1995) - neuronal density was 11% higher in women vs men in temporal lobe - may exp some observed gender/sex difs in cognition
• alonso-nanclares et al (2007) - f show lower synaptic density in all layers of temporal neocortex - may reflect more complex network in this region in m (but small sample)

Question 10

sex/gender differences in structural connectivity

Answer 10

• refers to WM tracts connecting regions
  > macrostructural measures: connection-wise analysis, estimates of size/vol of wm tracts, looking at specific connections
  > microstructural measures: fractional anisotropy & mean diffusivity of wm tracts, looking at integrity and direction of tissue

Question 11

structural connectivity: macrostructural measures

Answer 11

• size and/or shape of CC
• posterior subsections of CC are larger in women vs men
  > splenium seems to be larger in volume and density in f
  > posterior midbody
  >isthmus
• some studies show larger CC sections in men vs women others show no differences
• Ardekani et al. (2013) - found whole CC was larger in women vs men
• Eliot et al (2021) - since most studies less than 100 pp’s they are likely underpowered and not able to find effect size.
• Ingalhalikar et al (2014) - men greater intrahemispheric structural connectivity vs women especially between frontal, temporal and parietal lobes. women greater INTERhemispheric structural connectivity across both hems.
• larger brains usually show more intrahemispheric connectivity (more m) while smaller showed greater interhemispheric connectivity (more likely to be f)
• methodological limitations in ingalhalikar: did not control for brain size, only found difs in small subsample, overinterpreted results
• Tunc et al (2016)
  > m greater connectivity in motor, sensory and ef networks
  > f greater connectivity within memory, attention and social cognition networks.
  > f more inter hemispheric connectivity while men more intra hemispheric connectivity

Question 12

structural connectivity: microstructural measures

Answer 12

• typically report measures of.. as indices of WM fibre organisation & integrity:
  > fractional anisotropy (FA) - measures degree of anisotropy of water molecules in neural tissue. without obstacles water molecules diffuse freely which may be changed by macromolecule presence or cell membranes etc. diffusion is isotonic here only along the tube (axon) and allows to infer alterations in the axonal diameter, fiber density or myelin structure (high FA = good WM integrity)
  > mean diffusivity (MD) - measures directions of diffusion of molecules within brain. inc MD is consistent with inc water content & less resistance so higher diffusion rates. (higher MD = poor WM integrity)
• westerhausen et al. (2003) - higher FA in CC in men vs f (despite CC being seen as bigger in f). reflect thicker myelination & less inter fibre space in m cc
• westerhausen et al. (2011) - greater FA and lower MD in anterior genu subregion of cc in m. indicate stronger callosal-frontal connectivity in m.
• results inconsistent. some suggest higher FA in cc in women. others suggest no differences.

Question 13

the human brain mosaic

Answer 13

• there is overlap between m and f brain.
• should shift from concept of sexually dimorphic brain. instead, conceptualised as mosaics of features some of which are more common in women vs men
• so there are some small sex/gender difs at pop level but brains not sexually dimorphic