Background
Extensive animal research has demonstrated the vulnerability of the brain to early life stress (ELS) with consequences for emotional development and mental health. However, the influence ...of moderate and common forms of stress on early human brain development is less well‐understood and precisely characterized. To date, most work has focused on severe forms of stress, and/or on brain functioning years after stress exposure.
Methods
In this report we focused on conflict between parents (interparental conflict), a common and relatively moderate form of ELS that is highly relevant for children's mental health outcomes. We used resting state functional connectivity MRI to examine the coordinated functioning of the infant brain (N = 23; 6–12‐months‐of‐age) in the context of interparental conflict. We focused on the default mode network (DMN) due to its well‐characterized developmental trajectory and implications for mental health. We further examined DMN strength as a mediator between conflict and infants’ negative emotionality.
Results
Higher interparental conflict since birth was associated with infants showing stronger connectivity between two core DMN regions, the posterior cingulate cortex (PCC) and the anterior medial prefrontal cortex (aMPFC). PCC to amygdala connectivity was also increased. Stronger PCC‐aMPFC connectivity mediated between higher conflict and higher negative infant emotionality.
Conclusions
The developing DMN may be an important marker for effects of ELS with relevance for emotional development and subsequent mental health. Increasing understanding of the associations between common forms of family stress and emerging functional brain networks has potential to inform intervention efforts to improve mental health outcomes.
Stream dewatering is expected to become more prevalent due to climate change, and we explored the potential consequences for brook trout (Salvelinus fontinalis) within a temperate forest ecosystem in ...eastern North America.
We estimated fish density within stream pools (n = 386) from electrofishing surveys over 10 years (2012–2021) to compare a stream that exhibits episodic dewatering (Paine Run) against a stream of similar size that remains flow‐connected (Staunton River) within Shenandoah National Park, Virginia (U.S.A.). Annual surveys encompassed fluvial distances ranging from 2.6 to 4.4 km in each stream.
Mean annual fish density (fish/pool m2) was not different between streams for juvenile or adult age classes, but spatial variation in density was greater in Paine Run for both age classes of fish. Paine Run also included a greater proportion of unoccupied pools than Staunton River and exhibited stronger spatial autocorrelation in fish density among nearby pools, suggesting dispersal limitation due to surface flow fragmentation.
Fish density in pools increased during years with low summer precipitation, and this effect was observed in both streams but was stronger in Paine Run than Staunton River, further indicating the importance of fish movement into pools in response to low‐flow thresholds.
Our results indicate the importance of pools as ecological refuges during low‐flow conditions and that episodic dewatering may affect extirpation risks for brook trout by sequestering more fish into fewer areas. Our findings also highlight the importance of hydrological variation within stream networks because downstream river gages could not predict the observed spatial heterogeneity in fish density or pool occupancy.
•fMRI research with infants and toddlers has increased rapidly over the past decade.•Infant fMRI has provided unique insight into early functional brain development.•Complex methodological challenges ...associated with infant fMRI warrant careful consideration and ongoing research.•Infant fMRI has potential to contribute to multiple fields of study.•The study of early life stress is a prime example of a field that is ripe to benefit from this technique.
Functional magnetic resonance imaging (fMRI) research with infants and toddlers has increased rapidly over the past decade, and provided a unique window into early brain development. In the current report, we review the state of the literature, which has established the feasibility and utility of task-based fMRI and resting state functional connectivity MRI (rs-fcMRI) during early periods of brain maturation. These methodologies have been successfully applied beginning in the neonatal period to increase understanding of how the brain both responds to environmental stimuli, and becomes organized into large-scale functional systems that support complex behaviors. We discuss the methodological challenges posed by this promising area of research. We also highlight that despite these challenges, early work indicates a strong potential for these methods to influence multiple research domains. As an example, we focus on the study of early life stress and its influence on brain development and mental health outcomes. We illustrate the promise of these methodologies for building on, and making important contributions to, the existing literature in this field.
This study focuses on characterizing the contributions of key terrestrial pathways that deliver dissolved organic carbon (DOC) to streams during hydrological events and on elucidating factors ...governing variation in water and DOC fluxes from these pathways. We made high‐frequency measurements of discharge, specific conductance (SC), and fluorescent dissolved organic matter (FDOM) during 221 events recorded over 2 years within four Vermont (USA) watersheds that range in area from 0.4 to 139 km2. Using the SC measurements, together with statistical information on discharge, we separated the event hydrographs into contributions from three terrestrial pathways, which we refer to as riparian quickflow, subsurface quickflow, and slow‐flow groundwater. The pathway discharges were used as input to a mixing model that closely approximated sub‐hourly streamwater DOC concentrations as measured with the FDOM sensors. Subsurface quickflow, comprised of pre‐event water, was the leading contributor to streamwater DOC fluxes, while riparian quickflow, comprised of event water, was the second‐leading contributor to streamwater DOC fluxes, despite comprising the smallest proportion of streamflow yield among the three end‐member pathways. Fixed‐effects regression analysis revealed that the relationship between DOC fluxes from the end‐member pathways and event magnitude was consistent across the four watersheds. This analysis also showed that DOC fluxes from the quickflow pathways increased significantly with temperature and varied inversely, but weakly, with catchment antecedent wetness. We believe that our approach, which leverages in‐stream sensors that enable high‐frequency measurements over extended periods, may be applicable for evaluating controls on DOC export from other watersheds within and beyond our study region.
Key Points
Calculations of a mixing model reproduce sub‐hourly observations of streamwater dissolved organic carbon (DOC) concentrations in four watersheds
Streamwater specific conductance can be used to quantify discharge from terrestrial flowpaths and constrain the DOC mixing model
DOC fluxes from principal flow paths vary discernibly with event magnitude, temperature, and antecedent wetness
Ineffective reduction of functional connectivity between the default mode network (DMN) and frontoparietal network (FPN) during cognitive control can interfere with performance in healthy ...individuals-a phenomenon present in psychiatric disorders, such as depression. Here, this mechanism is studied in healthy adolescents by examining gender differences in task-regressed functional connectivity using functional magnetic resonance imaging (MRI) and a novel task designed to place the DMN-supporting self-referential processing (SRP)-and FPN-supporting cognitive control-into conflict. Compared to boys, girls showed stronger functional connectivity between DMN and FPN during cognitive control in an SRP context (
= 40; boys = 20), a context that also elicited more errors of omission in girls. The gender difference in errors of omission was mediated by higher self-reported co-rumination-the extensive and repetitive discussion of problems and focus on negative feelings with a same-gender peer-by girls, compared to boys. These findings indicate that placing internal and external attentional demands in conflict lead to persistent functional connectivity between FPN and DMN in girls, but not boys; however, deficits in performance during this context were explained by co-rumination, such that youth with higher co-rumination displayed the largest performance deficits. Previous research shows that co-rumination predicts depressive symptoms during adolescence; thus, gender differences in the mechanisms involved with transitioning from internal to external processing may be relevant for understanding heightened vulnerability for depression in adolescent girls.
Characterizing typologies of childhood adversity may inform the development of risk profiles and corresponding interventions aimed at mitigating its lifelong consequences. A neurobiological grounding ...of these typologies requires systematic comparisons of neural structure and function among individuals with different exposure histories. Using seed-to-whole brain analyses, this study examined associations between childhood adversity and amygdala resting-state functional connectivity (rs-fc) in adolescents aged 11–19 years across three independent studies (N = 223; 127 adversity group) in both general and dimensional models of adversity (comparing abuse and neglect). In a general model, adversity was associated with altered amygdala rs-fc with clusters within the left anterior lateral prefrontal cortex. In a dimensional model, abuse was associated with altered amygdala rs-fc within the orbitofrontal cortex, dorsal precuneus, posterior cingulate cortex, and dorsal anterior cingulate cortex/anterior mid-cingulate cortex, as well as within the dorsal attention, visual, and somatomotor networks. Neglect was associated with altered amygdala rs-fc with the hippocampus, supplementary motor cortex, temporoparietal junction, and regions within the dorsal attention network. Both general and dimensional models revealed unique regions, potentially reflecting pathways by which distinct histories of adversity may influence adolescent behavior, cognition, and psychopathology.
Although groundwater exchange processes are known to modulate atmospheric influences on stream temperature and flow, the implications for ecological stability are poorly understood. Here, we ...evaluated temporal change in stream fish communities across a gradient of groundwater influence defined by karst terrain (carbonate parent materials) within the Potomac River basin of eastern North America. We surveyed 12 sites in 2022 that had been sampled 29–30 years previously with similar methods. We also collected stream temperature data from each site and used the regression slope of the air‐water temperature relationship to index stream thermal sensitivity and groundwater exchange processes. Sites in karst terrain exhibited strong groundwater controls on stream temperature, and fish communities were more stable over time in these locations than elsewhere. However, stream thermal sensitivity was a stronger predictor of species persistence than the spatial distribution of karst terrain in contributing areas, highlighting the ecological importance of local variation in groundwater discharge processes. The presence of calcium precipitates (marl) in stream substrates was associated with low thermal sensitivity and ecological stability over time, and we suggest such visible features may be a useful indicator of climate change refugia in stream ecosystems.
Telomere attrition is associated with disability accumulation and brain atrophy in multiple sclerosis (MS). Downstream of telomere attrition is cellular senescence. We sought to determine differences ...in the cellular senescence marker p16INK4a expression between MS and healthy control participants and the association of p16INK4a expression with MS disability and treatment exposure.
Patients meeting diagnostic criteria for MS and healthy controls were recruited for a cross-sectional pilot study. RNA was extracted from peripheral blood mononuclear cells (PBMCs) and p16INK4a expression levels were measured using qRT PCR. Spearman correlation coefficients and regression models were applied to compare expression levels to chronological age, assess case control differences, and determine associations with clinical outcome measures.
Fifty-two participants with MS (67 % female, ages 25–70) and 38 healthy controls (66 % female, ages 23–65) were included. p16INK4a levels were not linearly correlated with chronological age in MS (rhos = −0.01, p = 0.94) or control participants (rhos = 0.02, p = 0.92). Higher median p16INK4a levels were observed in the >50-year age group for MS (0.25, IQR 0.14–0.35) vs. controls (0.12, IQR 0.05–0.15) and in this age group B cell depletion therapy was associated with lower expression levels. p16INK4a expression was not associated with any of the measured MS disability outcomes.
Caution is needed with using p16INK4a expression level from PBMCs as an aging biomarker in MS participants, given lack of correlation with chronological age or large associations with clinical outcomes.
•Sixty-one percent of patients who were offered Evusheld chose to receive it.•Evusheld was largely well-tolerated among multiple sclerosis patients.•There were fewer COVID-19 infections in those who ...received Evusheld.•Antibody prophylaxis for viruses must consider evolving variants.
In December 2021, the U.S. Food and Drug Administration issued emergency use authorization for the combination monoclonal antibodies tixagevimab and cilgavimab (Evusheld – AstraZeneca) for COVID-19 pre-exposure prophylaxis. While COVID-19 vaccination is recommended for multiple sclerosis (MS) patients, there is concern for insufficient antibody response in patients receiving B-cell depleting therapies. The literature is sparse regarding the safety and efficacy of Evusheld use in MS patients.
We sought to investigate the administration, safety, and efficacy of Evusheld in MS patients.
Participants were consecutively recruited from the UCSD MS Center from July 2022 to October 2022. We conducted both a review of medical records and a prospective cohort study. Inclusion criteria included prior diagnosis of MS and eligibility for Evusheld injection due to use of B-cell depleting disease modifying therapy (DMT). All eligible patients were evaluated to determine uptake of Evusheld use. Participant surveys were distributed to Evusheld recipients that evaluated for potential Evusheld side effects and COVID-19 vaccination and infection history. The proportion of COVID-19 infections among participants with or without Evusheld use were compared using Fisher's exact test, and a negative binomial regression analysis was used to evaluate risk for COVID-19 infection after Evusheld administration.
A review of medical records showed that 79 MS patients were offered Evusheld by their clinicians during the recruitment period; 48 patients ultimately received the injection. Forty-two participants consented to the prospective cross-sectional study (mean age 46.4 years, 71.8 % female), of which 33 individuals received Evusheld. All participants received at least one COVID-19 vaccination dose, with 92.3 % receiving the initial series and at least one booster dose. One-third (30.8 %) of participants had a previous COVID-19 infection. DMTs included ocrelizumab, rituximab, and ofatumumab. Of the 33 participants who received Evusheld, 10 (30.3 %) reported experiencing at least one side effect. Injection site reactions included pain (most common), itchiness, and redness. General side effects included fatigue (most common), headache, muscle pain, and weakness. Of the 33 participants who received Evusheld, seven participants (21.2 %) tested positive for COVID-19 within 6 months of Evusheld injection. In an unadjusted binomial regression analysis, Evusheld administration was associated with a reduction in COVID-19 infection risk (OR 0.22, 95 % CI 0.05 – 1.02, p = 0.05). After adjusting for age and sex, Evusheld administration was still associated with a lower COVID-19 infection risk though it did not achieve nominal significance (OR 0.21, 95 % CI 0.04 - 1.09, p = 0.06). Of the 9 participants who were offered but did not receive Evusheld, five (55.6 %) tested positive for COVID-19 (p = 0.04 with Pearson's chi square test and p = 0.09 on Fisher's exact test).
Our medical records data demonstrated that only 61 % of MS patients offered Evusheld received the injection. Evusheld seems to be largely well-tolerated. No serious adverse effects were reported. The use of Evusheld was associated with fewer COVID-19 infections, but this did not reach nominal statistical significance in the modest sample size. The lessons learned from the initial Evusheld experience may be applied to future interventions directed at infection prevention in MS patients on immunomodulatory therapies.
Dissolved organic carbon (DOC) impacts water quality, the carbon cycle, and the ecology of aquatic systems. Understanding what controls DOC is therefore critical for improving large-scale models and ...best management practices for aquatic ecosystems. The two main processes of DOC transformation and removal, photochemical and microbial DOC degradation, work in tandem to modify and remineralize DOC within natural waters. Here, we examined both the photo- and microbial remineralization of DOC (photolability and biolability), and the indirect phototransformation of DOC into biolabile DOC (photoprimed biolability) for samples that capture the spatiotemporal and hydrological gradients of the Connecticut River watershed. The majority of DOC exported from this temperate watershed was photolabile and the concentration of photolabile DOC correlated with UV absorbance at 254 nm (
r
2
= 0.86). Phototransformation of DOC also increased biolability, and the total photolabile DOC (sum of photolabile and photoprimed biolabile DOC) showed a stronger correlation with UV absorbance at 254 nm (r
2
= 0.92). We estimate that as much as 49% (SD = 3.3%) and 10% (SD = 1.1%) of annual DOC export from the Connecticut River is directly photolabile and photoprimable, respectively. Thus, 2.82 Gg C year
−1
(SD = 0.67 Gg C year
−1
) or 1.13 Mg C km
−2
year
−1
(SD = 0.27 km
−2
year
−1
) of total photolabile DOC escapes photochemical degradation within the river network to be exported from the Connecticut River each year.
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