Nature Neuroscience | Volume 27 | November 2024 | 2253–2260 2258
Resource https://doi.org/10.1038/s41593-024-01741-0
overlook the full range of changes that unfold within the gestational 
window, and underrepresent the brain’s metamorphosis during preg-
nancy. Furthermore, although observed changes were largely global, 
some regions displayed notable stability (for example, extrastriate cor-
tex). The subcortical region that displayed the strongest relationship 
with gestation week was the ventral diencephalon, which encompasses 
the hypothalamus and subsequent medial preoptic area and paraven-
tricular nucleus—structures critical for inducing maternal behavior12,16. 
The hippocampus exhibited a reduction in volume across gestation, 
and with higher spatial resolution, this reduction was revealed to be 
driven by changes in CA1 and CA2/CA3 subfield volumes, while other 
hippocampal subfields remained stable. Adjacent PHC within the 
MTL also exhibited volume reduction across gestation. While our hip-
pocampal findings are consistent with pre/post studies of pregnancy13, 
the precision lens applied within gestation revealed the nonlinear 
nature of this reduction. Recapitulating and clarifying these region -
ally specific patterns of volume change throughout the MTL merits 
further investigation.
Similar precision imaging studies have captured dynamic brain 
reorganization across other neuroendocrine transitions, such as the 
menstrual cycle (see review in ref. 28), underscoring the powerful 
role steroid hormones have in shaping the mammalian brain29. Endo-
crine changes across pregnancy dwarf those that occur across the 
menstrual cycle, which highlights the critical need to map the brain’s 
response to this unique hormonal state. Broad physiological changes 
occur in tandem with the rise in steroid hormones, including changes 
in body mass composition, water retention, immune function and 
sleep patterns11. These factors could have a role in the brain changes 
observed here, with some driving neurobiological changes and others, 
like water retention, potentially affecting MRI-based measurements. 
Note that, although cortical reductions in GMV over gestation were 
stable across analyses, accounting for QC measures influenced the 
magnitude and location of these results. These metrics all fell within 
the standard range, but there may be meaningful reductions in signal 
that accompany volumetric reductions (for example, increased CSF 
and decreased GM)—a methodological nuance that goes beyond the 
scope of this resource study. Ultimately, identifying the shared and 
unique contributions of these factors to the neuroanatomical changes 
that unfold across gestation warrants further investigation. Deeply 
phenotyping a large and diverse cohort of women across pregnancy will 
open up new avenues of exploration, for example, allowing research-
ers to link blood-based proteomic signatures to pregnancy outcomes; 
deploying wearable devices to monitor changes in sleep, cognition and 
mood; and probing the broader social and environmental determinants 
of maternal health27.
The neuroanatomical changes that unfold during matrescence 
may have broad implications for understanding individual differences 
in parental behavior13,24,30,31, vulnerability to mental health disorders32,33 
and patterns of brain aging 18,19,34–36. Decreases in GMV may reflect 
‘fine-tuning’ of the brain by neuromodulatory hormones in prepara -
tion for parenthood 26. For example, in rodents, steroid hormones 
promote parental behavior by remodeling specific neural circuits in the 
medial preoptic area of the hypothalamus. These behavioral adapta-
tions are critical to the dam’s ability to meet the demands of caring for  
a b
Quantitative anisotropy (zero centered)
Individual tracts
Corpus Callosum
R inf. fronto occipital fasc.
Gestation + postpartum
Summary white matter tracts
Gestation
StageStage
L inf. longitudinal fasc.
L arcuate fasciculus