Nature Neuroscience: doi:10.1038/nnL/R 0 -48 30 6.66 0.001 1162 -8 -57 21 6.53 0.001 8 -55 22 6.07...

Supplementary Figure 1

Plots of the remaining clusters

For the remaining clusters not indicated in the main figures (the left inferior orbitofrontal and the left middle frontal cluster, see Table 1), this figure depicts the (a) slice overlays,( b) plots representing the mean signal from the smoothed normalized jacobian difference images of the PRE and POST session, and (c) plots representing the mean (M±S.E.M.) signal change at each POST session relative to the pre-pregnancy baseline. FCTR=nulliparous control women, FPRG=women who were pregnant and transitioned into primiparity in-between sessions, Inf.= Inferior, Mid.= Middle, L=Left.

Nature Neuroscience: doi:10.1038/nn.4458


Effect sizes

(a) Illustration of the effect sizes (Cohen’s d) for the changes in GM volume in the women who were pregnant in-between sessions in comparison to the control women. All depicted effect sizes correspond to large effect sizes (Cohen’s d>0.8), although it should be noted that effect sizes from mapping experiments can be optimistically biased. Effect sizes were additionally computed separately for the GM volume changes in women achieving pregnancy by means of natural conception (b), and the women achieving pregnancy by fertility treatment (c). Yellow/orange tones correspond to reductions in GM volume across sessions in primiparous women in comparison to nulliparous control women, while blue tones represent relative increases in primiparous women in comparison to the control group. Effect sizes were extracted using the VBM8 toolbox (http://www.neuro.uni-jena.de/vbm/) and plotted in CARET (http://brainvis.wustl.edu).



Pituitary gland volume

Bar charts (a) and scatter plots (b) depicting pituitary gland volume in each session. The pituitary gland was manually delineated as a complementary analysis to further explore the data based on the previous findings of larger pituitary volume in pregnant women. Mean pituitary gland volume was about 40 mm

3 larger in the early postpartum session than in the PRE and the POST+2yrs sessions (M±SD:

PRE: 622.80±91.47 mm3. POST: 663±58-93.36 mm

3. POST+2yrs: 626.07±93.85 mm

3), although this PRE-to-POST increase is not

significant (GLM repeated measures: F=1.50, p=0.235). Accordingly, the observed increase of 7% in the POST session is subtle compared to the relative volume increases previously observed in late pregnancy, which fits with previous findings showing that the pituitary gland rapidly loses most of its volume gains shortly after birth. A significant reduction was observed between the early postpartum and the POST+2yrs session (F=21.32, p=0.001), suggesting that pituitary volumes in the POST session had not yet completely returned to pre-pregnancy levels yet. As expected, pituitary gland volume at the POST+2yrs session did not differ from the pre-pregnancy baseline (F=0.002, p=0.968).



Individual GM volume changes separated by means of conception

Plots representing mean signal from the smoothed normalized jacobian difference images averaged across cluster for the women achieving pregnancy by fertility treatment (FTRT, N=16), women achieving pregnancy by natural conception (FNAT, N=9) and nulliparous control women who were not pregnant in-between sessions (FCTR, N=20). Sup. Temp. Sulcus = Superior Temporal Sulcus, Med.= Medial, Inf.= Inferior, Mid.= Middle, L=left, R=right.



Surface-projected weight maps for multivariate classification

Projections of the average weight map, illustrating the relative importance of each voxel in the decision function, for the support vector machine classification results (see main manuscript) onto the brain’s surface.



Individual GM volume changes per cluster for all four groups

Plots representing mean signal from the smoothed normalized jacobian difference images for each group averaged across cluster. FCTR=nulliparous control women, FPRG= women who were pregnant and became first-time mothers in-between sessions. MCTR=nulliparous control men whose partners were not pregnant in-between sessions, MPRG= men whose partners were pregnant and who became first-time fathers in-between sessions, Sup. Temp. Sulcus = Superior Temporal Sulcus, Med.= Medial, Inf.= Inferior, Mid.= Middle, L=left, R=right.



Weight maps for multivariate regression results

Slice overlays depicting the average weight map, illustrating the relative importance of each voxel in the multivariate regression, for the kernel ridge regression analyses (see main manuscript). (a) Absence of hostility. (b) Quality of attachment.



Surface-projected weight maps for multivariate regression results

Projections of the average weight map, illustrating the relative importance of each voxel in the multivariate regression, for the kernel ridge regression analyses (see main manuscript) onto the brain’s surface. (a) Absence of hostility. (b) Quality of attachment.



Overlap structural changes and postpartum fMRI results

Slice overlays depicting the overlap between the changes in GM volume across pregnancy and the ‘own baby>other baby’ contrast of the postpartum fMRI paradigm. A red color indicates the area was present in both maps, while light and dark blue depict areas that were only present in either the structural or the fMRI map respectively.



Pre and Post plots

Illustration of GM signal in the PRE and POST sessions for the group of women who were pregnant in-between sessions and those who were not. Images were processed using a cross-sectional voxel-based morphometry approach. Due to the large inter-individual variability in GM values, the groups could not clearly be separated from one another visually when plotted in scatterplots, stressing the importance of using a pre-pregnancy baseline to map changes on an individual level. Therefore, bar charts depicting the group means (M±SEM) are provided for each of the regions. FCTR=nulliparous control women, FPRG=women who were pregnant and transitioned into primiparity in-between sessions, Sup. Temp. Sulcus = Superior Temporal Sulcus, Med.= Medial, Inf.= Inferior, Mid.= Middle, L=left, R=right.


11

Supplementary Table 1. Increases and decreases in GM volume

Contrasts

Regions H MNI coordinates T P Cluster size (# voxels) x y z

FPRG

increases

- -

FPRG

decreases

Superior Temporal Sulcus, Inferior/Middle/Superior Temporal Gyrus, Fusiform, Angular Gyrus, Hippocampus, Parahippocampal Gyus, Precuneus, Posterior Cingulate Cortex

L/R 2 -48 31 12.30 <0.001 53809

9 -54 24 11.14 <0.001

57 -18 -11 11.03 <0.001

Superior Medial Frontal Cortex, Anterior Cingulate Cortex, Medial Orbitofrontal Cortex

L Inferior/Middle/Superior Frontal Cortex, L Inferior Orbitofrontal Cortex, L Insula

L/R

0 50 12 11.08 <0.001 34000

-44 6 27 10.19 <0.001

-39 24 0 10.16 <0.001

Inferior/Middle/Superior Frontal Cortex

R 41 12 28 12.24 <0.001 6837

36 32 6 8.71 <0.001

41 -3 13 5.52 0.034

27 27 48 7.45 <0.001 674

Inferior Orbitofrontal Cortex, Temporal Pole

R 39 21 -21 6.63 0.001 152

Posterior Cerebellum L -12 -55 -47 6.04 0.005 156

R 18 -72 -27 5.95 0.007 81

FCTR

increases

-

FCTR

decreases

-

Following up on the significant group difference reported in Table 1, this table indicates the increases and

decreases in GM volume across sessions (‘PRE’ and ‘POST’) for the women who were pregnant in-between

sessions (FPRG) and the women who were not (FCTR). P value at peak voxel (whole-brain FWE-corrected at

voxel-level) is reported. H=hemisphere, L=left, R=right.


12

Supplementary Table 2. Total tissue volumes

Group Session TBV (ml, M±SD) GM (ml, M±SD) WM (ml, M±SD)

FPRG PRE 1076.10±91.97 667.70±56.00 408.41±41.79

POST 1059.18±88.51 644.69±57.30 414.49±42.38

FCTR PRE 1090.66±69.77 679.22±41.54 411.44±36.65

POST 1088.79±75.68 673.62±46.72 415.18±38.99

F=14.54, p<0.001 F=10.38, p=0.002 F=0.06, p=0.813

This table reports total tissue volumes in our sample, investigated as a supplementary analysis based on the findings of transient reductions in total brain size (defined by contouring the brain on MRI scans) during late pregnancy by Oatridge et al. Reductions were observed in total brain volume in the women who underwent pregnancy between the time points in comparison to control women, which were driven by reductions in total GM volume (see Supplementary Table 3 for our main analyses including total GM as a covariate). Total brain volume in the session around 2 years after birth was still at the level of the early postpartum rather than that of the pre-pregnancy session, and we observed a trend for volume reductions in the POST+2yrs session relative to the pre-pregnancy baseline (PRE: 1076.10±91.97 ml. POST: 1059.18±88.51 ml. POST+2years: 1053.22±81.09 ml. GLM repeated measures: F=3.39, p=0.096).There were no changes in total brain volume in the fathers in comparison to their control group of nulliparous men (MPRG: PRE: 1226.55±70.21 ml. POST: 1218.23±71.08 ml. MCTR: PRE: 1204.82±105.16. POST: 1199.45±101.93. (GLM rep measures: F=0.13, p=0.719). Our findings seem to be in accordance with those of Oatridge et al., although these cannot directly be compared since they investigated late pregnancy measures in comparison to the early postpartum period and no non-pregnant control group was included. However, our data are suggestive of a more stable reduction in total brain volume, perhaps in addition to a transient volume reduction during the pregnancy period itself as suggested by Oatridge et al.


13

Supplementary Table 3. Changes in GM volume between the PRE and POST sessions: Main model corrected for total GM changes

Contrasts


FPRG >

FCTR

-

FCTR >

FPRG

Superior Temporal Sulcus, Middle/Superior Temporal Gyrus

R 57 -18 -11 7.97 <0.001 1551

L -54 -18 -11 5.56 0.031 25

Precuneus, Posterior Cingulate

Cortex

L/R 0 -48 30 6.66 0.001 1162

-8 -57 21 6.53 0.001

8 -55 22 6.07 0.005


L/R 0 51 13 6.51 0.001 472

11 45 13 5.49 0.038

-14 53 4 5.51 0.036 12

Inferior Frontal Gyrus R 39 12 24 6.88 <0.001 540

Inferior Frontal Gyrus, Inferior Orbitofrontal Gyrus, Insula

L -41 23 -2 6.34 0.002 207

Middle/Superior Frontal Gyrus L -24 26 45 5.62 0.025 57

Fusiform, Inferior Temporal Gyrus

R 33 -37 -14 6.05 0.005 125

L -45 -54 -14 5.77 0.014 145

MPRG >

MCTR

-

MCTR >

MPRG

-

Comparisons of GM volume changes across sessions (‘PRE’ and ‘POST’) between the primiparous and nulliparous control groups, extracted from a model including the change in total grey matter volume as a covariate (see Supplementary Box 1 for a discussion of these results). P value at peak voxel (whole-brain FWE-corrected) is reported. The same clusters as observed in the main model are also present in the current model, although these are less extensive, likely reflecting a dependence of the reductions in the sum of GM across all voxels on the observed local reductions in GM volume, The left hippocampal and left inferior frontal cluster (i.e. the clusters of the main model that are not present in the current model) are just below the FWE-corrected threshold (P=0.085 and P=0.051 FWE-corrected respectively). H=hemisphere, L=left, R=right, FPRG = women who were pregnant and became first-time mothers in-between sessions, FCTR

= nulliparous control women who were not pregnant in-between sessions, MPRG = men whose partners were pregnant and who became first-time fathers in-between sessions, MCTR = nulliparous control men whose partners were not pregnant in-between sessions.


14

Supplementary Table 4. Comparisons of GM volume changes based on conception method

Contrasts


FPRG_NAT>

FPRG_ASS

- -

FPRG_ASS>

FPRG_NAT

-

FCTR>

FPRG_NAT

Superior Temporal Sulcus, Inferior/Middle/Superior Temporal Gyrus, Angular Gyrus, Parahippocampal Gyrus, Hippocampus, Fusiform Gyrus

R 44 -33 -6 6.96 *<0.0001 8652

36 -31 -14 6.81 *<0.0001

57 -16 -14 6.54 *<0.0001

42 -49 27 4.94 <0.0001 1036

53 -45 19 4.51 <0.0001

L -51 -22 -8 5.71 <0.0001 5614

-39 -57 24 5.61 <0.0001

-54 -30 -5 5.56 <0.0001


Cortex

L/R -5 54 24 6.24 *<0.0001 3088

9 -54 22 5.65 <0.0001

Superior Medial Frontal Cortex, Anterior Cingulate Cortex, Orbitofrontal Cortex

L/R 0 54 13 4.71 <0.0001 368

2 53 -3 4.50 <0.0001 93

39 24 -23 4.46 <0.0001 44

-17 51 4 4.44 <0.0001 124

-26 51 9 4.21 <0.0001

-27 57 -2 4.40 <0.0001 53

2 36 24 4.22 <0.0001 17


38 33 9 5.03 <0.0001 296

L -44 8 31 4.72 <0.0001 363

Inferior Orbitofrontal Gyrus, Insula L -38 27 1 5.39 <0.0001 821

Middle/Superior Frontal Gyrus R 30 23 51 4.72 <0.0001 335

L -24 23 45 4.65 <0.0001 240

FPRG_NAT>

FCTR

-

FCTR>

FPRG_ASS

Superior Temporal Sulcus,

Inferior/Middle/Superior Temporal Gyrus, Cerebellum, Fusiform Gyrus

R 59 -16 -12 7.94 *<0.0001 8492

56 -42 -5 5.88 *<0.0001

30 -39 -12 5.82 <0.0001

L -53 -18 -11 6.18 *<0.0001 4959

-56 -33 -9 5.65 <0.0001

-62 -40 -11 5.42 <0.0001

-12 -54 -44 4.81 <0.0001 132

Precuneus, Posterior Cingulate Cortex

L/R -5 -55 -18 7.45 *<0.0001 702

Superior Medial Frontal Cortex,

Anterior Cingulate Cortex, Medial Orbitofrontal Cortex

L/R 0 56 12 4.61 <0.0001 4650

0 44 -9 4.54 <0.0001

12 45 13 4.41 <0.0001

Inferior Frontal Gyrus, Insula R 39 14 25 5.64 <0.0001 674

35 29 7 4.28 <0.0001 68

L -51 12 16 4.94 <0.0001 719

-45 9 31 4.60 <0.0001


15

Inferior Orbitofrontal Gyrus, Insula L -44 23 -8 4.98 <0.0001 564

Middle/Superior Frontal Gyrus L -23 30 45 5.39 <0.0001 1313

Hippocampus, Parahippocampal Gyrus

L -32 -21 -18 6.26 *<0.0001 702

Amygdala L -24 0 -27 5.32 <0.0001 274

FPRG_ASS>

FCTR

-

Comparisons of GM volume changes across sessions (‘PRE’ and ‘POST’) between the subgroups of women who got pregnant by natural or assisted conception (fertility treatment) and nulliparous control women. P value at peak voxel is reported. Considering the smaller subgroups available for these analyses, the results were also inspected and are reported at the more lenient threshold of p<0.0001. The clusters also surfacing with the p<0.05 FWE-corrected threshold are indicated with an asterisk. H=hemisphere, L=left, R=right, FCTR

= nulliparous control women who were not pregnant in-between sessions, FPRG_ASS = women who were pregnant in-between sessions and achieved pregnancy by fertility treatment, FPRG_NAT =women who were pregnant in-between sessions and achieved pregnancy by natural conception.


16

Supplementary Table 5. Increases and decreases in GM volume in subgroups based on conception method

Contrasts


FPRG_NAT

increases

-

FPRG_NAT

decreases

Superior Temporal Sulcus, Middle/Superior Temporal Gyrus, Angular Gyrus, Parahippocampal Gyrus, Hippocampus, Fusiform Gyrus

R 45 -33 -6 8.45 <0.001 2699

36 -31 -14 7.17 0.001

57 -15 -14 6.97 0.002

48 -48 22 6.69 0.005 860

L -51 -22 -8 7.17 0.001 1548

-53 -1 -18 7.09 0.002

-41 -57 25 7.82 <0.001 1980

-48 -49 13 6.35 0.013

-35 -19 -15 7.06 0.002 145


L/R -2 -51 27 8.49 <0.001 3182

11 -54 25 7.97 <0.001

2 36 24 4.22 <0.0001 17

Superior Medial Frontal Cortex, Anterior Cingulate Cortex, Middle Cingulate Cortex, L Middle/Superior Frontal Gyrus

L/R -3 47 18 6.65 0.006 567

0 35 24 6.55 0.007

-8 -24 40 6.17 0.021 27

-18 48 6 6.53 0.008 190

-26 51 10 6.18 0.021

Inferior Frontal Gyrus, Middle

Frontal Gyrus, Precentral Gyrus, Insula, L Inferior Orbitofrontal Gyrus

R 42 12 31 9.07 <0.001 1867

38 33 9 7.07 0.002 202

L -38 30 3 7.81 <0.001 1774

-42 5 30 7.81 0.001

-50 12 18 7.35 0.010

Fusiform, Inferior Temporal Gyrus L -45 -55 -15 6.77 0.004 534


R 39 24 -23 6.60 0.006 93

FPRG_TRT

increases

-

FPRG_TRT

decreases


Middle/Superior Temporal Gyrus, Parahippocampal Gyrus, Fusiform Gyrus

R 57 -21 -9 8.93 <0.001 3263

56 -40 -3 7.28 0.001

27 -42 -9 7.25 0.001 330

L -51 -18 -9 8.03 <0.001 3617

-62 -42 -11 7.58 <0.001

-47 -57 -14 6.79 0.004


Cortex

L/R 2 -49 30 10.14 <0.001 4788



L/R 0 50 12 7.52 <0.001 3832

0 38 19 7.25 0.001

-29 51 10 7.02 0.002

Inferior Frontal Gyrus, Precentral Gyrus, R Insula

R 41 12 28 8.81 <0.001 963

36 30 6 6.71 0.005 254

L -50 12 18 7.47 0.001 1370

-44 6 30 7.46 0.001


17


Angular Gyrus L -45 -63 30 6.19 0.020 181


L -33 -21 -17 8.50 <0.001 416

FCTR

increases

-

FCTR

decreases

-

Following up on the significant group difference reported in Supplementary Table 4, this table indicates the increases and decreases in GM volume across sessions (‘PRE’ and ‘POST’) for the subgroups of women who got pregnant by natural or assisted conception (fertility treatment) and the nulliparous control women. P value at peak voxel (whole-brain FWE-corrected at voxel-level) is reported. H=hemisphere, L=left, R=right, FCTR = nulliparous control women who were not pregnant in-between sessions, FPRG_ASS = women who were pregnant in-between sessions and achieved pregnancy by fertility treatment, FPRG_NAT =women who were pregnant in-between sessions and achieved pregnancy by natural conception.


18

Supplementary Table 6. Quantification of spatial similarity between GM volume changes of

pregnancy and functional maps

Map1 Volume map (mm3)

Observed overlap (mm3)

Observed overlap (%Map1)

Observed overlap (%ẟPRG)

Expected overlap

(mm3)

Observed / expected overlap

fMRI own baby>baby

8748

2535 28.97 6.13 367.06 6.91

TOM network3

67308

8502 12.63 20.57 2824.17 3.01

Functional networks of the cerebral cortex4

Comp 1 229105 287 0.13 0.69 9613.05 0.03

Comp 2 221549 1856 0.84 4.49 9295.98 0.20

Comp 3 183971 15171 8.25 36.70 7719.27 1.97

Comp 4 235852 5599 2.37 13.55 9896.13 0.57

Comp 5 194876 6581 3.38 15.92 8176.82 0.80

Comp 6 194214 122 0.06 0.29 8149.07 0.01

Comp 7 206442 982 0.48 2.38 8662.13 0.11

Comp 8 218987 3267 1.49 7.90 9188.50 0.36

Comp 9 217411 5802 2.67 14.03 9122.37 0.64

Comp 10 180326 19821 10.99 47.95 7566.33 2.62

Comp 11 194241 15218 7.83 36.81 8150.20 1.87

Comp 12 184910 4678 2.53 11.32 7758.64 0.60

The overlap of the changes in GM volume across pregnancy were quantified with: a) the mothers’ neural response to seeing their baby (‘own baby>other baby’ contrast, see Figure 6 and Supplementary Table 9), b) the Theory of Mind network as defined by the meta-analysis of Schurz et al.

3, and c) the cognitive networks of

the large-scale meta-analysis of cerebral functional network organization by Yeo et al.4. The tasks recruited by

the cognitive components of Yeo et al. are depicted in an interactive map (https://surfer.nmr.mgh.harvard.edu/fswiki/BrainmapOntology_Yeo2015). The overlap of our results with these functional networks was extracted by computing the intersection between each of these maps and the GM volume changes of pregnancy (column ‘Observed overlap’). The percentages of each of the maps represented by the overlap were subsequently determined and reported in percentage of the functional map (column ‘Observed overlap (%Map1))’ and in percentage of the map of GM volume changes of pregnancy (column ‘Observed overlap (%ẟPRG))’. The expected overlap based on a random distribution across the brain was determined by multiplying the percentages of the brain’s total GM (an estimate of total GM was obtained by segmenting the canonical T1-weighted image provided by SPM) represented by each of the 2 maps. The percentage of expected overlap was then multiplied by total GM (column ‘Expected overlap’), and the expected overlap was divided by the observed overlap (column ‘Observed>Expected overlap’). The rows in bold indicate those components that are recruited by Theory of Mind tasks, with component 10 representing the component of strongest Theory of Mind recruitment (0.55%). Note that these 3 components recruited by Theory of Mind tasks also correspond to the only ones showing a stronger overlap with the GM changes of pregnancy than expected based on random distribution across the brain’s grey matter tissue. Comp= component. TOM = Theory of Mind, ẟPRG = changes in GM volume across pregnancy.


19

Supplementary Table 7. Changes in GM volume between the PRE and POST sessions: Comparison across the four groups

Contrasts


FCTR(post-pre) >

FPRG(post-pre) >

(MCTR(post-pre)>

MPRG(post-pre))


Middle/Superior Temporal Gyrus

R 56 -16 -11 5.48 *<0.001 1631

48 -33 -3 4.95 <0.001

Precuneus, Posterior Cingulate Cortex L/R -5 -55 22 5.42 *<0.001 1287


L/R 0 50 13 4.88 <0.001 808

-14 53 4 4.52 <0.001

Inferior Frontal Gyrus R 41 14 25 5.69 *<0.001 1294

36 32 9 3.92 <0.001 3

L -44 5 28 3.93 <0.001 3

Inferior Orbitofrontal Gyrus, Inferior

Frontal Gyrus, Insula

L -35 26 -5 4.27 <0.001 87

Middle/Superior Frontal Gyrus L 29 27 49 4.32 <0.001 134

R -23 23 46 4.28 <0.001 67

Fusiform, Inferior Temporal Gyrus R 48 -51 -15 4.19 <0.001 116

33 -39 -14 4.09 <0.001 38

L -27 -54 -8 4.23 <0.001 161

-45 -51 -12 3.97 <0.001 15

Hippocampus, Parahippocampal Gyrus, Amygdala

L -32 -18 -21 4.19 <0.001 161

-38 -10 -21 4.16 <0.001

-27 3 -29 4.24 <0.001 52

Results of the contrast FCTR(post>pre)>FPRG(post>pre)>(MCTR(post>pre)>MPRG(post>pre)), applied to confirm that the reductions in the primiparous women in comparison to the nulliparous control women were also observed when comparing these to the primiparous fathers (in comparison to their own control group). The clusters that surface at the whole-brain voxel-wise threshold of P=0.05 FWE-corrected results are indicated with an asterisk. However, considering the complexity of the interaction results, these results were also examined using the more lenient statistical threshold of p<0.0001 uncorrected. H=hemisphere, L=left, R=right, FPRG = women who were pregnant and became first-time mothers in-between sessions, FCTR = nulliparous control women who were not pregnant in-between sessions, MPRG = men whose partners were pregnant and who became first-time fathers in-between sessions, MCTR = nulliparous control men whose partners were not pregnant in-between sessions.


20

Supplementary Table 8. Changes in surface area and cortical thickness across pregnancy

Contrasts

Regions H MNI coordinates -log (10)P

Size (SA: mm2, CT: mm) x y z

SURFACE AREA

FPRG

increases

-

FPRG

decreases

Inferior Frontal Gyrus L -50.3 15.3 21.9 -5.90 257.84

-45.6 37.1 -0.5 -4.15 82.9

R 54.3 22.9 10.9 -6.34 355.05

Middle Temporal Gyrus L -61.3 -45.3 -5.8 -5.2 474.6

R 46.9 5.6 -35.7 -4.60 89.77

Superior Temporal Sulcus R 57.2 -41.9 -4.6 -4.03 91.99

Precuneus L -15.6 -45.4 35.2 -4.69 86.6

R 8.4 -54.5 21.1 -5.43 561.51

Posterior Cingulate Cortex R 3.8 -16.7 33.3 -4.69 79.55

Orbitofrontal Cortex R 37.3 42.6 -10.1 -4.56 95.36

Middle Frontal Gyrus R 41.8 22.2 28.2 -4.38 68.93

Fusiform Gyrus L -40.3 -43.11 -19.2 -4.91 84.09

-29.9 -76.9 -10.7 -4.58 105.75

R 37.1 -8 -31.7 -5.60 170.09

Inferior Temporal Gyrus R 53.5 -39.1 -17.5 -5.09 299.45

Lingual Gyrus L -7.6 -85.7 -6.8 -5.86 474.6

R 4.8 -84 -2.7 -8.69 1129.93

Inferior Parietal Gyrus L -46.5 -56.9 40.8 -4.78 92.94

R 48.8 -54.7 15.5 -6.60 171.79

41 -78.5 26.1 -5.33 231.3

CORTICAL THICKNESS

FPRG

increases

-

FPRG

decreases

Middle Temporal Gyrus R 56.7 -44.1 -10.9 -4.67 182.49

Superior Temporal Sulcus L -48.7 -42.5 0.7 -6.63 572.59


Fusiform Gyrus L -41.3 -53.4 -16.3 -6.78 684.27

R 27.0 -75.0 -6.7 -5.08 250.03

Lingual Gyrus L -30.5 -55.3 -7.5 -7.72 184.83

Inferior Parietal Cortex L -37.4 -73.5 36.6 -5.60 247.86

Lateral Occipital Cortex R 25.9 -98 -2.8 -5.66 202.32

Changes in surface area and cortical thickness between pre-pregnancy and post-pregnancy session are indicated for the primiparous women. Longitudinal change in cortical surface area and thickness in each hemisphere was calculated as symmetrized percent change (i.e. the rate of change between the time points with respect to the average thickness/area across the time points). Table indicates the coordinates, size, anatomical label and -log10(p-value) of the peak vertex of the cluster. The cluster statistics were obtained using Monte Carlo simulations with a vertex-wise -log10(p-value) of 4 (corresponding to p<0.0001) and a cluster-wise threshold of p<0.05. H=hemisphere, L=left, R=right, SA=Surface Area, CT=Cortical Thickness, FPRG = women who were pregnant and transitioned into primiparity in-between sessions.


21

Supplementary Table 9. Comparisons of changes in surface area and cortical thickness Contrasts

Regions H MNI coordinates -log

(10)P

Size (SA: mm2, CT: mm) x y z

SURFACE AREA

FPRG>

FCTR

-

FCTR >

FPRG

Middle Temporal Gyrus R 44.3 7.0 -37.1 -5.84 205.62


Superior Frontal Gyrus R 19.5 26.5 49.4 -4.98 123.65

Fusiform Gyrus R 33.5 -1.2 -41.7 -4.54 73.7

Lingual Gyrus L -7.3 -85.3 -6.1 -4.06 79.26

R 4.4 -84.3 -4.8 -4.64 149.92

Inferior Parietal Cortex R 49.5 -55.4 15.8 -6.92 98.42

42.3 -75.2 24.9 -4.52 87.64

MPRG >

MCTR

MCTR >

MPRG

CORTICAL THICKNESS

FPRG>

FCTR

-

FCTR >

FPRG

Fusiform Gyrus L -42 -55.6 -17.8 -4.90 171.21

MPRG >

MCTR

-

MCTR >

MPRG

-

Comparisons of changes in surface area and cortical thickness across sessions (‘PRE’ and ‘POST’) between the primiparous and the nulliparous control groups. Longitudinal change in cortical surface area and thickness in each hemisphere was calculated as symmetrized percent change (i.e. the rate of change between the time points with respect to the average thickness/area across the time points), Table indicates the coordinates, size, anatomical label and -log10(p-value) of the peak vertex of the cluster. The results were thresholded at a -log10(p-value) of 4 cluster- corrected using Monte Carlo simulations. H=hemisphere, L=left, R=right, FPRG = women who were pregnant and became first-time mothers in-between sessions, FCTR = nulliparous control women who were not pregnant in-between sessions, MPRG = men whose partners were pregnant and who became first-time fathers in-between sessions, MCTR = nulliparous control men whose partners were not pregnant in-between sessions.


22

Supplementary Table 10. Cognitive test and questionnaire data

Measure Gender PRG

Mdn(IQR)

CTR

Mdn(IQR)

U P

TAVEC

Correct

(post-pre)

F 0.00 (8.00) 5.00(8.25) 121.5 0.074

M -1.00(10.50) 4.00(17.00) 69.0 0.249

Intrusion

(post-pre)

F -1.00(2.00) 0.00(0.75) 144.5 0.237

M -1.00(2.50) 0.00(2.00) 73.0 0.322

Perseverance

(post-pre)

F 0.00(5.00) -1.50(4.50) 157.5 0.447

M 0.00(2.50) -2.00(6.00) 77.0 0.429

WAIS Digits (post-pre) F 1.00 (3.00) 0.00 (3.75) 165.0 0.344

M 1.00 (4.00) 0.00(2.00) 74.0 0.182

N-Back total correct (post-

pre)

F -1.37 (6.85) 0.00 (5.48) 138.5 0.410

M 0.00 (4.79) -1.35 (6.85) 76.0 0.145

RT (post-pre) F 13.70 (25.00) 7.87 (38.33) 163.0 0.951

M 15.49 (21.36) 7.38(31.52) 78.0 0.174

IRI

PT (post-pre) F 1.00(5.00) 0.00(4.00) 165.5 0.537

M 0.00(6.00) 1.00(6.25) 63.0 0.264

FS (post-pre) F -2.00(8.50) -2.00(5.00) 185.5 0.955

M -2.00(2.50) 0.00(6.00) 53.0 0.104

EC (post-pre) F 0.00(4.00) 0.00(3.00) 183.5 0.910

M 0.00(3.50) 0.00(5.25) 67.0 0.363

PD (post-pre) F 1.00(4.00) -3.00(7.00) 131.5 0.116

M 1.00(6.50) -0.50(5.50) 84.5 0.980

Comparisons of changes in the scores on the cognitive test and questionnaire data across sessions (‘PRE’ AND

‘POST’ sessions) between the primiparous and nulliparous control groups. Shapiro-Wilk tests indicated that some of

these variables did not follow a normal distribution, and therefore non-parametric two-tailed Mann-Whitney U tests

were applied. Equal variances were confirmed using the non-parametric Levene’s test. There were no significant

changes in performance on these measures, although it should be noted that larger sample sizes would be required

to more reliably examine this type of data and reveal subtle effects. For the TAVEC, complete PRE/POST datasets

are available of 23 primiparous women, 16 nulliparous control women, 17 primiparous fathers and 11 nulliparous

control men (not all subjects participated in these tests in both sessions). For the N-back and RT test this is

22/15/17/13, for the Digits test: 25/16/19/11, for the IRI: 25/15/17/10. TAVEC = Test de Aprendizaje Verbal España-

Complutense, based on the California Verbal Learning Test, Digits = the Digits subtest of the Wechsler Adult

Intelligence Scale III, N-back = a visual 2-back test, IRI = Interpersonal Reactivity Index, PT = Perspective Taking, FS

= Fantasy Scale, EC = Empathic Concern, PD = Personal Distress, RT = a simple visual reaction time task, F =

Female, M = Male, PRG = Participants who became first-time parents in-between sessions, CTR = Nulliparous

control participants, Mdn= Median, IQR = Interquartile range.


23

Supplementary Table 11. Neural activity in response to own versus other baby pictures

Contrasts


own baby>

other baby

Inferior Frontal Gyrus R 48 34 8 7.72 **<0.0001 222

42 12 18 6.31 <0.0001 300

54 12 24 5.60 <0.0001

46 10 28 5.54 <0.0001

Posterior Cingulate Cortex,

Precuneus L/R 0 -48 26 6.38 *<0.0001 205

-10 -44 26 5.88 <0.0001

6 -40 20 5.46 <0.0001


Medial Orbitofrontal Cortex L -8 60 -4 5.61 <0.0001 72

Middle Temporal Gyrus, Inferior Temporal Gyrus, Fusiform

R 44 -40 -16 5.35 <0.0001 63

52 -56 0 5.19 <0.0001

46 -50 -8 4.97 <0.0001

Temporal Pole R 38 22 -24 5.46 <0.0001 20

40 14 -32 5.37 <0.0001

Caudate, Ventral Striatum L/R -6 12 -2 5.95 <0.0001 90

2 14 0 5.32 <0.0001

2 4 0 4.73 <0.0001

Thalamus R 8 -2 0 5.02 <0.0001 16

Middle Occipital Gyrus R 40 -62 20 6.14 <0.0001 64

34 -70 28 5.48 <0.0001

32 -60 28 5.17 <0.0001

other baby>

own baby

-

Results of the baby picture fMRI paradigm in the POST session (N=20). The mothers’ neural response to seeing pictures of their own baby were contrasted against the neural activity in response to pictures of other babies. P value at peak voxel is reported. The clusters that are significant at the P<0.05 FWE-corrected are indicated, but for exploratory purposes, the results were also examined at the more lenient threshold of p<0.0001. * P<0.05 FWE-corrected. **Trend (P<0.10) FWE-corrected. H=hemisphere, L=left, R=right.


24

Supplementary Table 12. Neural activity in response to own or other baby pictures

Contrasts


Own baby Fusiform, Inferior Temporal Cortex,

Inferior Occipital Cortex

R 40 -48 -14 7.71 *<0.0001 1010

44 -56 -12 7.13 *<0.0001

40 -40 -22 6.86 *<0.0001

L -42 -56 -18 5.90 <0.0001 67

Hippocampus, Parahippocampal Gyrus, Amygdala

R -40 -76 -8 5.60 <0.0001 35

22 -6 -20 7.13 *<0.0001 125

30 -12 -16 5.71 <0.0001

Cerebellar Vermis R 4 -40 -20 6.71 *<0.0001 56

Other baby Fusiform, Inferior Temporal Cortex, Inferior Occipital Cortex

R 38 -50 -20 7.02 *<0.0001 475

48 -70 -4 5.93 <0.0001

40 -74 -8 5.48 <0.0001

Hippocampus, Parahippocampal

Gyrus, Amygdala R

20 -4 -18 5.54 <0.0001 20

Cerebellar Vermis L 2 -40 -18 5.27 <0.0001 14

Results of the baby picture fMRI paradigm in the POST session for the ‘own baby’ and the ‘other baby’ conditions separately (N=20). P value at peak voxel is reported. The clusters that are significant at the P<0.05 FWE-corrected are indicated, but, for exploratory purposes, the results were also examined at the more lenient threshold of p<0.0001. * P<0.05 FWE-corrected. **Trend (P<0.10) FWE-corrected. H=hemisphere, L=left, R=right.


25

Supplementary Table 13. Changes in GM volume in the POST+2years session compared to the pre-pregnancy and early postpartum sessions

Contrasts


PRE vs POST+2yrs

Increases -

Decreases Superior Temporal Sulcus,


R 36 -42 -9 11.71 <0.001 2791

50 -7 -11 8.83 0.002

42 -28 -5 7.43 0.007

L -59 -15 -11 12.55 <0.001 866

-53 -37 -8 9.07 0.002

-60 -37 -2 9.04 0.002

Precuneus, Posterior Cingulate Cortex, Cuneus

L/R 9 -46 34 8.47 0.003 1362

11 -57 31 7.84 0.005

-11 -61 22 5.84 0.031 36


L/R -2 48 -6 9.06 0.002 1686

-3 48 21 8.87 0.002

-17 51 1 8.19 0.003


44 18 18 10.04 0.001

L -47 12 30 8.98 0.002 161

-51 15 18 8.50 0.003

Inferior Orbitofrontal Gyrus, Inferior Frontal Gyrus, Insula

L -44 24 -5 9.31 0.001 283

-38 32 -3 8.17 0.004


-21 38 48 5.47 0.045 11


R 42 -52 20 5.78 0.033 12

L -48 -49 -9 10.66 0.001 666

-33 -42 -20 6.81 0.012

POST vs POST+2yrs

Increases Hippocampus L -33 -21 -15 5.90 0.030 14

Decreases -

Changes in GM volume in the session around 2 years after giving birth relative to the pre-pregnancy baseline and to the early postpartum session. Complete PRE-POST-POST+2yrs datasets were available of 11 women. P value at peak voxel (P<0.05 FWE-corrected) is reported, restricted to regions affected by pregnancy with an explicit mask of the main contrast. H=hemisphere, L=left, R=right


26

Supplementary Table 14. Increases and decreases in GM volume in primiparous women: model including a covariate for the duration of the postpartum period until the POST session

Contrasts


FPRG

increases

-

FPRG

decreases

Superior Temporal Sulcus, Middle/Superior Temporal Gyrus,

L Angular Gyrus

R 57 24 -8 10.56 <0.001 3772

62 -9 -15 9.82 <0.001

L -51 -19 -11 9.78 <0.001 4546

-56 -33 -6 9.22 0.001

-48 -55 -15 8.23 0.006

-47 -64 30 8.55 0.003 1026


Cortex, R Fusiform

L/R 2 -49 33 12.90 <0.001 7228

29 -45 -9 11.27 <0.001

-2 -25 42 8.93 0.002


L Inferior/Middle/Superior Frontal Cortex, L Inferior Orbitofrontal Cortex, L Insula

L/R

-47 23 21 11.00 <0.001 14611

-45 6 31 10.42 <0.001

-39 18 37 9.97 <0.001

Inferior/Middle/Superior Frontal

Cortex

R 41 9 28 11.50 <0.001 1855

39 30 7 7.71 0.014

41 27 0 7.64 0.016

30 59 3 8.31 0.005 320

29 29 48 8.11 0.007 140


R 33 36 -23 8.46 0.004 256

41 23 -20 7.68 0.015

Hippocampus, Parahippocampal Gyus, Fusiform, Inferior Temporal Gyrus

L -35 -21 -17 10.85 <0.001 691

-24 -24 -20 8.32 0.005

-48 -4 -33 7.06 0.043 12

Changes in GM volume across sessions (‘PRE’ and ‘POST’) for the women who underwent pregnancy in-

between sessions (FPRG), extracted from a model including the time interval (days) between birth and the POST session as a covariate. P value at peak voxel (P<0.05 FWE-corrected at voxel-level) is reported. H=hemisphere, L=left, R=right.


27

Supplementary Table 15: Changes in GM volume between the PRE and POST sessions: Model excluding the women with a relatively longer time interval between the PRE session and conception

Contrasts


FPRG >

FCTR

- -

FCTR >

FPRG


R 57 -18 -11 8.05 0.001 2169

L -54 -18 -11 5.72 0.017 81


L/R 0 -48 30 7.04 <0.001 1574

-6 -58 21 6.66 0.001

6 -55 24 6.35 0.002


L/R 0 53 13 6.84 <0.001 654

-14 53 14 5.79 0.014


Inferior Orbitofrontal Gyrus,

Insula

L -38 24 -2 6.37 0.002 162


Fusiform, Inferior Temporal

Gyrus, Parahippocampal Gyrus

R 33 -36 -14 6.15 0.004 250

33 -24 -18 5.88 0.010

L -42 -54 -15 5.70 0.019 97


L -30 -19 -18 5.96 0.008 124

MPRG >

MCTR

-

MCTR >

MPRG

-

Comparisons of GM volume changes across sessions (‘PRE’ and ‘POST’) between the primiparous and nulliparous control groups, extracted from a model including only the 20 women with an estimated pregnancy onset within 6 months after the first session. P value at peak voxel (whole-brain FWE-corrected) is reported. H=hemisphere, L=left, R=right, FPRG = women who were pregnant and became first-time mothers in-between sessions, FCTR = nulliparous control women who were not pregnant in-between sessions, MPRG = men whose partners were pregnant and who became first-time fathers in-between sessions, MCTR = nulliparous control men whose partners were not pregnant in-between sessions.


28

Supplementary Table 16: Changes in GM volume between the PRE and POST sessions: Model including a covariate for age

Contrasts


FPRG >

FCTR

- -

FCTR >

FPRG


R 57 -18 -11 8.80 <0.001 3184

54 -37 -3 7.20 <0.001

L -56 -33 -6 6.59 0.001 1177

-53 -19 -11 6.47 0.001


L/R 0 -48 30 7.49 <0.001 2491

-6 -57 21 7.24 <0.001

6 -55 22 6.87 <0.001


L/R 0 53 12 6.97 <0.001 1447

0 48 -6 6.06 0.007

-14 53 4 5.70 0.011


L -50 12 16 5.88 0.034 182

-44 8 28 5.62 0.024


Insula

L -39 24 -2 6.52 0.001 65


Fusiform, Inferior Temporal Gyrus, Parahippocampal Gyrus,

Hippocampus

R 33 -37 -14 6.73 0.002 554

33 -24 -18 6.05 0.005

L -44 -54 -14 6.59 0.001 734

-35 -42 -17 5.50 0.037

-32 -21 -18 5.95 0.007 115

MPRG >

MCTR

-

MCTR >

MPRG

-

Comparisons of GM volume changes across sessions (‘PRE’ and ‘POST’) between the primiparous and nulliparous control groups, extracted from a model including a covariate for age. P value at peak voxel (P<0.05 whole-brain FWE-corrected) is reported. H=hemisphere, L=left, R=right, FPRG = women who were pregnant and became first-time mothers in-between sessions, FCTR = nulliparous control women who were not pregnant in-between sessions, MPRG = men whose partners were pregnant and who became first-time fathers in-between sessions, MCTR = nulliparous control men whose partners were not pregnant in-between sessions.


29

Supplementary Table 17: Changes in GM volume between the PRE and POST sessions: Model including a covariate for age, time interval between sessions and level of education

Contrasts


FPRG >

FCTR

- -

FCTR >

FPRG



R 57 -18 -11 8.84 <0.001 2754

54 -37 -2 7.04 <0.001

L -54 -19 -11 6.20 <0.001 861

-56 -33 -6 6.41 0.004


L/R 0 -48 30 7.16 <0.001 1975

-8 -57 21 6.88 <0.001

8 -55 22 6.46 0.001


L/R 0 53 12 6.96 <0.001 1435

2 51 -3 6.06 0.006

-12 54 4 5.70 0.020


L -50 12 16 5.55 0.034 13

Inferior Orbitofrontal Gyrus, Insula

L -39 24 -2 6.52 0.001 286


Fusiform, Inferior Temporal Gyrus, Parahippocampal Gyrus

R 33 -37 -14 6.34 0.002 270

32 -24 -18 5.75 0.017

L -44 -54 -14 6.30 0.002 424

-32 -21 -18 5.71 0.019 47

MPRG >

MCTR

-

MCTR >

MPRG

-

Comparisons of GM volume changes across sessions (‘PRE’ and ‘POST’) between the primiparous and nulliparous control groups, extracted from a model including a covariate for age, time interval between the sessions and level of education. P value at peak voxel (P<0.05 whole-brain FWE-corrected) is reported. H=hemisphere, L=left, R=right, FPRG = women who were pregnant and became first-time mothers in-between sessions, FCTR = nulliparous control women who were not pregnant in-between sessions, MPRG = men whose partners were pregnant and who became first-time fathers in-between sessions, MCTR = nulliparous control men whose partners were not pregnant in-between sessions.


30

Supplementary Table 18. Increases and decreases in GM volume in subgroups based on conception method (natural conception and a fertility-treated group selected for homogeneous hormone therapy)

Contrasts


FPRG_NAT

increases

-

FPRG_NAT

decreases

Superior Temporal Sulcus, Inferior/Middle/Superior Temporal Gyrus, Angular Gyrus, Parahippocampal Gyrus, Hippocampus, Fusiform Gyrus

R 47 -33 -5 8.84 <0.001 2237

29 -42 -6 6.79 0.009

57 -13 -15 7.27 0.003

47 -54 -20 6.50 0.018 95

51 -46 19 6.30 0.030 203

47 -51 25 6.26 0.033

L -35 -34 -12 8.00 <0.001 2108

-53 -3 -17 7.29 0.003

-41 -27 -8 7.08 0.004

-41 -57 25 7.62 0.001 1359


Cortex

L/R -2 -51 28 8.21 <0.001 2757

11 -54 25 7.94 0.001


Anterior Cingulate Cortex,

L Superior Frontal Gyrus

L/R -2 38 27 7.04 0.005 638

-18 48 6 6.53 0.017 61

Inferior Frontal Gyrus, Middle Frontal Gyrus, Precentral Gyrus,

L Insula, L Inferior Orbitofrontal Gyrus

R 42 14 30 10.11 <0.001 2095

36 33 12 7.13 0.004 231

L -38 29 1 8.22 <0.001 761

-41 5 31 7.15 0.004 352


R 39 24 -23 6.37 0.025 17

FPRG_TRT

increases

-

FPRG_TRT

decreases

Superior Temporal Sulcus, Middle/Superior Temporal Gyrus,

L Parahippocampal Gyrus,

L Hippocampus

R 53 -42 -2 8.28 <0.001 2297

59 -10 -17 7.96 <0.001

54 -27 -8 7.92 0.001

L -33 -31 -14 7.60 0.001 1087

-53 -6 -15 6.91 0.007

-50 -15 -11 6.88 0.007


Cortex

L/R 6 -48 34 9.15 <0.001 3377

-3 -52 27 8,83 <0.001


Anterior Cingulate Cortex,

L Superior Frontal Gyrus

L/R -2 39 24 6.92 0.006 1232

26 54 12 6.80 0.009

-14 38 30 6.38 0.025

-17 51 6 6.72 0.011 129

Inferior Frontal Gyrus, Precentral Gyrus

R 41 14 31 9.10 <0.001 1128

L -39 5 31 6.70 0.011 311

-50 14 18 6.23 0.036 21


-29 48 9 6.28 0.032 33

FCTR

increases

-


31

FCTR

decreases

-

Changes in GM volume across sessions (‘PRE’ and ‘POST’) for the subgroups of women who were pregnant in-between sessions based on type of conception (natural conception or fertility treatment). For the fertility-treated women, a homogeneous subgroup undergoing the same approach in terms of hormone therapy was selected (N=9, see Methods section for details). P value at peak voxel (P<0.05 whole-brain FWE-corrected at voxel-level) is reported. H=hemisphere, L=left, R=right, FCTR = nulliparous control women who were not pregnant in-between sessions, FPRG_ASS = women who were pregnant in-between sessions and achieved pregnancy by fertility treatment, FPRG_NAT = women who were pregnant in-between session and achieved pregnancy by natural conception.


32

Supplementary Table 19: Changes in GM volume between the PRE and POST sessions: Model excluding participants with complications during pregnancy or delivery

Contrasts


FPRG >

FCTR

-

FCTR >

FPRG



R 57 -18 -11 8.90 <0.001 4356

47 -34 -6 7.44 <0.001

53 -39 -2 7.24 <0.001

L -53 -16 -12 6.20 0.002 726

-56 -33 -6 6.41 0.021

-39 -9 -21 5.63 0.024


L/R 0 -48 30 6.99 <0.001 2083

-8 -57 21 7.17 <0.001

8 -55 22 6.59 0.001



L/R 0 53 13 7.20 <0.001 1910

2 51 -3 6.72 <0.001

-12 54 4 5.65 0.022


L -50 12 16 6.05 0.005 162

-45 8 27 5.48 0.039


Insula

L -39 24 -2 6.36 0.002 192


Fusiform, Inferior Temporal

Gyrus

R 45 -54 -18 5.92 0.009 194

L -41 -52 -14 6.02 0.006 426

Cerebellum R 18 -73 -27 5.56 0.030 12


L -30 -21 -20 5.86 0.010 81

MPRG >

MCTR

-

MCTR >

MPRG

-

Comparisons of GM volume changes across sessions (‘PRE’ and ‘POST’) between the primiparous and nulliparous control groups, extracted from a model excluding the 4 women with complications during pregnancy or delivery (see Methods section for details). P value at peak voxel (P<0.05 whole-brain FWE-corrected) is reported. H=hemisphere, L=left, R=right, FPRG = women who were pregnant and became first-time mothers in-between sessions, FCTR = nulliparous control women who were not pregnant in-between sessions, MPRG = men whose partners were pregnant and who became first-time fathers in-between sessions, MCTR = nulliparous control men whose partners were not pregnant in-between sessions.


33

Supplementary Table 20. Increases and decreases in GM volume in primiparous women: Model including covariates for the method of conception, type of delivery, breastfeeding status and number of fetuses

Contrasts


FPRG

increases

- -

FPRG

decreases


R 59 -18 -11 10.57 0.002 1809

53 -34 -2 9.87 0.005

L -53 -16 -11 9.43 0.009 10

-56 -31 -8 8.59 0.025


L/R 2 -48 31 12.05 <0.001 3581

-2 -24 40 9.80 0.006

5 -15 33 8.57 0.025


L/R 8 54 -3 10.36 0.003 1331

0 57 10 9.78 0.006

0 33 22 8.91 0.017 176

0 20 33 8.61 0.024

Inferior Frontal Cortex, Precentral

Gyrus

R 42 9 28 10.31 0.003 738

Inferior/Middle/Superior Frontal

Cortex, Orbitofrontal Cortex, Insula

L -41 44 3 12.70 <0.001 6676

-21 35 43 12.35 <0.001

-48 20 22 11.89 0.001

Inferior Orbitofrontal Cortex R 35 36 -20 8.81 0.019 86

Fusiform, Inferior Temporal Gyrus, Parahippocampal Gyrus

R 29 -45 -9 9.95 0.005 233

Hippocampus, Parahippocampal Gyus, Fusiform, Amygdala

L -23 -24 -20 9.88 0.005 263

-33 -21 -17 9.57 0.007

-20 3 -26 9.46 0.008 56

Changes in GM volume across sessions (‘PRE’ and ‘POST’) for the women who were pregnant in-between sessions, extracted from a model including covariates for the method of conception, the type of delivery, the number of fetuses (1 or 2) and breastfeeding status (see Methods section for more details). P value at peak voxel (P<0.05 whole-brain FWE-corrected at voxel-level) is reported. H=hemisphere, L=left, R=right, FPRG = women who were pregnant and transitioned to primiparity in-between sessions.


34

Supplementary Table 21: Changes in GM volume between the PRE and POST sessions: Model excluding the woman who developed postpartum depression

Contrasts


FPRG >

FCTR

- -

FCTR >

FPRG


Middle/Superior Temporal Gyrus/Parahippocampal Gyrus

R 57 -18 -11 8.65 <0.001 2807

51 -31 -6 6.84 <0.001

33 -37 -14 6.72 <0.001 507

33 -25 -18 6.01 0.006

L -54 -18 -11 6.20 0.003 527

-56 -33 -6 5.88 0.010


L/R 0 -48 30 7.42 <0.001 2274

-6 -57 21 7.23 <0.001

8 -55 22 6.75 <0.001


L/R 0 51 12 6.99 <0.001 1169

-12 54 4 5.96 0.007

0 48 -6 5.77 0.015


L -50 12 16 5.63 0.024 23

Inferior Orbitofrontal Gyrus, Inferior Frontal Gyrus, Insula

L -39 24 -2 6.34 0.002 192



R 45 -54 -18 5.59 0.028 32

L -44 -54 -14 6.25 0.003 462


L -32 -21 -18 5.85 0.011 71

MPRG >

MCTR

-

MCTR >

MPRG

-

Comparisons of GM volume changes across sessions (‘PRE’ and ‘POST’) between the primiparous and nulliparous control groups, extracted from a model excluding the woman who developed clinical postpartum depression. P value at peak voxel (P<0.05 whole-brain FWE-corrected) is reported. H=hemisphere, L=left, R=right FPRG = women who were pregnant and became first-time mothers in-between sessions, FCTR = nulliparous control women who were not pregnant in-between sessions, MPRG = men whose partners were pregnant and who became first-time fathers in-between sessions, MCTR = nulliparous control men whose partners were not pregnant in-between sessions.


35

Supplementary Table 22: Changes in GM volume between the PRE and POST sessions: Model excluding participants acquired with the other head coil in one of the sessions

Contrasts


FPRG>

FCTR

- -

FCTR >

FPRG


Middle/Superior Temporal Gyrus, Angular Gyrus, Fusiform Gyrus, Parahippocampal Gyrus, Hippocampus, Cerebellum

R 57 -18 -11 8.32 *<0.0001 9345

48 -36 0 5.89 *<0.0001

41 -55 -17 5.72 *<0.0001

45 -52 24 4.79 <0.0001 509

L -53 -15 -11 5.57 <0.0001 3576

-39 -13 -20 5.03 *<0.0001

-57 -34 -3 4.75 <0.0001

-42 -61 25 4.83 <0.0001 630

Precuneus, Posterior Cingulate Cortex, Fusiform Gyrus, Cerebellum

L/R -39 -55 -15 6.16 <0.0001 6743

11 -55 19 5.92 *<0.0001

-8 -58 21 5.81 <0.0001

Superior Medial Frontal Cortex, Anterior Cingulate Cortex, Medial Orbitofrontal Cortex, Inferior/Middle/Superior Frontal Cortex, Insula

L/R -38 36 7 5.72 *<0.0001 11912

-14 54 1 5.46 <0.0001

-50 12 18 5.43 <0.0001

39 15 24 5.23 <0.0001 1583

51 17 16 4.74 <0.0001

36 30 9 4.42 <0.0001 180

27 30 45 4.25 <0.0001 52

-8 54 42 4.20 <0.0001 176

Amygdala L -26 0 -23 4.16 <0.0001 31

MPRG>

MCTR

-

MCTR >

MPRG

-

Comparisons of GM volume changes across sessions (‘PRE’ and ‘POST’) between the primiparous and nulliparous control groups, extracted from a model excluding the 28 participants for whom another head coil was used during one of the sessions (see Methods for details). Considering the reduced number of subjects available for this analysis, the results were inspected at the more lenient threshold of p<0.0001. The clusters also surfacing at the P<0.05 FWE-corrected threshold are indicated with an asterisk. H=hemisphere, L=left, R=right, FPRG = women who were pregnant and became first-time mothers in-between sessions, FCTR = nulliparous control women who were not pregnant in-between sessions, MPRG = men whose partners were pregnant and who became first-time fathers in-between sessions, MCTR = nulliparous control men whose partners were not pregnant in-between sessions.


36

Supplementary Table 23. Neural activity in response to baby facial expressions

Contrasts


sad>neutral

Middle/Superior Occipital Cortex R 30 -72 4 6.62 *<0.0001 239

26 -82 16 5.85 <0.0001

38 -86 6 5.61 <0.0001

Middle/Superior Occipital Cortex L -26 -80 20 5.89 <0.0001 66

neutral>sad -

(own baby

sad>neutral) > (other baby sad>neutral)

-

(other baby

sad>neutral) > (own baby sad>neutral)

-

Neural activity of primiparous mothers (N=20) in response to pictures of babies with a sad facial expression (crying) in comparison to a neutral facial expression in the postpartum fMRI paradigm. The bottom two rows indicate the interaction contrasts involving the facial expression of the baby and the “own” vs. “other” factor (whether the baby in the picture represented the women’s own infant or another unknown infant). P value at peak voxel is reported. The clusters that are significant at the threshold of P<0.05 FWE-corrected are indicated, but, for exploratory purposes, the results were also examined at the more lenient threshold of p<0.0001. * P<0.05 FWE-corrected. H=hemisphere, L=left, R=right.


Nature Neuroscience: doi:10.1038/nnL/R 0 -48 30 6.66 0.001 1162 -8 -57 21 6.53 0.001 8 -55 22 6.07...

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