Previous pregnancies might mitigate cortical brain differences associated with surgical menopause.

Surgical menopause causes a sharp drop in estrogen levels in middle-aged women, thus preventing the gradual physiological adaptation that is characteristic of the perimenopause. Previous studies suggest that surgical menopause might increase the risk of dementia later in life. In addition, the transition to motherhood entails long-lasting endocrine and neuronal adaptations. We compared differences in whole-brain cortical volume between women who reached menopause by surgery and a group of women who reached spontaneous non-surgical menopause and determined whether these cortical differences were influenced by previous childbearing. Using surface-based neuroimaging techniques, we investigated cortical volume differences in 201 middle-aged women (134 women who experienced non-surgical menopause, 78 of whom were parous women; and 67 women who experienced surgical menopause, 39 of whom were parous women). We found significant atrophy in the frontal and temporal regions in women who experienced surgical menopause. Nulliparous women with surgical menopause showed significant lower cortical volume in the left temporal gyrus extending to the medial temporal lobe cortex, as well as in the precuneus bilaterally compared to parous women with surgical menopause; whereas our results revealed no significant differences between parous women with surgical menopause and both parous and nulliparous women who reached a non-surgical menopause. Furthermore, in the surgical menopause group, we found a negative correlation between cortical volume and age at first pregnancy in the temporal lobe. Our study suggests that the long-term brain remodeling of parity may mitigate the neural impact of the sudden drop in estrogen levels that characterizes surgical menopause.

Changes in left hippocampal volume in first-time fathers: Associations with oxytocin, testosterone, and adaptation to parenthood.

The parenting brain may undergo remodeling that supports the adjustment to new parenthood. Prior work on human mothers has found gray matter volume decreases from preconception to early postpartum in multiple structures, including the left hippocampus, which was the only structure to show gray matter volume recovery at 2 years postpartum. This is consistent with evidence from animal models that the hippocampus is unusually plastic across reproductive transitions. However, no studies have focused specifically on hippocampal volume changes in human fathers. Among 38 men who were scanned by magnetic resonance imaging (MRI) before and after having their first child, individual differences in left hippocampal volume changes were associated with men's prenatal oxytocin, postpartum testosterone, and postpartum adaptation to parenthood. Across the whole sample, hippocampal volumes did not change significantly from prenatal to postpartum. However, men who showed larger increases in left hippocampal volume from prenatal to postpartum reported stronger parent-child bonding and affectionate attachment and lower parenting stress. Fathers with higher levels of prenatal oxytocin showed larger left hippocampal volume increases across the transition to parenthood. In turn, greater increases in left hippocampal volume predicted lower postpartum testosterone after adjusting for prenatal testosterone. These findings did not extend to the right hippocampus. In conclusion, remodeling of the left hippocampus across the transition to new fatherhood may reflect adaptation to parenthood in human males.

First-time fathers show longitudinal gray matter cortical volume reductions: evidence from two international samples.

Emerging evidence points to the transition to parenthood as a critical window for adult neural plasticity. Studying fathers offers a unique opportunity to explore how parenting experience can shape the human brain when pregnancy is not directly experienced. Yet very few studies have examined the neuroanatomic adaptations of men transitioning into fatherhood. The present study reports on an international collaboration between two laboratories, one in Spain and the other in California (United States), that have prospectively collected structural neuroimaging data in 20 expectant fathers before and after the birth of their first child. The Spanish sample also included a control group of 17 childless men. We tested whether the transition into fatherhood entailed anatomical changes in brain cortical volume, thickness, and area, and subcortical volumes. We found overlapping trends of cortical volume reductions within the default mode network and visual networks and preservation of subcortical structures across both samples of first-time fathers, which persisted after controlling for fathers' and children's age at the postnatal scan. This study provides convergent evidence for cortical structural changes in fathers, supporting the possibility that the transition to fatherhood may represent a meaningful window of experience-induced structural neuroplasticity in males.

ABLE: Automated Brain Lines Extraction Based on Laplacian Surface Collapse.

The archetypical folded shape of the human cortex has been a long-standing topic for neuroscientific research. Nevertheless, the accurate neuroanatomical segmentation of sulci remains a challenge. Part of the problem is the uncertainty of where a sulcus transitions into a gyrus and vice versa. This problem can be avoided by focusing on sulcal fundi and gyral crowns, which represent the topological opposites of cortical folding. We present Automated Brain Lines Extraction (ABLE), a method based on Laplacian surface collapse to reliably segment sulcal fundi and gyral crown lines. ABLE is built to work on standard FreeSurfer outputs and eludes the delineation of anastomotic sulci while maintaining sulcal fundi lines that traverse the regions with the highest depth and curvature. First, it segments the cortex into gyral and sulcal surfaces; then, each surface is spatially filtered. A Laplacian-collapse-based algorithm is applied to obtain a thinned representation of the surfaces. This surface is then used for careful detection of the endpoints of the lines. Finally, sulcal fundi and gyral crown lines are obtained by eroding the surfaces while preserving the connectivity between the endpoints. The method is validated by comparing ABLE with three other sulcal extraction methods using the Human Connectome Project (HCP) test-retest database to assess the reproducibility of the different tools. The results confirm ABLE as a reliable method for obtaining sulcal lines with an accurate representation of the sulcal topology while ignoring anastomotic branches and the overestimation of the sulcal fundi lines. ABLE is publicly available via https://github.com/HGGM-LIM/ABLE .

Recent Neuroscience Advances in Human Parenting.

The transition to parenthood entails brain adaptations to the demands of caring for a newborn. This chapter reviews recent neuroscience findings on human parenting, focusing on neuroimaging studies. First, we describe the brain circuits underlying human maternal behavior, which comprise ancient subcortical circuits and more sophisticated cortical regions. Then, we present the short-term and long-term functional and structural brain adaptations that characterize the transition to motherhood, discuss the long-term effects of parenthood on the brain, and propose several underlying neural mechanisms. We also review neuroimaging findings in biological fathers and alloparents (such as other relatives or adoptive parents), who engage in parenting without directly experiencing pregnancy or childbirth. Finally, we describe perinatal mental illnesses and discuss the neural responses associated with such disorders. To date, studies indicate that parenthood is a period of enhanced brain plasticity within brain areas critical for cognitive and social processing and that both parenting experience and gestational-related factors can prime such plasticity.

Local Functional Connectivity as a Parsimonious Explanation of the Main Frameworks for ADHD in Medication-Naïve Adults.

OBJECTIVE: Neuroimaging studies in children with ADHD indicate that their brain exhibits an atypical functional connectivity pattern characterized by increased local connectivity and decreased distant connectivity. We aim to evaluate if the local and distant distribution of functional connectivity is also altered in adult samples with ADHD who have never received medication before. METHODS: We compared local and distant functional connectivity between 31 medication-naïve adults with ADHD and 31 healthy controls and tested whether this pattern was associated with symptoms severity scores. RESULTS: ADHD sample showed increased local connectivity in the dACC and the SFG and decreased local connectivity in the PCC. CONCLUSION: Results parallel those obtained in children samples suggesting a deficient integration within the DMN and segregation between DMN, FPN, and VAN. These results are consistent with the three main frameworks that explain ADHD: the neurodevelopmental delay hypothesis, the DMN interference hypothesis and multi-network models.

Local Functional Connectivity as a Parsimonious Explanation of the Main Frameworks for ADHD in Medication-Naïve Adults.

Objective: Neuroimaging studies in children with ADHD indicate that their brain exhibits an atypical functional connectivity pattern characterized by increased local connectivity and decreased distant connectivity. We aim to evaluate if the local and distant distribution of functional connectivity is also altered in adult samples with ADHD who have never received medication before. Methods: We compared local and distant functional connectivity between 31 medication-naïve adults with ADHD and 31 healthy controls and tested whether this pattern was associated with symptoms severity scores. Results: ADHD sample showed increased local connectivity in the dACC and the SFG and decreased local connectivity in the PCC. Conclusion: Results parallel those obtained in children samples suggesting a deficient integration within the DMN and segregation between DMN, FPN, and VAN. These results are consistent with the three main frameworks that explain ADHD: the neurodevelopmental delay hypothesis, the DMN interference hypothesis, and multi-network models.

Virtual Ontogeny of Cortical Growth Preceding Mental Illness.

BACKGROUND: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. METHODS: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. RESULTS: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. CONCLUSIONS: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.

Tract-specific damage at spinal cord level in pure hereditary spastic paraplegia type 4: a diffusion tensor imaging study.

BACKGROUND: SPG4 is a subtype of hereditary spastic paraplegia (HSP), an upper motor neuron disorder characterized by axonal degeneration of the corticospinal tracts and the fasciculus gracilis. The few neuroimaging studies that have focused on the spinal cord in HSP are based mainly on the analysis of structural characteristics. METHODS: We assessed diffusion-related characteristics of the spinal cord using diffusion tensor imaging (DTI), as well as structural and shape-related properties in 12 SPG4 patients and 14 controls. We used linear mixed effects models up to T3 in order to analyze the global effects of 'group' and 'clinical data' on structural and diffusion data. For DTI, we carried out a region of interest (ROI) analysis in native space for the whole spinal cord, the anterior and lateral funiculi, and the dorsal columns. We also performed a voxelwise analysis of the spinal cord to study local diffusion-related changes. RESULTS: A reduced cross-sectional area was observed in the cervical region of SPG4 patients, with significant anteroposterior flattening. DTI analyses revealed significantly decreased fractional anisotropy (FA) and increased radial diffusivity at all the cervical and thoracic levels, particularly in the lateral funiculi and dorsal columns. The FA changes in SPG4 patients were significantly related to disease severity, measured as the Spastic Paraplegia Rating Scale score. CONCLUSIONS: Our results in SPG4 indicate tract-specific axonal damage at the level of the cervical and thoracic spinal cord. This finding is correlated with the degree of motor disability.

Feto-maternal microchimerism: Memories from pregnancy.

There is a bidirectional transplacental cell trafficking between mother and fetus during pregnancy in placental mammals. The presence and persistence of fetal cells in maternal tissues are known as fetal microchimerism (FMc). FMc has high multilineage potential with a great ability to differentiate and functionally integrate into maternal tissue. FMc has been found in various maternal tissues in animal models and humans. Its permanence in the maternal body up to decades after delivery suggests it might play an essential role in maternal pathophysiology. Studying the presence, localization, and characteristics of FMc in maternal tissues is key to understanding its impact on the woman's body. Here we comprehensively review the existence of FMc in different species and organs and tissues, aiming to better characterize their possible role in human health and disease. We also highlight several methodological considerations that would optimize the detection, quantification, and functional determination of FMc.

Corticospinal tract and motor cortex degeneration in pure hereditary spastic paraparesis type 4 (SPG4).

Objective: SPG4 is an autosomal dominant pure form of hereditary spastic paraplegia (HSP) caused by mutations in the SPAST gene. HSP is considered an upper motor neuron disorder characterized by progressive retrograde degeneration, or "dying-back" phenomenon, of the corticospinal tract's longest axons. Neuroimaging studies mainly focus on white matter changes and, although previous studies reported cortical thinning in complicated HSP forms, cortical changes remain unclear in SPG4 patients. This work aimed to compare changes in white matter microstructure and cortical thickness between 12 SPG4 patients and 22 healthy age-matched controls. We also explore whether white matter alterations are related to cortical thickness and their correlation with clinical symptoms. Methods: we used fixel-based analysis, an advanced diffusion-weighted imaging technique, and probabilistic tractography of the corticospinal tracts. We also analyzed cortical morphometry using whole-brain surface-based and atlas-based methods in sensorimotor areas. Results: SPG4 patients showed bilateral involvement in the corticospinal tracts; this was more intense in the distal portion than in the upper segments and was associated with the degree of clinical impairment. We found a significant correlation between disease severity and fiber density and cross-section of the corticospinal tracts. Furthermore, corticospinal tract changes were significantly correlated with bilateral cortical thinning in the precentral gyrus in SPG4 patients. Conclusions: Our data point to axonal damage of the corticospinal motor neurons in SPG4 patients might be related to cortical thinning in motor regions.

Characterizing the Brain Structural Adaptations Across the Motherhood Transition.

Women that become mothers face notable physiological adaptations during this life-period. Neuroimaging studies of the last decade have provided grounded evidence that women's brains structurally change across the transition into motherhood. The characterization of this brain remodeling is currently in its early years of research. The current article reviews this scientific field by focusing on our longitudinal (pre-to-post pregnancy) Magnetic Resonance Imaging (MRI) studies in first-time parents and other longitudinal and cross-sectional studies of parents. We present the questions that are currently being answered by the parental brain literature and point out those that have not yet been explored. We also highlight potential confounding variables that need to be considered when analyzing and interpreting brain changes observed during motherhood.

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.

Thalamic atrophy in patients with pure hereditary spastic paraplegia type 4.

SPG4 is an autosomal dominant pure form of hereditary spastic paraplegia (HSP) caused by mutations in the SPAST gene. HSP is considered an upper motor neuron disorder characterized by progressive spasticity and weakness of the lower limbs caused by degeneration of the corticospinal tract. In other neurodegenerative motor disorders, the thalamus and basal ganglia are affected, with a considerable impact on disease progression. However, only a few works have studied these brain structures in HSP, mainly in complex forms of this disease. Our research aims to detect potential alterations in the volume and shape of the thalamus and various basal ganglia structures by comparing 12 patients with pure HSP and 18 healthy controls. We used two neuroimaging procedures: automated segmentation of the subcortical structures (thalamus, hippocampus, caudate nucleus, globus pallidus, and putamen) in native space and shape analysis of the structures. We found a significant reduction in thalamic volume bilaterally, as well as an inward deformation, mainly in the sensory-motor thalamic regions in patients with pure HSP and a mutation in SPG4. We also observed a significant negative correlation between the shape of the thalamus and clinical scores (the Spastic Paraplegia Rating Scale score and disease duration). Moreover, we found a 'Group × Age' interaction that was closely related to the severity of the disease. No differences in volume or in shape were found in the remaining subcortical structures studied. Our results suggest that changes in structure of the thalamus could be an imaging biomarker of disease progression in pHSP.

The Paternal Transition Entails Neuroanatomic Adaptations that are Associated with the Father's Brain Response to his Infant Cues.

The transition into fatherhood is a life-changing event that requires substantial psychological adaptations. In families that include a father figure, sensitive paternal behavior has been shown to positively impact the infant's development. Yet, studies exploring the neuroanatomic adaptations of men in their transition into fatherhood are scarce. The present study used surface-based methods to reanalyze a previously published prospective magnetic resonance imaging dataset comprised of 20 first-time fathers (preconception-to-postpartum) and 17 childless men. We tested if the transition into fatherhood entailed changes in cortical volume, thickness, and area and whether these changes were related to 2 indicators of paternal experience. Specifically, we tested if such changes were associated with (1) the baby's age and/or (2) the fathers' brain activity in response to pictures of their babies compared with an unknown baby. Results indicated that first-time fathers exhibited a significant reduction in cortical volume and thickness of the precuneus. Moreover, higher volume reduction and cortical thinning were associated with stronger brain responses to pictures of their own baby in parental brain regions. This is the first study showing preconception-to-postpartum neuroanatomical adaptations in first-time fathers associated with the father's brain response to cues of his infant.

Presence of Distractor Improves Time Estimation Performance in an Adult ADHD Sample.

Objective: It is widely accepted that patients with ADHD exhibit greater susceptibility to distractors, especially during tasks with higher working memory load demands. However, no study to date has specifically measured the impact of distractors on timing functions, although these have consistently shown alterations in ADHD. In this investigation, we aimed to elucidate the neural mechanisms mediating distractor effects on timing functions. Method: We employed a time estimation functional magnetic resonance imaging (fMRI) paradigm including a distracting element in half of the trials in a sample of 21 patients with ADHD and 24 healthy controls. Results: As expected, the effect of the distractor was greater in ADHD patients, where it was associated with increased orbitofrontal activity compared with controls. Behaviorally, time estimation performance benefited from the presence of distractors in both groups. In turn, such improvement correlated with medial frontal and insular activity in the brain. Conclusion: These results suggest that distractors could be stimulating recruitment of frontal resources in ADHD, thus contributing to increase focus on the task.

Sensory-to-Cognitive Systems Integration Is Associated With Clinical Severity in Autism Spectrum Disorder.

OBJECTIVE: Impaired multisensory integration in autism spectrum disorder (ASD) may arise from functional dysconnectivity among brain systems. Our study examines the functional connectivity integration between primary modal sensory regions and heteromodal processing cortex in ASD, and whether abnormalities in network integration relate to clinical severity. METHOD: We studied a sample of 55 high-functioning ASD and 64 healthy control (HC) male children and adolescents (total n = 119, age range 7-18 years). Stepwise functional connectivity analysis (SFC) was applied to resting state functional magnetic resonance images (rsfMRI) to characterize the connectivity paths that link primary sensory cortices to higher-order brain cognitive functional circuits and to relate alterations in functional connectivity integration with three clinical scales: Social Communication Questionnaire, Social Responsiveness Scale, and Vineland Adaptive Behavior Scales. RESULTS: HC displayed typical functional connectivity transitions from primary sensory systems to association areas, but the ASD group showed altered patterns of multimodal sensory integration to heteromodal systems. Specifically, compared to the HC group, the ASD group showed the following: (1) hyperconnectivity in the visual cortex at initial link step distances; (2) hyperconnectivity between sensory unimodal regions and regions of the default mode network; and (3) hypoconnectivity between sensory unimodal regions and areas of the fronto-parietal and attentional networks. These patterns of hyper- and hypoconnectivity were associated with increased clinical severity in ASD. CONCLUSION: Networkwise reorganization in high-functioning ASD individuals affects strategic regions of unimodal-to-heteromodal cortical integration predicting clinical severity. In addition, SFC analysis appears to be a promising approach for studying the neural pathophysiology of multisensory integration deficits in ASD.

Becoming a mother entails anatomical changes in the ventral striatum of the human brain that facilitate its responsiveness to offspring cues.

In mothers, offspring cues are associated with a powerful reinforcing value that motivates maternal care. Animal studies show that this is mediated by dopamine release into the nucleus accumbens, a core component of the brain's reward system located in the ventral striatum (VStr). The VStr is also known to respond to infant signals in human mothers. However, it is unknown whether pregnancy modifies the anatomy or functionality of this structure, and whether such modifications underlie its strong reactivity to offspring cues. Therefore, we analyzed structural and functional neuroimaging data from a unique pre-conception prospective cohort study involving first-time mothers investigated before and after their pregnancy as well as nulliparous control women scanned at similar time intervals. First, we delineated the anatomy of the VStr in each subject's neuroanatomical space and examined whether there are volumetric changes in this structure across sessions. Then, we tested if these changes could predict the mothers' brain responses to visual stimuli of their infants. We found decreases in the right VStr and a trend for left VStr reductions in the women who were pregnant between sessions compared to the women who were not. Furthermore, VStr volume reductions across pregnancy were associated with infant-related VStr responses in the postpartum period, with stronger volume decreases predicting stronger functional activation to offspring cues. These findings provide the first indications that the transition to motherhood renders anatomical adaptations in the VStr that promote the strong responsiveness of a mother's reward circuit to cues of her infant.

Neuroimaging 'will to fight' for sacred values: an empirical case study with supporters of an Al Qaeda associate.

Violent intergroup conflicts are often motivated by commitments to abstract ideals such as god or nation, so-called 'sacred' values that are insensitive to material trade-offs. There is scant knowledge of how the brain processes costly sacrifices for such cherished causes. We studied willingness to fight and die for sacred values using fMRI in Barcelona, Spain, among supporters of a radical Islamist group. We measured brain activity in radicalized individuals as they indicated their willingness to fight and die for sacred and non-sacred values, and as they reacted to peers' ratings for the same values. We observed diminished activity in dorsolateral prefrontal cortex (dlPFC), inferior frontal gyrus, and parietal cortex while conveying willingness to fight and die for sacred relative to non-sacred values-regions that have previously been implicated in calculating costs and consequences. An overlapping region of the dlPFC was active when viewing conflicting ratings of sacred values from peers, to the extent participants were sensitive to peer influence, suggesting that it is possible to induce flexibility in the way people defend sacred values. Our results cohere with a view that 'devoted actors' motivated by an extreme commitment towards sacred values rely on distinctive neurocognitve processes that can be identified.

Stepwise functional connectivity reveals altered sensory-multimodal integration in medication-naïve adults with attention deficit hyperactivity disorder.

Neuroimaging studies indicate that children with attention-deficit/hyperactivity disorder (ADHD) present alterations in several functional networks of the sensation-to-cognition spectrum. These alterations include functional overconnectivity within sensory regions and underconnectivity between sensory regions and neural hubs supporting higher order cognitive functions. Today, it is unknown whether this same pattern of alterations persists in adult patients with ADHD who had never been medicated for their condition. The aim of the present study was to assess whether medication-naïve adults with ADHD presented alterations in functional networks of the sensation-to-cognition spectrum. Thirty-one medication-naïve adults with ADHD and twenty-two healthy adults underwent resting-state functional magnetic resonance imaging (rs-fMRI). Stepwise functional connectivity (SFC) was used to characterize the pattern of functional connectivity between sensory seed regions and the rest of the brain at direct, short, intermediate, and long functional connectivity distances, thus covering the continuum from the sensory input to the neural hubs supporting higher order cognitive functions. As compared to controls, adults with ADHD presented increased SFC degree within primary sensory regions and decreased SFC degree between sensory seeds and higher order integration nodes. In addition, they exhibited decreased connectivity degree between sensory seeds and regions of the default-mode network. Consistently, the higher the score in clinical severity scales the lower connectivity degree between seed regions and the default mode network.