The maternal brain is more flexible and responsive at rest: effective connectivity of the parental caregiving network in postpartum mothers.

The field of neuroscience has largely overlooked the impact of motherhood on brain function outside the context of responses to infant stimuli. Here, we apply spectral dynamic causal modelling (spDCM) to resting-state fMRI data to investigate differences in brain function between a group of 40 first-time mothers at 1-year postpartum and 39 age- and education-matched women who have never been pregnant. Using spDCM, we investigate the directionality (top-down vs. bottom-up) and valence (inhibition vs excitation) of functional connections between six key left hemisphere brain regions implicated in motherhood: the dorsomedial prefrontal cortex, ventromedial prefrontal cortex, posterior cingulate cortex, parahippocampal gyrus, amygdala, and nucleus accumbens. We show a selective modulation of inhibitory pathways related to differences between (1) mothers and non-mothers, (2) the interactions between group and cognitive performance and (3) group and social cognition, and (4) differences related to maternal caregiving behaviour. Across analyses, we show consistent disinhibition between cognitive and affective regions suggesting more efficient, flexible, and responsive behaviour, subserving cognitive performance, social cognition, and maternal caregiving. Together our results support the interpretation of these key regions as constituting a parental caregiving network. The nucleus accumbens and the parahippocampal gyrus emerging as 'hub' regions of this network, highlighting the global importance of the affective limbic network for maternal caregiving, social cognition, and cognitive performance in the postpartum period.

The association between sex hormones and the change in brain-predicted age difference in older women.

OBJECTIVE: The role of circulating sex hormones on structural brain ageing is yet to be established. This study explored whether concentrations of circulating sex hormones in older women are associated with the baseline and longitudinal changes in structural brain ageing, defined by the brain-predicted age difference (brain-PAD). DESIGN: Prospective cohort study using data from NEURO and Sex Hormones in Older Women; substudies of the ASPirin in Reducing Events in the Elderly clinical trial. PATIENTS: Community-dwelling older women (aged 70+ years). MEASUREMENTS: Oestrone, testosterone, dehydroepiandrosterone (DHEA), and sex-hormone binding globulin (SHBG) were quantified from plasma samples collected at baseline. T1-weighted magnetic resonance imaging was performed at baseline, 1 and 3 years. Brain age was derived from whole brain volume using a validated algorithm. RESULTS: The sample comprised of 207 women not taking medications known to influence sex hormone concentrations. A statistically higher baseline brain-PAD (older brain age relative to chronological age) was seen for women in the highest DHEA tertile compared with the lowest in the unadjusted analysis (p = .04). This was not significant when adjusted for chronological age, and potential confounding health and behavioural factors. Oestrone, testosterone and SHBG were not associated with brain-PAD cross-sectionally, nor were any of the examined sex hormones or SHBG associated with brain-PAD longitudinally. CONCLUSION: No strong evidence of an association between circulating sex hormones and brain-PAD. Given there is prior evidence to suggests sex hormones may be important for brain ageing, further studies of circulating sex hormones and brain health in postmenopausal women are warranted.

Metabolic and functional connectivity provide unique and complementary insights into cognition-connectome relationships.

A major challenge in current cognitive neuroscience is how functional brain connectivity gives rise to human cognition. Functional magnetic resonance imaging (fMRI) describes brain connectivity based on cerebral oxygenation dynamics (hemodynamic connectivity), whereas [18F]-fluorodeoxyglucose functional positron emission tomography (FDG-fPET) describes brain connectivity based on cerebral glucose uptake (metabolic connectivity), each providing a unique characterization of the human brain. How these 2 modalities differ in their contribution to cognition and behavior is unclear. We used simultaneous resting-state FDG-fPET/fMRI to investigate how hemodynamic connectivity and metabolic connectivity relate to cognitive function by applying partial least squares analyses. Results revealed that although for both modalities the frontoparietal anatomical subdivisions related the strongest to cognition, using hemodynamic measures this network expressed executive functioning, episodic memory, and depression, whereas for metabolic measures this network exclusively expressed executive functioning. These findings demonstrate the unique advantages that simultaneous FDG-PET/fMRI has to provide a comprehensive understanding of the neural mechanisms that underpin cognition and highlights the importance of multimodality imaging in cognitive neuroscience research.

Evidence of Subjective, But Not Objective, Cognitive Deficit in New Mothers at 1-Year Postpartum.

Background: The experience and even existence of cognitive deficits in the postpartum period is uncertain, with only a few scientific studies, reporting inconsistent results. Methods: In this study, we investigate cognition in 86 women (43 first-time mothers 1 year postpartum and 43 non-mothers). Results: Mothers and non-mothers showed no significant differences on measures of objective cognition (verbal memory, working memory, and processing speed or theory of mind). Despite the absence of objective differences, mothers self-reported significantly worse subjective memory than non-mothers. To interpret the difference between objective and subjective measures of memory, we investigated relationships between subjective memory, objective memory, and wellbeing. Mothers, but not non-mothers, showed a positive correlation between subjective and objective measures of memory, indicating mothers are "in-tune" with their memory performance. Mothers also demonstrated a positive relationship between subjective memory and wellbeing (sleep, anxiety, and depression), where better wellbeing correlated with higher subjective memory. This relationship was not apparent in non-mothers. The results suggest that poorer sleep, higher anxiety, and higher depression are related to reports of poorer self-reported memory in mothers. Conclusion: Our results add to our growing understanding of maternal cognition at 1 year postpartum, with no evidence of cognitive differences between mothers and non-mothers.

Monash DaCRA fPET-fMRI: A dataset for comparison of radiotracer administration for high temporal resolution functional FDG-PET.

BACKGROUND: "Functional" [18F]-fluorodeoxyglucose positron emission tomography (FDG-fPET) is a new approach for measuring glucose uptake in the human brain. The goal of FDG-fPET is to maintain a constant plasma supply of radioactive FDG in order to track, with high temporal resolution, the dynamic uptake of glucose during neuronal activity that occurs in response to a task or at rest. FDG-fPET has most often been applied in simultaneous BOLD-fMRI/FDG-fPET (blood oxygenation level-dependent functional MRI fluorodeoxyglucose functional positron emission tomography) imaging. BOLD-fMRI/FDG-fPET provides the capability to image the 2 primary sources of energetic dynamics in the brain, the cerebrovascular haemodynamic response and cerebral glucose uptake. FINDINGS: In this Data Note, we describe an open access dataset, Monash DaCRA fPET-fMRI, which contrasts 3 radiotracer administration protocols for FDG-fPET: bolus, constant infusion, and hybrid bolus/infusion. Participants (n = 5 in each group) were randomly assigned to each radiotracer administration protocol and underwent simultaneous BOLD-fMRI/FDG-fPET scanning while viewing a flickering checkerboard. The bolus group received the full FDG dose in a standard bolus administration, the infusion group received the full FDG dose as a slow infusion over the duration of the scan, and the bolus-infusion group received 50% of the FDG dose as bolus and 50% as constant infusion. We validate the dataset by contrasting plasma radioactivity, grey matter mean uptake, and task-related activity in the visual cortex. CONCLUSIONS: The Monash DaCRA fPET-fMRI dataset provides significant reuse value for researchers interested in the comparison of signal dynamics in fPET, and its relationship with fMRI task-evoked activity.

Brain susceptibility imaging provides valuable in vivo insights into cerebellar diseases, but biological interpretations remain elusive.

This scientific commentary relates to: 'Quantitative susceptibility mapping reveals alterations of dentate nuclei in common types of degenerative cerebellar ataxias' by Deistung et al. (https://doi.org/10.1093/braincomms/fcab306).

Health-related heterogeneity in brain aging and associations with longitudinal change in cognitive function.

Introduction: Neuroimaging-based 'brain age' can identify individuals with 'advanced' or 'resilient' brain aging. Brain-predicted age difference (brain-PAD) is predictive of cognitive and physical health outcomes. However, it is unknown how individual health and lifestyle factors may modify the relationship between brain-PAD and future cognitive or functional performance. We aimed to identify health-related subgroups of older individuals with resilient or advanced brain-PAD, and determine if membership in these subgroups is differentially associated with changes in cognition and frailty over three to five years. Methods: Brain-PAD was predicted from T1-weighted images acquired from 326 community-dwelling older adults (73.8 ± 3.6 years, 42.3% female), recruited from the larger ASPREE (ASPirin in Reducing Events in the Elderly) trial. Participants were grouped as having resilient (n=159) or advanced (n=167) brain-PAD, and latent class analysis (LCA) was performed using a set of cognitive, lifestyle, and health measures. We examined associations of class membership with longitudinal change in cognitive function and frailty deficit accumulation index (FI) using linear mixed models adjusted for age, sex and education. Results: Subgroups of resilient and advanced brain aging were comparable in all characteristics before LCA. Two typically similar latent classes were identified for both subgroups of brain agers: class 1 were characterized by low prevalence of obesity and better physical health and class 2 by poor cardiometabolic, physical and cognitive health. Among resilient brain agers, class 1 was associated with a decrease in cognition, and class 2 with an increase over 5 years, though was a small effect that was equivalent to a 0.04 standard deviation difference per year. No significant class distinctions were evident with FI. For advanced brain agers, there was no evidence of an association between class membership and changes in cognition or FI. Conclusion: These results demonstrate that the relationship between brain age and cognitive trajectories may be influenced by other health-related factors. In particular, people with age-resilient brains had different trajectories of cognitive change depending on their cognitive and physical health status at baseline. Future predictive models of aging outcomes will likely be aided by considering the mediating or synergistic influence of multiple lifestyle and health indices alongside brain age.

Task-evoked simultaneous FDG-PET and fMRI data for measurement of neural metabolism in the human visual cortex.

Understanding how the living human brain functions requires sophisticated in vivo neuroimaging technologies to characterise the complexity of neuroanatomy, neural function, and brain metabolism. Fluorodeoxyglucose positron emission tomography (FDG-PET) studies of human brain function have historically been limited in their capacity to measure dynamic neural activity. Simultaneous [18 F]-FDG-PET and functional magnetic resonance imaging (fMRI) with FDG infusion protocols enable examination of dynamic changes in cerebral glucose metabolism simultaneously with dynamic changes in blood oxygenation. The Monash vis-fPET-fMRI dataset is a simultaneously acquired FDG-fPET/BOLD-fMRI dataset acquired from n = 10 healthy adults (18-49 yrs) whilst they viewed a flickering checkerboard task. The dataset contains both raw (unprocessed) images and source data organized according to the BIDS specification. The source data includes PET listmode, normalization, sinogram and physiology data. Here, the technical feasibility of using opensource frameworks to reconstruct the PET listmode data is demonstrated. The dataset has significant re-use value for the development of new processing pipelines, signal optimisation methods, and to formulate new hypotheses concerning the relationship between neuronal glucose uptake and cerebral haemodynamics.

Emerging Applications for Quantitative Susceptibility Mapping in the Detection of Traumatic Brain Injury Pathology.

Traumatic brain injury (TBI) is a common but heterogeneous injury underpinned by numerous complex and interrelated pathophysiological mechanisms. An essential trace element, iron is abundant within the brain and involved in many fundamental neurobiological processes, including oxygen transportation, oxidative phosphorylation, myelin production and maintenance, as well as neurotransmitter synthesis and metabolism. Excessive levels of iron are neurotoxic and thus iron homeostasis is tightly regulated in the brain, however, many details about the mechanisms by which this is achieved are yet to be elucidated. A key mediator of oxidative stress, mitochondrial dysfunction and neuroinflammatory response, iron dysregulation is an important contributor to secondary injury in TBI. Advances in neuroimaging that leverage magnetic susceptibility properties have enabled increasingly comprehensive investigations into the distribution and behaviour of iron in the brain amongst healthy individuals as well as disease states such as TBI. Quantitative Susceptibility Mapping (QSM) is an advanced neuroimaging technique that promises quantitative estimation of local magnetic susceptibility at the voxel level. In this review, we provide an overview of brain iron and its homeostasis, describe recent advances enabling applications of QSM within the context of TBI and summarise the current state of the literature. Although limited, the emergent research suggests that QSM is a promising neuroimaging technique that can be used to investigate a host of pathophysiological changes that are associated with TBI.

Metabolic and Hemodynamic Resting-State Connectivity of the Human Brain: A High-Temporal Resolution Simultaneous BOLD-fMRI and FDG-fPET Multimodality Study.

Simultaneous [18F]-fluorodeoxyglucose positron emission tomography functional magnetic resonance imaging (FDG-PET/fMRI) provides the capacity to image 2 sources of energetic dynamics in the brain-glucose metabolism and the hemodynamic response. fMRI connectivity has been enormously useful for characterizing interactions between distributed brain networks in humans. Metabolic connectivity based on static FDG-PET has been proposed as a biomarker for neurological disease, but FDG-sPET cannot be used to estimate subject-level measures of "connectivity," only across-subject "covariance." Here, we applied high-temporal resolution constant infusion functional positron emission tomography (fPET) to measure subject-level metabolic connectivity simultaneously with fMRI connectivity. fPET metabolic connectivity was characterized by frontoparietal connectivity within and between hemispheres. fPET metabolic connectivity showed moderate similarity with fMRI primarily in superior cortex and frontoparietal regions. Significantly, fPET metabolic connectivity showed little similarity with FDG-sPET metabolic covariance, indicating that metabolic brain connectivity is a nonergodic process whereby individual brain connectivity cannot be inferred from group-level metabolic covariance. Our results highlight the complementary strengths of fPET and fMRI in measuring the intrinsic connectivity of the brain and open up the opportunity for novel fundamental studies of human brain connectivity as well as multimodality biomarkers of neurological diseases.

"Phantom Kicks": Women's Subjective Experience of Fetal Kicks After the Postpartum Period.

Background: During pregnancy, a woman will attribute increased abdominal sensations to fetal movement. Surprisingly, many women report that they feel kick sensations long after the pregnancy; however, this experience has never been reported in the scientific literature. Materials and Methods: We used a qualitative approach to survey n = 197 women who had previously been pregnant. We calculated the number of women who had experienced phantom kicks after their first pregnancy, and explored subjective experiences of kick-like sensations in the post-partum period. Results: In this study, we show that almost 40% of women in our sample experienced phantom fetal kicks after their first pregnancy, up to 28 years (average 6.4 years) post-partum. Women described the phantom sensations as "convincing," "real kicks," or "flutters." Twenty-seven percent of women described the experience as nostalgic or comforting, and 25.7% reported felt confused or upset by the experience. Conclusions: Our results demonstrate that phantom kicks in the postpartum period are a widely experienced sensation, which may have implications for a woman's postpartum mental health. The mechanism behind the phantom kick phenomenon is unknown, but may be related to changes in the somatosensory homunculus or proprioception during pregnancy.

Neuroprotective Effects of Motherhood on Brain Function in Late Life: A Resting-State fMRI Study.

The maternal brain undergoes structural and functional plasticity during pregnancy and the postpartum period. Little is known about functional plasticity outside caregiving-specific contexts and whether changes persist across the lifespan. Structural neuroimaging studies suggest that parenthood may confer a protective effect against the aging process; however, it is unknown whether parenthood is associated with functional brain differences in late life. We examined the relationship between resting-state functional connectivity and number of children parented in 220 healthy older females (73.82 ± 3.53 years) and 252 healthy older males (73.95 ± 3.50 years). We compared the patterns of resting-state functional connectivity with 3 different models of age-related functional change to assess whether these effects may be functionally neuroprotective for the aging human parental brain. No relationship between functional connectivity and number of children was obtained for males. For females, we found widespread decreasing functional connectivity with increasing number of children parented, with increased segregation between networks, decreased connectivity between hemispheres, and decreased connectivity between anterior and posterior regions. The patterns of functional connectivity related to the number of children an older woman has parented were in the opposite direction to those usually associated with age-related cognitive decline, suggesting that motherhood may be beneficial for brain function in late life.

Estimation of simultaneous BOLD and dynamic FDG metabolic brain activations using a multimodality concatenated ICA (mcICA) method.

Simultaneous magnetic resonance and positron emission tomography provides an opportunity to measure brain haemodynamics and metabolism in a single scan session, and to identify brain activations from multimodal measurements in response to external stimulation. However, there are few analysis methods available for jointly analysing the simultaneously acquired blood-oxygen-level dependant functional MRI (fMRI) and 18-F-fluorodeoxyglucose functional PET (fPET) datasets. In this work, we propose a new multimodality concatenated ICA (mcICA) method to identify joint fMRI-fPET brain activations in response to a visual stimulation task. The mcICA method produces a fused map from the multimodal datasets with equal contributions of information from both modalities, measured by entropy. We validated the method in silico, and applied it to an in vivo visual stimulation experiment. The mcICA method estimated the activated brain regions in the visual cortex modulated by both BOLD and FDG signals. The mcICA provides a fully data-driven analysis approach to analyse cerebral haemodynamic response and glucose uptake signals arising from exogenously induced neuronal activity.

Simultaneous BOLD-fMRI and constant infusion FDG-PET data of the resting human brain.

Simultaneous [18 F]-fluorodeoxyglucose positron emission tomography and functional magnetic resonance imaging (FDG-PET/fMRI) provides the capability to image two sources of energetic dynamics in the brain - cerebral glucose uptake and the cerebrovascular haemodynamic response. Resting-state fMRI connectivity has been enormously useful for characterising interactions between distributed brain regions in humans. Metabolic connectivity has recently emerged as a complementary measure to investigate brain network dynamics. Functional PET (fPET) is a new approach for measuring FDG uptake with high temporal resolution and has recently shown promise for assessing the dynamics of neural metabolism. Simultaneous fMRI/fPET is a relatively new hybrid imaging modality, with only a few biomedical imaging research facilities able to acquire FDG PET and BOLD fMRI data simultaneously. We present data for n = 27 healthy young adults (18-20 yrs) who underwent a 95-min simultaneous fMRI/fPET scan while resting with their eyes open. This dataset provides significant re-use value to understand the neural dynamics of glucose metabolism and the haemodynamic response, the synchrony, and interaction between these measures, and the development of new single- and multi-modality image preparation and analysis procedures.

Individual differences in haemoglobin concentration influence bold fMRI functional connectivity and its correlation with cognition.

Resting-state connectivity measures the temporal coherence of the spontaneous neural activity of spatially distinct regions, and is commonly measured using BOLD-fMRI. The BOLD response follows neuronal activity, when changes in the relative concentration of oxygenated and deoxygenated haemoglobin cause fluctuations in the MRI T2* signal. Since the BOLD signal detects changes in relative concentrations of oxy/deoxy-haemoglobin, individual differences in haemoglobin levels may influence the BOLD signal-to-noise ratio in a manner independent of the degree of neural activity. In this study, we examined whether group differences in haemoglobin may confound measures of functional connectivity. We investigated whether relationships between measures of functional connectivity and cognitive performance could be influenced by individual variability in haemoglobin. Finally, we mapped the neuroanatomical distribution of the influence of haemoglobin on functional connectivity to determine where group differences in functional connectivity are manifest. In a cohort of 518 healthy elderly subjects (259 men), each sex group was median-split into two groups with high and low haemoglobin concentration. Significant differences were obtained in functional connectivity between the high and low haemoglobin groups for both men and women (Cohen's d 0.17 and 0.03 for men and women respectively). The haemoglobin connectome in males showed a widespread systematic increase in functional connectivity correlation values, whilst the female connectome showed predominantly parietal and subcortical increases and temporo-parietal decreases. Despite the haemoglobin groups having no differences in cognitive measures, significant differences in the linear relationships between cognitive performance and functional connectivity were obtained for all 5 cognitive tests in males, and 4 out of 5 tests in females. Our findings confirm that individual variability in haemoglobin levels that give rise to group differences are an important confounding variable in BOLD-fMRI-based studies of functional connectivity. Controlling for haemoglobin variability as a potentially confounding variable is crucial to ensure the reproducibility of human brain connectome studies, especially in studies that compare groups of individuals, compare sexes, or examine connectivity-cognition relationships.

Relationship between parenthood and cortical thickness in late adulthood.

Pregnancy and the early postpartum period alter the structure of the brain; particularly in regions related to parental care. However, the enduring effects of this period on human brain structure and cognition in late life is unknown. Here we use magnetic resonance imaging to examine differences in cortical thickness related to parenthood in late life, for both sexes. In 235 healthy older women, we find a positive relationship between parity (number of children parented) and memory performance in mothers. Parity was also associated with differences in cortical thickness in women in the parahippocampus, precuneus, cuneus and pericalcarine sulcus. We also compared non-parents to parents of one child, in a sub-sample of older women (N = 45) and men (N = 35). For females, six regions differed in cortical thickness between parents and non-parents; these regions were consistent with those seen earlier in life in previous studies. For males, five regions differed in cortical thickness between parents and non-parents. We are first to reveal parenthood-related brain differences in late-life; our results are consistent with previously identified areas that are altered during pregnancy and the postpartum period. This study provides preliminary evidence to suggest that neural changes associated with early stages of parenthood persist into older age, and for women, may be related to marginally better cognitive outcomes.

Serial assessment of iron in the motor cortex in limb-onset amyotrophic lateral sclerosis using quantitative susceptibility mapping.

BACKGROUND: Dysregulation of iron in the cerebral motor areas has been hypothesized to occur in individuals with amyotrophic lateral sclerosis (ALS). There is still limited knowledge regarding iron dysregulation in the progression of ALS pathology. Our objectives were to use magnetic resonance based quantitative susceptibility mapping (QSM) to investigate the association between iron dysregulation in the motor cortex and clinical manifestations in patients with limb-onset ALS, and to examine changes in the iron concentration in the motor cortex in these patients over a 6-month period. METHODS: Iron concentration was investigated using magnetic resonance based QSM in the primary motor cortex and the pre-motor area in 13 limb-onset ALS patients (including five lumbar onset, six cervical onset and two flail arm patients), and 11 age- and sex-matched control subjects. Nine ALS patients underwent follow-up scans at 6 months. RESULTS: Significantly increased QSM values were observed in the left posterior primary motor area (P=0.02, Cohen's d =0.9) and right anterior primary motor area (P=0.02, Cohen's d =0.92) in the group of limb-onset ALS patients compared to that of control subjects. Increased QSM was observed in the primary motor and pre-motor area at baseline in patients with lumbar onset ALS patients, but not cervical limb-onset ALS patients, compared to control subjects. No significant change in QSM was observed at the 6-month follow-up scans in the ALS patients. CONCLUSIONS: The findings suggest that iron dysregulation can be detected in the motor cortex in limb-onset ALS, which does not appreciably change over a further 6 months. Individuals with lumbar onset ALS appear to be more susceptible to motor cortex iron dysregulation compared to the individuals with cervical onset ALS. Importantly, this study highlights the potential use of QSM as a quantitative radiological indicator in early disease diagnosis in limb-onset ALS and its subtypes. Our serial scans results suggest a longer period than 6 months is needed to detect significant quantitative changes in the motor cortex.

Effective Self-Management for Early Career Researchers in the Natural and Life Sciences.

Early career researchers (ECRs) are faced with a range of competing pressures in academia, making self-management key to building a successful career. The Organization for Human Brain Mapping undertook a group effort to gather helpful advice for ECRs in self-management.

Analysis of continuous infusion functional PET (fPET) in the human brain.

Functional positron emission tomography (fPET) is a neuroimaging method involving continuous infusion of 18-F-fluorodeoxyglucose (FDG) radiotracer during the course of a PET examination. Compared with the conventional bolus administration of FDG in a static PET scan, which provides an average glucose uptake into the brain over an extended period of up to 30 â€‹min, fPET offers a significantly higher temporal resolution to study the dynamics of glucose uptake. Several earlier studies have applied fPET to investigate brain FDG uptake and study its relationship with functional magnetic resonance imaging (fMRI). However, due to the unique characteristics of fPET signals, modelling of the fPET signal is a complex task and poses challenges for accurate interpretation of the results from fPET experiments. This study applied independent component analysis (ICA) to analyse resting state fPET data, and to compare the performance of ICA and the general linear model (GLM) for estimation of brain activation in response to tasks. The fPET signal characteristics were compared using GLM and ICA methods to model fPET data from a visual activation experiment. Our aim was to evaluate GLM and ICA methods for analysing task fPET datasets, and to apply ICA methods to the analysis of resting state fPET datasets. Using both simulation and in-vivo experimental datasets, we show that both ICA and GLM methods can successfully identify task related brain activation. We report fPET metabolic resting state brain networks revealed by application of the fPET ICA method to a cohort of 28 healthy subjects. Functional PET provides a unique method to map dynamic changes of glucose uptake in the resting human brain and in response to extrinsic stimulation.