Brain health in diverse settings: How age, demographics and cognition shape brain function.

Diversity in brain health is influenced by individual differences in demographics and cognition. However, most studies on brain health and diseases have typically controlled for these factors rather than explored their potential to predict brain signals. Here, we assessed the role of individual differences in demographics (age, sex, and education; n = 1298) and cognition (n = 725) as predictors of different metrics usually used in case-control studies. These included power spectrum and aperiodic (1/f slope, knee, offset) metrics, as well as complexity (fractal dimension estimation, permutation entropy, Wiener entropy, spectral structure variability) and connectivity (graph-theoretic mutual information, conditional mutual information, organizational information) from the source space resting-state EEG activity in a diverse sample from the global south and north populations. Brain-phenotype models were computed using EEG metrics reflecting local activity (power spectrum and aperiodic components) and brain dynamics and interactions (complexity and graph-theoretic measures). Electrophysiological brain dynamics were modulated by individual differences despite the varied methods of data acquisition and assessments across multiple centers, indicating that results were unlikely to be accounted for by methodological discrepancies. Variations in brain signals were mainly influenced by age and cognition, while education and sex exhibited less importance. Power spectrum activity and graph-theoretic measures were the most sensitive in capturing individual differences. Older age, poorer cognition, and being male were associated with reduced alpha power, whereas older age and less education were associated with reduced network integration and segregation. Findings suggest that basic individual differences impact core metrics of brain function that are used in standard case-control studies. Considering individual variability and diversity in global settings would contribute to a more tailored understanding of brain function.

Addition of rapamycin or co-culture with cumulus cells from younger reproductive age women does not improve rescue in vitro oocyte maturation or euploidy rates in older reproductive age women.

Both spontaneously conceived pregnancies and those achieved using assisted reproduction decline with advancing maternal age. In this study, we tested if rapamycin and/or cumulus cells (CCs) from young donors could improve oocyte maturation and euploidy rates of germinal vesicle (GV) stage oocytes obtained from older women of reproductive age. A total of 498 GVs from 201 women >38 years (40.6 ± 1.8, mean ± SD) were included. GVs were randomly assigned into five groups for rescue IVM: control (with no CCs and no rapamycin); with autologous CCs; with autologous CCs and rapamycin; with CCs from young women (<35 years); and with CCs from young women and rapamycin. After 24 h of culture, the first polar body (PB) was biopsied in metaphase II oocytes, and the cytogenetic constitution was assessed using next-generation sequencing for both oocytes and PBs. Comparable maturation rates were found (56.2%, 60.0%, 46.5%, 51.7%, and 48.5% for groups 1-5, respectively; P = 0.30). Similarly, comparable euploidy rates were observed in the five groups (41.5%, 37.8%, 47.2%, 43.6%, and 47.8% for Groups 1-5, respectively; P = 0.87). Our findings indicate that rescue IVM is effective for obtaining mature euploid oocytes in older women of reproductive age, and that incubation with rapamycin or CCs obtained from young donors does not improve the maturation or euploidy rate.

Preimplantation genetic testing for aneuploidy: predictive embryonic factors.

PURPOSE: In a preimplantation genetic testing for aneuploidy (PGT-A) cycle, does the blastocyst quality before biopsy, or the day of biopsy, or the embryo hatching status have an impact on either euploidy or the rate of embryo survival after freezing? METHODS: This was a retrospective study including 6130 biopsied blastocysts coming from 1849 PGT-A cycles performed in our center (2016-2022). Embryos were categorized according to the inner cell mass and trophectoderm quality, using Gardner's scoring (excellent: AA; good: AB, BA, BB; poor: AC, CA, BC, CB, CC); the day of biopsy (5 or 6); and their hatching status (fully hatched blastocysts [FHB] or non-fully hatched blastocysts [nFHB]). The independent relationship between each group and both euploidy and survival rate was assessed. RESULTS: Excellent-quality embryos were more euploid than both good- and poor-quality embryos (52.69%, 39.69%, and 26.21%; p < 0.001), and day 5-biopsied embryos were more euploid than day 6-biopsied embryos (39.98% and 34.80%; p < 0.001). Survival rates of excellent-quality (92.26%) and good-quality (92.47%) embryos were higher than survival rates in the poor-quality group (84.61%) (p = 0.011 and p = 0.002). Day 5-biopsied embryos survived better than day 6-biopsied embryos (93.71% vs. 83.69%; p < 0.001) and FHB had poorer survival than nFHB (78.61% vs. 93.52%; p < 0.001). CONCLUSIONS: Excellent-quality and day 5-biopsied embryos are more prone to be euploid than good and poor or day 6-biopsied embryos, respectively. Poor-quality, day 6-biopsied embryos, and FHB have significantly lower survival after biopsy and vitrification.

Viscous dynamics associated with hypoexcitation and structural disintegration in neurodegeneration via generative whole-brain modeling.

INTRODUCTION: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) lack mechanistic biophysical modeling in diverse, underrepresented populations. Electroencephalography (EEG) is a high temporal resolution, cost-effective technique for studying dementia globally, but lacks mechanistic models and produces non-replicable results. METHODS: We developed a generative whole-brain model that combines EEG source-level metaconnectivity, anatomical priors, and a perturbational approach. This model was applied to Global South participants (AD, bvFTD, and healthy controls). RESULTS: Metaconnectivity outperformed pairwise connectivity and revealed more viscous dynamics in patients, with altered metaconnectivity patterns associated with multimodal disease presentation. The biophysical model showed that connectome disintegration and hypoexcitability triggered altered metaconnectivity dynamics and identified critical regions for brain stimulation. We replicated the main results in a second subset of participants for validation with unharmonized, heterogeneous recording settings. DISCUSSION: The results provide a novel agenda for developing mechanistic model-inspired characterization and therapies in clinical, translational, and computational neuroscience settings.

Source space connectomics of neurodegeneration: One-metric approach does not fit all.

Brain functional connectivity in dementia has been assessed with dissimilar EEG connectivity metrics and estimation procedures, thereby increasing results' heterogeneity. In this scenario, joint analyses integrating information from different metrics may allow for a more comprehensive characterization of brain functional interactions in different dementia subtypes. To test this hypothesis, resting-state electroencephalogram (rsEEG) was recorded in individuals with Alzheimer's Disease (AD), behavioral variant frontotemporal dementia (bvFTD), and healthy controls (HCs). Whole-brain functional connectivity was estimated in the EEG source space using 101 different types of functional connectivity, capturing linear and nonlinear interactions in both time and frequency-domains. Multivariate machine learning and progressive feature elimination was run to discriminate AD from HCs, and bvFTD from HCs, based on joint analyses of i) EEG frequency bands, ii) complementary frequency-domain metrics (e.g., instantaneous, lagged, and total connectivity), and iii) time-domain metrics with different linearity assumption (e.g., Pearson correlation coefficient and mutual information). <10% of all possible connections were responsible for the differences between patients and controls, and atypical connectivity was never captured by >1/4 of all possible connectivity measures. Joint analyses revealed patterns of hypoconnectivity (patientsHCs) in both groups was mainly identified in frontotemporal regions. These atypicalities were differently captured by frequency- and time-domain connectivity metrics, in a bandwidth-specific fashion. The multi-metric representation of source space whole-brain functional connectivity evidenced the inadequacy of single-metric approaches, and resulted in a valid alternative for the selection problem in EEG connectivity. These joint analyses reveal patterns of brain functional interdependence that are overlooked with single metrics approaches, contributing to a more reliable and interpretable description of atypical functional connectivity in neurodegeneration.

Calcium Ionophore A23187 treatment to rescue unfertilized oocytes: a prospective randomized analysis of sibling oocytes.

RESEARCH QUESTION: Can 1-day old human unfertilized oocytes activate and blastulate after exposure to calcium ionophore (Ca.I) A23187? DESIGN: Prospective randomized trial analysis of sibling oocytes. Seventy unfertilized sibling oocytes from 24 couples were randomly split into two groups. In the treatment group, 35 oocytes were cultured with 5-µM Ca.I A23187 for 10 min, washed and cultured until day 6 of development (D+6). The remaining 35 oocytes (control group) were similarly cultured until D+6. Activation, cleavage and blastulation rates were compared between the two groups. RESULTS: Comparable activation rates were observed in the oocytes incubated with Ca.I A23187 and in the control group (11.4% versus 17.1%; P = 0.49). The cleavage rate observed was 45.7% in both groups. None of the embryos reached blastocyst stage. CONCLUSIONS: Activation and cleavage can occur in unfertilized oocytes after the diagnosis of failure to fertilize. Unfortunately, the prevalence of activation is not affected by exposure to Ca.I A23187. Additionally, these embryos have no tangible reproductive potential as they arrest before reaching the blastocyst stage.

External validation of putative biomarkers in eutopic endometrium of women with endometriosis using NanoString technology.

PURPOSE: To combine different independent endometrial markers to classify the presence of endometriosis. METHODS: Endometrial biopsies were obtained from 109 women with endometriosis as well as 110 control women. Nine candidate biomarkers independent of cycle phase were selected from the literature and NanoString was performed. We compared differentially expressed genes between groups and generated generalized linear models to find a classifier for the disease. RESULTS: Generalized linear models correctly detected 68% of women with endometriosis (combining deep infiltrating and ovarian endometriosis). However, we were not able to distinguish between individual types of endometriosis compared to controls. From the 9 tested genes, FOS, MMP7, and MMP11 seem to be important for disease classification, and FOS was the most over-expressed gene in endometriosis. CONCLUSION(S): Although generalized linear models may allow identification of endometriosis, we did not obtain perfect classification with the selected gene candidates.

Pregnancy and adolescence entail similar neuroanatomical adaptations: A comparative analysis of cerebral morphometric changes.

Mapping the impact of pregnancy on the human brain is essential for understanding the neurobiology of maternal caregiving. Recently, we found that pregnancy leads to a long-lasting reduction in cerebral gray matter volume. However, the morphometric features behind the volumetric reductions remain unexplored. Furthermore, the similarity between these reductions and those occurring during adolescence, another hormonally similar transitional period of life, still needs to be investigated. Here, we used surface-based methods to analyze the longitudinal magnetic resonance imaging data of a group of 25 first-time mothers (before and after pregnancy) and compare them to those of a group of 25 female adolescents (during 2 years of pubertal development). For both first-time mothers and adolescent girls, a monthly rate of volumetric reductions of 0.09 mm3 was observed. In both cases, these reductions were accompanied by decreases in cortical thickness, surface area, local gyrification index, sulcal depth, and sulcal length, as well as increases in sulcal width. In fact, the changes associated with pregnancy did not differ from those that characterize the transition during adolescence in any of these measures. Our findings are consistent with the notion that the brain morphometric changes associated with pregnancy and adolescence reflect similar hormonally primed biological processes.

Endometrial Stromal Cells Circulate in the Bloodstream of Women with Endometriosis: A Pilot Study.

Endometriosis is characterized by the presence of endometrial tissue outside the uterus. While endometriotic tissue is commonly localized in the pelvic cavity, it can also be found in distant sites, including the brain. The origin and pathophysiology of tissue migration is poorly understood; retrograde menstruation is thought to be the cause, although the presence of endometrium at distant sites is not explained by this hypothesis. To determine whether dissemination occurs via the bloodstream in women with endometriosis, we analyzed circulating blood for the presence of endometrial cells. Circulating endometrial stromal cells were identified only in women with endometriosis but not in controls, while endometrial epithelial cells were not identified in the circulation of either group. Our results support the hypothesis that endometrial stromal cells may migrate through circulation and promote the pathophysiology of endometriosis. The detection of these cells in circulation creates avenues for the development of less invasive diagnostic tools for the disease, and opens possibilities for further study of the origin of endometriosis.

Lgr5 Does Not Vary Throughout the Menstrual Cycle in Endometriotic Human Eutopic Endometrium.

Endometriosis is characterized by the abnormal presence of endometrium outside of the uterus, resulting in pelvic pain and infertility. The leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) has been postulated to be a marker of stem cells in the endometrium. However, LGR5⁺ cells have a macrophage-like phenotype in this tissue, so it is unclear what role LGR5⁺ cells actually play in the endometrium. Macrophages serve an important function in the endometrium to maintain fertility, while LGR5⁺ cells generally have a role in tumor progression and are involved in invasion in some cancers. We sought to determine whether LGR5⁺ cells vary across the menstrual cycle in women with endometriosis and whether there are implications for LGR5 in the aggressiveness of endometriosis and reproductive outcomes. We performed immunofluorescence, flow cytometry, and primary culture in vitro experiments on eutopic and ectopic endometrium from healthy and endometriosis patients and observed that neither LGR5⁺ cells nor LGR5 expression varied throughout the cycle. Interestingly, we observed that LGR5⁺ cell percentage overexpressing CD163 (anti-inflammatory marker) was higher in healthy endometrium, suggesting that in endometriosis, endometrium presents a more pro-inflammatory phenotype that likely leads to poor obstetric outcomes. We also observed higher levels of LGR5⁺ cells in ectopic lesions compared to eutopic endometrium and specifically in deep infiltrating endometriosis, indicating that LGR5 could be involved in progression and aggressiveness of the disease.

Neuroanatomical markers of social cognition in neglected adolescents.

Growing up in neglectful households can impact multiple aspects of social cognition. However, research on neglect's effects on social cognition processes and their neuroanatomical correlates during adolescence is scarce. Here, we aimed to comprehensively assess social cognition processes (recognition of basic and contextual emotions, theory of mind, the experience of envy and Schadenfreude and empathy for pain) and their structural brain correlates in adolescents with legal neglect records within family-based care. First, we compared neglected adolescents (n = 27) with control participants (n = 25) on context-sensitive social cognition tasks while controlling for physical and emotional abuse and executive and intellectual functioning. Additionally, we explored the grey matter correlates of these domains through voxel-based morphometry. Compared to controls, neglected adolescents exhibited lower performance in contextual emotional recognition and theory of mind, higher levels of envy and Schadenfreude and diminished empathy. Physical and emotional abuse and executive or intellectual functioning did not explain these effects. Moreover, social cognition scores correlated with brain volumes in regions subserving social cognition and emotional processing. Our results underscore the potential impact of neglect on different aspects of social cognition during adolescence, emphasizing the necessity for preventive and intervention strategies to address these deficits in this population.

Brain clocks capture diversity and disparity in aging and dementia.

Brain clocks, which quantify discrepancies between brain age and chronological age, hold promise for understanding brain health and disease. However, the impact of multimodal diversity (geographical, socioeconomic, sociodemographic, sex, neurodegeneration) on the brain age gap (BAG) is unknown. Here, we analyzed datasets from 5,306 participants across 15 countries (7 Latin American countries -LAC, 8 non-LAC). Based on higher-order interactions in brain signals, we developed a BAG deep learning architecture for functional magnetic resonance imaging (fMRI=2,953) and electroencephalography (EEG=2,353). The datasets comprised healthy controls, and individuals with mild cognitive impairment, Alzheimer's disease, and behavioral variant frontotemporal dementia. LAC models evidenced older brain ages (fMRI: MDE=5.60, RMSE=11.91; EEG: MDE=5.34, RMSE=9.82) compared to non-LAC, associated with frontoposterior networks. Structural socioeconomic inequality and other disparity-related factors (pollution, health disparities) were influential predictors of increased brain age gaps, especially in LAC (R2=0.37, F2=0.59, RMSE=6.9). A gradient of increasing BAG from controls to mild cognitive impairment to Alzheimer's disease was found. In LAC, we observed larger BAGs in females in control and Alzheimer's disease groups compared to respective males. Results were not explained by variations in signal quality, demographics, or acquisition methods. Findings provide a quantitative framework capturing the multimodal diversity of accelerated brain aging.

Brain clocks capture diversity and disparities in aging and dementia across geographically diverse populations.

Brain clocks, which quantify discrepancies between brain age and chronological age, hold promise for understanding brain health and disease. However, the impact of diversity (including geographical, socioeconomic, sociodemographic, sex and neurodegeneration) on the brain-age gap is unknown. We analyzed datasets from 5,306 participants across 15 countries (7 Latin American and Caribbean countries (LAC) and 8 non-LAC countries). Based on higher-order interactions, we developed a brain-age gap deep learning architecture for functional magnetic resonance imaging (2,953) and electroencephalography (2,353). The datasets comprised healthy controls and individuals with mild cognitive impairment, Alzheimer disease and behavioral variant frontotemporal dementia. LAC models evidenced older brain ages (functional magnetic resonance imaging: mean directional error = 5.60, root mean square error (r.m.s.e.) = 11.91; electroencephalography: mean directional error = 5.34, r.m.s.e. = 9.82) associated with frontoposterior networks compared with non-LAC models. Structural socioeconomic inequality, pollution and health disparities were influential predictors of increased brain-age gaps, especially in LAC (R² = 0.37, F² = 0.59, r.m.s.e. = 6.9). An ascending brain-age gap from healthy controls to mild cognitive impairment to Alzheimer disease was found. In LAC, we observed larger brain-age gaps in females in control and Alzheimer disease groups compared with the respective males. The results were not explained by variations in signal quality, demographics or acquisition methods. These findings provide a quantitative framework capturing the diversity of accelerated brain aging.

Evaluation of the degree of satisfaction in oocyte donors using sustained-release FSH corifollitropin α.

Ovarian stimulation treatment is recognized as placing a physical and psychological burden on patients and oocyte donors. The introduction of sustained follicle stimulants will reduce the number of injections and may improve the overall patient experience. This study aimed to evaluate the degree of satisfaction in oocyte donors undergoing treatment with corifollitropin α, a synthetic recombinant rFSH which replaces daily FSH injections for the first week of ovarian stimulation. The results showed no significant differences in clinical parameters between the two protocols (recombinant FSH versus corifollitropin α). Implantation rates for the corifollitropin α and daily FSH protocol groups were 39.1% and 38.4%, respectively, while ongoing pregnancy rates were 45.9% and 44.4%. There were no statistical between-group differences in the responses to the questionnaires. However, donors treated with corifollitropin α who had undergone a previous cycle with daily FSH reported greater satisfaction with the corifollitropin α protocol. In conclusion, no significant differences were found in any analysed parameters between treatments. However, when donors who had undergone both treatments chose which treatment they preferred, the results clearly showed a positive trend towards choosing corifollitropin α, confirming that this protocol may reduce treatment burden and increase donor compliance.

Harmonized multi-metric and multi-centric assessment of EEG source space connectivity for dementia characterization.

Introduction: Harmonization protocols that address batch effects and cross-site methodological differences in multi-center studies are critical for strengthening electroencephalography (EEG) signatures of functional connectivity (FC) as potential dementia biomarkers. Methods: We implemented an automatic processing pipeline incorporating electrode layout integrations, patient-control normalizations, and multi-metric EEG source space connectomics analyses. Results: Spline interpolations of EEG signals onto a head mesh model with 6067 virtual electrodes resulted in an effective method for integrating electrode layouts. Z-score transformations of EEG time series resulted in source space connectivity matrices with high bilateral symmetry, reinforced long-range connections, and diminished short-range functional interactions. A composite FC metric allowed for accurate multicentric classifications of Alzheimer's disease and behavioral variant frontotemporal dementia. Discussion: Harmonized multi-metric analysis of EEG source space connectivity can address data heterogeneities in multi-centric studies, representing a powerful tool for accurately characterizing dementia.

Factors associated with healthy aging in Latin American populations.

Latin American populations may present patterns of sociodemographic, ethnic and cultural diversity that can defy current universal models of healthy aging. The potential combination of risk factors that influence aging across populations in Latin American and Caribbean (LAC) countries is unknown. Compared to other regions where classical factors such as age and sex drive healthy aging, higher disparity-related factors and between-country variability could influence healthy aging in LAC countries. We investigated the combined impact of social determinants of health (SDH), lifestyle factors, cardiometabolic factors, mental health symptoms and demographics (age, sex) on healthy aging (cognition and functional ability) across LAC countries with different levels of socioeconomic development using cross-sectional and longitudinal machine learning models (n = 44,394 participants). Risk factors associated with social and health disparities, including SDH (ß > 0.3), mental health (ß > 0.6) and cardiometabolic risks (ß > 0.22), significantly influenced healthy aging more than age and sex (with null or smaller effects: ß < 0.2). These heterogeneous patterns were more pronounced in low-income to middle-income LAC countries compared to high-income LAC countries (cross-sectional comparisons), and in an upper-income to middle-income LAC country, Costa Rica, compared to China, a non-upper-income to middle-income LAC country (longitudinal comparisons). These inequity-associated and region-specific patterns inform national risk assessments of healthy aging in LAC countries and regionally tailored public health interventions.

The BrainLat project, a multimodal neuroimaging dataset of neurodegeneration from underrepresented backgrounds.

The Latin American Brain Health Institute (BrainLat) has released a unique multimodal neuroimaging dataset of 780 participants from Latin American. The dataset includes 530 patients with neurodegenerative diseases such as Alzheimer's disease (AD), behavioral variant frontotemporal dementia (bvFTD), multiple sclerosis (MS), Parkinson's disease (PD), and 250 healthy controls (HCs). This dataset (62.7 ± 9.5 years, age range 21-89 years) was collected through a multicentric effort across five Latin American countries to address the need for affordable, scalable, and available biomarkers in regions with larger inequities. The BrainLat is the first regional collection of clinical and cognitive assessments, anatomical magnetic resonance imaging (MRI), resting-state functional MRI (fMRI), diffusion-weighted MRI (DWI), and high density resting-state electroencephalography (EEG) in dementia patients. In addition, it includes demographic information about harmonized recruitment and assessment protocols. The dataset is publicly available to encourage further research and development of tools and health applications for neurodegeneration based on multimodal neuroimaging, promoting the assessment of regional variability and inclusion of underrepresented participants in research.

Allostatic-Interoceptive Overload in Frontotemporal Dementia.

BACKGROUND: The predictive coding theory of allostatic-interoceptive load states that brain networks mediating autonomic regulation and interoceptive-exteroceptive balance regulate the internal milieu to anticipate future needs and environmental demands. These functions seem to be distinctly compromised in behavioral variant frontotemporal dementia (bvFTD), including alterations of the allostatic-interoceptive network (AIN). Here, we hypothesize that bvFTD is typified by an allostatic-interoceptive overload. METHODS: We assessed resting-state heartbeat evoked potential (rsHEP) modulation as well as its behavioral and multimodal neuroimaging correlates in patients with bvFTD relative to healthy control subjects and patients with Alzheimer's disease (N = 94). We measured 1) resting-state electroencephalography (to assess the rsHEP, prompted by visceral inputs and modulated by internal body sensing), 2) associations between rsHEP and its neural generators (source location), 3) cognitive disturbances (cognitive state, executive functions, facial emotion recognition), 4) brain atrophy, and 5) resting-state functional magnetic resonance imaging functional connectivity (AIN vs. control networks). RESULTS: Relative to healthy control subjects and patients with Alzheimer's disease, patients with bvFTD presented more negative rsHEP amplitudes with sources in critical hubs of the AIN (insula, amygdala, somatosensory cortex, hippocampus, anterior cingulate cortex). This exacerbated rsHEP modulation selectively predicted the patients' cognitive profile (including cognitive decline, executive dysfunction, and emotional impairments). In addition, increased rsHEP modulation in bvFTD was associated with decreased brain volume and connectivity of the AIN. Machine learning results confirmed AIN specificity in predicting the bvFTD group. CONCLUSIONS: Altogether, these results suggest that bvFTD may be characterized by an allostatic-interoceptive overload manifested in ongoing electrophysiological markers, brain atrophy, functional networks, and cognition.

Impact of sperm DNA fragmentation on the outcome of IVF with own or donated oocytes.

A prospective study was performed to assess the impact of sperm DNA fragmentation on the outcome of IVF with own or donated oocytes. The study population included 178 couples (62 cycles of IVF, 116 of intracytoplasmic sperm injection (ICSI)) with own (n=77) and donor (n=101) oocytes. DNA fragmentation was evaluated by TdT (terminal deoxynucleotidyl transferase)-mediated dUDP nick-end labelling assay. Correlation between DNA damage to oocyte fertilization, embryo quality and clinical pregnancy, implantation and miscarriage rates was evaluated. DNA fragmentation was not related to fertilization rates in either IVF (r=0.08) or ICSI (r=-0.04) cycles. DNA fragmentation was similar in patients with <50% embryo utilization rate compared with ≥50%, in cancelled and in embryo transfer cycles and in miscarriages and in successful deliveries. Moreover, DNA fragmentation was similar in pregnant and non-pregnant women as well as in IVF with own or donor oocytes. In the multivariable analysis, the odds ratio of DNA after controlling by age was 1.0. Using a 36% sperm fragmentation threshold, results did not vary. It is concluded that DNA damage was not related to outcomes of IVF or ICSI with own or donor oocytes.

Do Pregnancy-Induced Brain Changes Reverse? The Brain of a Mother Six Years after Parturition.

Neuroimaging researchers commonly assume that the brain of a mother is comparable to that of a nulliparous woman. However, pregnancy leads to pronounced gray matter volume reductions in the mother's brain, which have been associated with maternal attachment towards the baby. Beyond two years postpartum, no study has explored whether these brain changes are maintained or instead return to pre-pregnancy levels. The present study tested whether gray matter volume reductions detected in primiparous women are still present six years after parturition. Using data from a unique, prospective neuroimaging study, we compared the gray matter volume of 25 primiparous and 22 nulliparous women across three sessions: before conception (n = 25/22), during the first months of postpartum (n = 25/21), and at six years after parturition (n = 7/5). We found that most of the pregnancy-induced gray matter volume reductions persist six years after parturition (classifying women as having been pregnant or not with 91.67% of total accuracy). We also found that brain changes at six years postpartum are associated with measures of mother-to-infant attachment. These findings open the possibility that pregnancy-induced brain changes are permanent and encourage neuroimaging studies to routinely include pregnancy-related information as a relevant demographic variable.