Prenatal depressive symptoms are associated with altered structural brain networks in infants and moderated by infant sleep.

BACKGROUND: The prevalence of prenatal depressive symptoms has more than doubled during the COVID-19 pandemic, raising substantial concerns about child outcomes including sleep problems and altered brain development. The objective of this work was to determine relationships between prenatal depressive symptoms, infant brain network structure, and infant sleep. METHODS: Pregnant individuals were recruited as part of the Pregnancy during the Pandemic (PdP) study. Maternal depressive symptoms were measured in pregnancy and postpartum. When infants of those participants were 3 months of age (n=66; 26 females), infants underwent diffusion magnetic resonance imaging and infant sleep was evaluated. Using tractography, we calculated structural connectivity matrices for the default mode (DMN) and limbic networks. We examined associations between graph theory metrics of infant brain networks and prenatal maternal depressive symptoms, with infant sleep as a moderator. RESULTS: Prenatal depressive symptoms were negatively related to average DMN clustering coefficient and local efficiency in infant brains. Infant sleep duration was related to DMN global efficiency and moderated the relationship between prenatal depressive symptoms and density of limbic connections such that infants who slept less had a more negative relationship between prenatal depressive symptoms and local brain connectivity. CONCLUSIONS: Prenatal depressive symptoms appear to impact early topological development in brain networks important for emotion regulation. In the limbic network, sleep duration moderated this relationship, suggesting sleep may play a role in infant brain network development.

Multimodal brain features at 3 years of age and their relationship with pre-reading measures 1 year later.

Pre-reading language skills develop rapidly in early childhood and are related to brain structure and functional architecture in young children prior to formal education. However, the early neurobiological development that supports these skills is not well understood. Here we acquired anatomical, diffusion tensor imaging (DTI) and resting state functional MRI (rs-fMRI) from 35 children at 3.5 years of age. Children were assessed for pre-reading abilities using the NEPSY-II subtests 1 year later (4.5 years). We applied a data-driven linked independent component analysis (ICA) to explore the shared co-variation of gray and white matter measures. Two sources of structural variation at 3.5 years of age demonstrated relationships with Speeded Naming scores at 4.5 years of age. The first imaging component involved volumetric variability in reading-related cortical regions alongside microstructural features of the superior longitudinal fasciculus (SLF). The second component was dominated by cortical volumetric variations within the cerebellum and visual association area. In a subset of children with rs-fMRI data, we evaluated the inter-network functional connectivity of the left-lateralized fronto-parietal language network (FPL) and its relationship with pre-reading measures. Higher functional connectivity between the FPL and the default mode and visual networks at 3.5 years significantly predicted better Phonological Processing scores at 4.5 years. Together, these results suggest that the integration of functional networks, as well as the co-development of white and gray matter brain structures in early childhood, support the emergence of pre-reading measures in preschool children.

Prenatal Maternal Distress During the COVID-19 Pandemic and Associations With Infant Brain Connectivity.

BACKGROUND: The COVID-19 pandemic has caused substantially elevated distress in pregnant individuals, which has the potential to affect the developing infant brain. Our main objective was to understand how prenatal distress was related to infant brain structure and function and whether social support moderated the associations. METHODS: The Pregnancy during the COVID-19 Pandemic (PdP) cohort study collected Patient-Reported Outcomes Measurement Information System Anxiety scale, Edinburgh Postnatal Depression Scale, and Social Support Effectiveness Questionnaire data from a population-based sample of pregnant individuals living in Canada (N = 8602). For a subsample of participants, their infants (n = 75) underwent magnetic resonance imaging at 3 months of age to examine whether prenatal maternal distress was associated with infant brain architecture, including the role of social support as a potential protective factor. RESULTS: Overall, 33.4% of participants demonstrated clinically elevated depression symptoms and 47.1% of participants demonstrated clinically elevated anxiety symptoms. We identified lower social support as a significant predictor of clinically elevated prenatal maternal distress (t8598 = -22.3, p < .001). Fifty-eight diffusion image datasets (20 female/38 male, 92 ± 14 days old) and 41 functional datasets (13 female/28 male, 92 ± 14 days old) were included in our analysis after removal of poor-quality images and infants without postpartum maternal distress scores. We found significant relationships between prenatal maternal distress and infant amygdala-prefrontal microstructural and functional connectivity measures, and we demonstrate for the first time that social support moderates these relationships. CONCLUSIONS: Our findings suggest a potentially long-lasting impact of the COVID-19 pandemic on children and show that social support acts as a possible mediator not just for pregnant individuals but also developing infants. These findings provide timely evidence to inform clinical practice and policy surrounding the care of pregnant individuals and highlight the importance of social support.

Longitudinal changes of brain microstructure and function in nonconcussed female rugby players.

OBJECTIVE: To longitudinally assess brain microstructure and function in female varsity athletes participating in contact and noncontact sports. METHODS: Concussion-free female rugby players (n = 73) were compared to age-matched (ages 18-23) female swimmers and rowers (n = 31) during the in- and off-season. Diffusion and resting-state fMRI (rs-fMRI) measures were the primary outcomes. The Sports Concussion Assessment Tool and head impact accelerometers were used to monitor symptoms and impacts, respectively. RESULTS: We found cross-sectional (contact vs noncontact) and longitudinal (in- vs off-season) changes in white matter diffusion measures and rs-fMRI network connectivity in concussion-free contact athletes relative to noncontact athletes. In particular, mean, axial, and radial diffusivities were increased with decreased fractional anisotropy in multiple white matter tracts of contact athletes accompanied with default mode and visual network hyperconnectivity (p < 0.001). Longitudinal diffusion changes in the brainstem between the in- and off-season were observed for concussion-free contact athletes only, with progressive changes observed in a subset of athletes over multiple seasons. Axial diffusivity was significantly lower in the genu and splenium of the corpus callosum in those contact athletes with a history of concussion. CONCLUSIONS: Together, these findings demonstrate longitudinal changes in the microstructure and function of the brain in otherwise healthy, asymptomatic athletes participating in contact sport. Further research to understand the long-term brain health and biological implications of these changes is required, in particular to what extent these changes reflect compensatory, reparative, or degenerative processes.

Linked MRI signatures of the brain's acute and persistent response to concussion in female varsity rugby players.

Acute brain changes are expected after concussion, yet there is growing evidence of persistent abnormalities well beyond clinical recovery and clearance to return to play. Multiparametric MRI is a powerful approach to non-invasively study structure-function relationships in the brain, however it remains challenging to interpret the complex and heterogeneous cascade of brain changes that manifest after concussion. Emerging conjunctive, data-driven analysis approaches like linked independent component analysis can integrate structural and functional imaging data to produce linked components that describe the shared inter-subject variance across images. These linked components not only offer the potential of a more comprehensive understanding of the underlying neurobiology of concussion, but can also provide reliable information at the level of an individual athlete. In this study, we analyzed resting-state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI) within a cohort of female varsity rugby players (n = 52) through the in- and off-season, including concussed athletes (n = 21) who were studied longitudinally at three days, three months and six months after a diagnosed concussion. Linked components representing co-varying white matter microstructure and functional network connectivity characterized (a) the brain's acute response to concussion and (b) persistent alterations beyond clinical recovery. Furthermore, we demonstrate that these long-term brain changes related to specific aspects of a concussion history and allowed us to monitor individual athletes before and longitudinally after a diagnosed concussion.

Reduced brain glutamine in female varsity rugby athletes after concussion and in non-concussed athletes after a season of play.

The purpose of this study was to use non-invasive proton magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) to monitor changes in prefrontal white matter metabolite levels and tissue microstructure in female rugby players with and without concussion (ages 18-23, n = 64). Evaluations including clinical tests and 3 T MRI were performed at the beginning of a season (in-season) and followed up at the end of the season (off-season). Concussed athletes were additionally evaluated 24-72 hr (n = 14), three months (n = 11), and six months (n = 8) post-concussion. Reduced glutamine at 24-72 hr and three months post-concussion, and reduced glutamine/creatine at three months post-concussion were observed. In non-concussed athletes (n = 46) both glutamine and glutamine/creatine were lower in the off-season compared to in-season. Within the MRS voxel, an increase in fractional anisotropy (FA) and decrease in radial diffusivity (RD) were also observed in the non-concussed athletes, and correlated with changes in glutamine and glutamine/creatine. Decreases in glutamine and glutamine/creatine suggest reduced oxidative metabolism. Changes in FA and RD may indicate neuroinflammation or re-myelination. The observed changes did not correlate with clinical test scores suggesting these imaging metrics may be more sensitive to brain injury and could aid in assessing recovery of brain injury from concussion.

Multiparametric MRI changes persist beyond recovery in concussed adolescent hockey players.

OBJECTIVE: To determine whether multiparametric MRI data can provide insight into the acute and long-lasting neuronal sequelae after a concussion in adolescent athletes. METHODS: Players were recruited from Bantam hockey leagues in which body checking is first introduced (male, age 11-14 years). Clinical measures, diffusion metrics, resting-state network and region-to-region functional connectivity patterns, and magnetic resonance spectroscopy absolute metabolite concentrations were analyzed from an independent, age-matched control group of hockey players (n = 26) and longitudinally in concussed athletes within 24 to 72 hours (n = 17) and 3 months (n = 14) after a diagnosed concussion. RESULTS: There were diffusion abnormalities within multiple white matter tracts, functional hyperconnectivity, and decreases in choline 3 months after concussion. Tract-specific spatial statistics revealed a large region along the superior longitudinal fasciculus with the largest decreases in diffusivity measures, which significantly correlated with clinical deficits. This region also spatially intersected with probabilistic tracts connecting cortical regions where we found acute functional connectivity changes. Hyperconnectivity patterns at 3 months after concussion were present only in players with relatively less severe clinical outcomes, higher choline concentrations, and diffusivity indicative of relatively less axonal disruption. CONCLUSIONS: Changes persisted well after players' clinical scores had returned to normal and they had been cleared to return to play. Ongoing white matter maturation may make adolescent athletes particularly vulnerable to brain injury, and they may require extended recovery periods. The consequences of early brain injury for ongoing brain development and risk of more serious conditions such as second impact syndrome or neural degenerative processes need to be elucidated.

Spontaneous low frequency BOLD signal variations from resting-state fMRI are decreased in Alzheimer disease.

Previous studies have demonstrated altered brain activity in Alzheimer's disease using task based functional MRI (fMRI), network based resting-state fMRI, and glucose metabolism from 18F fluorodeoxyglucose-PET (FDG-PET). Our goal was to define a novel indicator of neuronal activity based on a first-order textural feature of the resting state functional MRI (RS-fMRI) signal. Furthermore, we examined the association between this neuronal activity metric and glucose metabolism from 18F FDG-PET. We studied 15 normal elderly controls (NEC) and 15 probable Alzheimer disease (AD) subjects from the AD Neuroimaging Initiative. An independent component analysis was applied to the RS-fMRI, followed by template matching to identify neuronal components (NC). A regional brain activity measurement was constructed based on the variation of the RS-fMRI signal of these NC. The standardized glucose uptake values of several brain regions relative to the cerebellum (SUVR) were measured from partial volume corrected FDG-PET images. Comparing the AD and NEC groups, the mean brain activity metric was significantly lower in the accumbens, while the glucose SUVR was significantly lower in the amygdala and hippocampus. The RS-fMRI brain activity metric was positively correlated with cognitive measures and amyloid ß1-42 cerebral spinal fluid levels; however, these did not remain significant following Bonferroni correction. There was a significant linear correlation between the brain activity metric and the glucose SUVR measurements. This proof of concept study demonstrates that this novel and easy to implement RS-fMRI brain activity metric can differentiate a group of healthy elderly controls from a group of people with AD.

Neuroplastic Sensorimotor Resting State Network Reorganization in Children With Hemiplegic Cerebral Palsy Treated With Constraint-Induced Movement Therapy.

Using resting state functional magnetic resonance imaging (MRI), we aim to understand the neurologic basis of improved function in children with hemiplegic cerebral palsy treated with constraint-induced movement therapy. Eleven children including 4 untreated comparison subjects diagnosed with hemiplegic cerebral palsy were recruited from 3 clinical centers. MRI and clinical data were gathered at baseline and 1 month for both groups, and 6 months later for the case group only. After constraint therapy, the sensorimotor resting state network became more bilateral, with balanced contributions from each hemisphere, which was sustained 6 months later. Sensorimotor resting state network reorganization after therapy was correlated with a change in the Quality of Upper Extremity Skills Test score at 1 month (r = 0.79, P = .06), and Canadian Occupational Performance Measure scores at 6 months (r = 0.82, P = .05). This clinically correlated resting state network reorganization provides further evidence of the neuroplastic mechanisms underlying constraint-induced movement therapy.

Resting State and Diffusion Neuroimaging Predictors of Clinical Improvements Following Constraint-Induced Movement Therapy in Children With Hemiplegic Cerebral Palsy.

The aim was to identify neuroimaging predictors of clinical improvements following constraint-induced movement therapy. Resting state functional magnetic resonance and diffusion tensor imaging data was acquired in 7 children with hemiplegic cerebral palsy. Clinical and magnetic resonance imaging (MRI) data were acquired at baseline and 1 month later following a 3-week constraint therapy regimen. A more negative baseline laterality index characterizing an atypical unilateral sensorimotor resting state network significantly correlated with an improvement in the Canadian Occupational Performance Measure score (r = -0.81, P = .03). A more unilateral network with decreased activity in the affected hemisphere was associated with greater improvements in clinical scores. Higher mean diffusivity in the posterior limb of the internal capsule of the affect tract correlated significantly with improvements in the Jebsen-Taylor score (r = -0.83, P = .02). Children with more compromised networks and tracts improved the most following constraint therapy.

Isoflurane induces dose-dependent alterations in the cortical connectivity profiles and dynamic properties of the brain's functional architecture.

Despite their widespread use, the effect of anesthetic agents on the brain's functional architecture remains poorly understood. This is particularly true of alterations that occur beyond the point of induced unconsciousness. Here, we examined the distributed intrinsic connectivity of macaques across six isoflurane levels using resting-state functional MRI (fMRI) following the loss of consciousness. The results from multiple analysis strategies showed stable functional connectivity (FC) patterns between 1.00% and 1.50% suggesting this as a suitable range for anesthetized nonhuman primate resting-state investigations. Dose-dependent effects were evident at moderate to high dosages showing substantial alteration of the functional topology and a decrease or complete loss of interhemispheric cortical FC strength including that of contralateral homologues. The assessment of dynamic FC patterns revealed that the functional repertoire of brain states is related to anesthesia depth and most strikingly, that the number of state transitions linearly decreases with increased isoflurane dosage. Taken together, the results indicate dose-specific spatial and temporal alterations of FC that occur beyond the typically defined endpoint of consciousness. Future work will be necessary to determine how these findings generalize across anesthetic types and extend to the transition between consciousness and unconsciousness.