Nature Neuroscience | Volume 27 | November 2024 | 2253–2260 2254
Resource https://doi.org/10.1038/s41593-024-01741-0
associated brain networks appear to decrease in volume at a faster 
rate than the rest of the brain throughout pregnancy, as determined 
by a subsequent analysis controlling for total GMV (Supplementary 
Tables 1 and 2). GMV reductions were also significantly correlated with 
the participant’s estradiol and progesterone concentrations (Supple-
mentary Table 1). A highly similar pattern of results was observed when 
examining pregnancy-related CT changes (Supplementary Fig. 3 and 
Supplementary Tables 4 and 5). Significant reductions in cortical GMV 
over gestation remained after controlling for standard quality control 
(QC) metrics, albeit with some influence on the magnitude and location 
of the observed effects (Supplementary Figs. 4 and 5).
In contrast, GMV within regions of the default mode (subnetwork 
C), limbic (subnetworks A and B) and visual peripheral networks buck 
the global trend by slightly increasing (for example, temporal poles), 
remaining constant (for example, orbitofrontal cortex) or reducing at 
a much slower rate (for example, extrastriate cortex) than total GMV 
(Fig. 2a,b and Supplementary Tables 1 and 2). CT changes in these 
regions exhibit similar patterns (Supplementary Fig. 3 and Supple -
mentary Tables 4 and 5).
Subcortical GMV changes tied to gestation
Consistent with the broader cortical reductions in GMV, several subcor-
tical regions significantly reduced in volume across gestation (Fig. 3a, 
left). This included bilateral ventral diencephalon (right hemisphere 
values shown in Fig. 3a, right; encompasses hypothalamus, substantia 
nigra, mammillary body, lateral geniculate nucleus and red nucleus 
among others22), caudate, hippocampus and thalamus, along with left 
putamen and brain stem (Supplementary Table 6, q < 0.05).
Next, high-resolution segmentation of the MTL allowed us to 
interrogate subcortical structures at a finer resolution, revealing non-
linear volumetric decreases in CA1 (F(2,15) = 5.84, q = 0.031, R2
adj = 0.36; 
Fig. 3b, left) and CA2/CA3 (F(2,15) = 6.82, q = 0.027, R2
adj = 0.41; Fig. 3b, 
middle) across gestation. PHC exhibited linear volumetric decreases 
across gestation (F(1,16) = 24.87, q < 0.001, R2
adj = 0.58; Fig. 3b, right) 
which was also tied to estradiol (F(1,12) = 20.21, q = 0.005, R2
adj = 0.60). 
All three relationships remained significant after proportional correc-
tion for total GMV. There was no significant change in other subregions 
or total volume of the hippocampal body, or in the parahippocampal 
gyrus (Supplementary Table 7 and Supplementary Fig. 8).
White matter microstructure changes tied to gestation
In contrast to decreasing global GMV, correlational tractography of 
white matter, which tests for linear trends in the data, revealed increas-
ing microstructural integrity across the whole brain during gestation 
(Fig. 4a), concomitant with the rise in 17β-estradiol and progesterone 
(all q < 0.001; Supplementary Fig. 9). Tracts displaying robust corre-
lations with gestational week included the corpus callosum, arcuate 
fasciculus, inferior fronto-occipital fasciculus and inferior longitudinal 
fasciculus (Fig. 4b), as well as the cingulum bundle, middle and superior 
longitudinal fasciculus, corticostriatal, corticospinal and corticopon-
tine tracts (see Supplementary Table 9 for complete list).
Comparing brain changes across pregnancy against controls
We then compared the changes in GMV across gestation to that of typi-
cal variability over time, derived from eight densely-sampled controls23. 
The GMV changes we see across pregnancy far exceed normative brain 
variability (Supplementary Fig. 11). On average, change in cortical GMV 
was nearly three times higher than controls scanned over a similar 
duration (Supplementary Fig. 11a,b). This extends to MTL subfields,