Acute psychosocial stress modulates neural and behavioral substrates of cognitive control.

Acute psychosocial stress affects learning, memory, and attention, but the evidence for the influence of stress on the neural processes supporting cognitive control remains mixed. We investigated how acute psychosocial stress influences performance and neural processing during the Go/NoGo task-an established cognitive control task. The experimental group underwent the Trier Social Stress Test (TSST) acute stress induction, whereas the control group completed personality questionnaires. Then, participants completed a functional magnetic resonance imaging (fMRI) Go/NoGo task, with self-report, blood pressure and salivary cortisol measurements of induced stress taken intermittently throughout the experimental session. The TSST was successful in eliciting a stress response, as indicated by significant Stress > Control between-group differences in subjective stress ratings and systolic blood pressure. We did not identify significant differences in cortisol levels, however. The stress induction also impacted subsequent Go/NoGo task performance, with participants who underwent the TSST making fewer commission errors on trials requiring the most inhibitory control (NoGo Green) relative to the control group, suggesting increased vigilance. Univariate analysis of fMRI task-evoked brain activity revealed no differences between stress and control groups for any region. However, using multivariate pattern analysis, stress and control groups were reliably differentiated by activation patterns contrasting the most demanding NoGo trials (i.e., NoGo Green trials) versus baseline in the medial intraparietal area (mIPA, affiliated with the dorsal attention network) and subregions of the cerebellum (affiliated with the default mode network). These results align with prior reports linking the mIPA and the cerebellum to visuomotor coordination, a function central to cognitive control processes underlying goal-directed behavior. This suggests that stressor-induced hypervigilance may produce a facilitative effect on response inhibition which is represented neurally by the activation patterns of cognitive control regions.

Correction: The solution structures and relative stability constants of lanthanide-EDTA complexes predicted from computation.

Correction for 'The solution structures and relative stability constants of lanthanide-EDTA complexes predicted from computation' by Ravi D. O'Brien et al., Phys. Chem. Chem. Phys., 2022, 24, 10263-10271, https://doi.org/10.1039/D2CP01081J.

Ultrasound-Guided Occipital Nerve Blocks as Part of Multi-Modal Perioperative Analgesia in Pediatric Posterior Craniotomies: A Case Series.

Various regional anesthetics have been used for postoperative analgesia for pediatric craniotomy. In this case series, we report retrospectively collected data on postoperative pain and analgesic use in 44 patients who received ultrasound-guided occipital nerve blocks in addition to intravenous analgesic agents for posterior craniotomy procedures. In the immediate post-anesthesia care unit, pain was rated as zero or well controlled in 77% of patients, with only 43% requiring intravenous or demand patient-controlled analgesia opioids. There were no block-related complications. Occipital nerve blocks may constitute a safe and effective component of multimodal analgesia in this population.

Neural representation dynamics reveal computational principles of cognitive task learning.

During cognitive task learning, neural representations must be rapidly constructed for novel task performance, then optimized for robust practiced task performance. How the geometry of neural representations changes to enable this transition from novel to practiced performance remains unknown. We hypothesized that practice involves a shift from compositional representations (task-general activity patterns that can be flexibly reused across tasks) to conjunctive representations (task-specific activity patterns specialized for the current task). Functional MRI during learning of multiple complex tasks substantiated this dynamic shift from compositional to conjunctive representations, which was associated with reduced cross-task interference (via pattern separation) and behavioral improvement. Further, we found that conjunctions originated in subcortex (hippocampus and cerebellum) and slowly spread to cortex, extending multiple memory systems theories to encompass task representation learning. The formation of conjunctive representations hence serves as a computational signature of learning, reflecting cortical-subcortical dynamics that optimize task representations in the human brain.

Causally informed activity flow models provide mechanistic insight into network-generated cognitive activations.

Brain activity flow models estimate the movement of task-evoked activity over brain connections to help explain network-generated task functionality. Activity flow models have been shown to accurately generate task-evoked brain activations across a wide variety of brain regions and task conditions. However, these models have had limited explanatory power, given known issues with causal interpretations of the standard functional connectivity measures used to parameterize activity flow models. We show here that functional/effective connectivity (FC) measures grounded in causal principles facilitate mechanistic interpretation of activity flow models. We progress from simple to complex FC measures, with each adding algorithmic details reflecting causal principles. This reflects many neuroscientists' preference for reduced FC measure complexity (to minimize assumptions, minimize compute time, and fully comprehend and easily communicate methodological details), which potentially trades off with causal validity. We start with Pearson correlation (the current field standard) to remain maximally relevant to the field, estimating causal validity across a range of FC measures using simulations and empirical fMRI data. Finally, we apply causal-FC-based activity flow modeling to a dorsolateral prefrontal cortex region (DLPFC), demonstrating distributed causal network mechanisms contributing to its strong activation during a working memory task. Notably, this fully distributed model is able to account for DLPFC working memory effects traditionally thought to rely primarily on within-region (i.e., not distributed) recurrent processes. Together, these results reveal the promise of parameterizing activity flow models using causal FC methods to identify network mechanisms underlying cognitive computations in the human brain.

Effect of Oral Nutritional Supplementation on Adequacy of Nutrient Intake among Picky-Eating Children at Nutritional Risk in India: A Randomized Double Blind Clinical Trial.

Nutrient inadequacies among picky-eaters have adverse effects on growth and development. Oral nutritional supplements (ONS) along with dietary counseling (DC), rather than DC alone as reported in our earlier publication, promoted growth among picky-eating Indian children aged from >24 m to ≤48 m with weight-for-height percentiles lying between the 5th and 25th (based on WHO Growth Standards) over 90 days. This paper presents the contribution of ONS to nutrient adequacy, dietary diversity, and food consumption patterns in children (N = 321). Weight, height, and dietary intakes, using 24-h food recalls, were measured at baseline (Day 1) and at Days 7, 30, 60, and 90. Nutrient adequacy, dietary diversity score (DDS), and food intake adequacy were calculated in both the supplementation groups (ONS1 + DC and ONS2 + DC; n = 107 in each group) and the control group (DC-only; n = 107). Supplements increased nutrient adequacy in both of the ONS + DC groups relative to control (p < 0.05). The proportions of children with adequate nutrient intakes increased significantly at Day 90 in the supplemented groups as compared to in the control group (p < 0.05), especially for total fat, calcium, vitamin A, vitamin C, and thiamin. Although no significant differences were observed in DDS in any of the groups, the percentage of children consuming ≥4 food groups in a day had increased in all the groups. Consumption of fruit and vegetables and cereals had increased significantly from baseline to Day 90. ONS along with dietary counseling was found to have improved nutritional adequacy without interfering with the normal food consumption patterns of picky-eating children at nutritional risk.

Rapid and precise genome engineering in a naturally short-lived vertebrate.

The African turquoise killifish is a powerful vertebrate system to study complex phenotypes at scale, including aging and age-related disease. Here, we develop a rapid and precise CRISPR/Cas9-mediated knock-in approach in the killifish. We show its efficient application to precisely insert fluorescent reporters of different sizes at various genomic loci in order to drive cell-type- and tissue-specific expression. This knock-in method should allow the establishment of humanized disease models and the development of cell-type-specific molecular probes for studying complex vertebrate biology.

Life Span Assessment in the African Turquoise Killifish Nothobranchius furzeri.

The African turquoise killifish (Nothobranchius furzeri) is the shortest-lived vertebrate bred in captivity, with a median life span of 4-6 mo. Within its short life span, the killifish recapitulates critical aspects of human aging, including neurodegeneration and increased frailty. Developing standardized protocols for life span assessment in killifish is critical for identifying environmental and genetic factors that impact vertebrate life span. A standardized life span protocol should have low variability and high reproducibility, and it should enable comparison of life spans between laboratories. Here, we report our standardized protocol for measuring life span in the African turquoise killifish.

Husbandry of the African Turquoise Killifish Nothobranchius furzeri.

The African turquoise killifish (Nothobranchius furzeri) is an extremely short-lived vertebrate that has emerged as a powerful model organism for several research areas, including aging and embryonic diapause, which is the temporary suspension of embryonic development. The killifish research community is expanding and developing new solutions to improve the tractability of the killifish as a model system. Starting a killifish colony from scratch can present numerous challenges. In this protocol, we aim to highlight critical elements in building and maintaining a killifish colony. This protocol should help laboratories start a killifish colony and standardize aspects of killifish husbandry.

KidzMed e-learning to upskill student pharmacists to teach pill swallowing to children.

BACKGROUND: Appropriate medication use is essential in ensuring optimal pharmacotherapeutic outcomes. It is mistakenly assumed that adults can swallow solid oral dosage forms (SODFs, e.g. tablets/capsules colloquially referred to as 'pills'), without difficulty and that children cannot. KidzMed is a 'pill swallowing' training programme designed to teach effective SODF use in patients of all ages. It may be utilised by healthcare professionals to assist patients taking SODFs. E-learning was essential for training during COVID pandemic to reduce viral transmission. The aim of this study was to explore UK student pharmacists views of e-learning to support swallowing solid oral dosage forms. METHODS: This study used pre- and post-intervention online surveys on Microsoft Forms to evaluate self-directed eLearning about pill swallowing on MPharm programmes at three UK Universities using a 13-item survey. A combination of five-point Likert Scales and free-text items were used. The eLearning was available via the virtual learning environment at the University and embedded within existing curriculum. Descriptive statistical analysis was used to explore responses. RESULTS: In total, 113 of 340 (33%) students completed the survey. Seventy-eight percent (n = 65) reported the eLearning would enable them to teach adults and children to swallow SODFs successfully. Learners either agreed or strongly agreed that they felt comfortable to teach patients (95%, n = 62/113) and parents or carers (94%, n = 60) to swallow medications having completed the e-learning. Student pharmacists generally found eLearning as an acceptable way to reflect on their own experiences of 'pill' swallowing and how to support patients to swallow SODFs. CONCLUSION: The KidzMed eLearning was well received by student pharmacists. Further work is needed to explore whether skills translates into real life application in the clinical settings.

Dorsal attention network activity during perceptual organization is distinct in schizophrenia and predictive of cognitive disorganization.

Visual shape completion is a canonical perceptual organization process that integrates spatially distributed edge information into unified representations of objects. People with schizophrenia show difficulty in discriminating completed shapes, but the brain networks and functional connections underlying this perceptual difference remain poorly understood. Also unclear is whether brain network differences in schizophrenia occur in related illnesses or vary with illness features transdiagnostically. To address these topics, we scanned (functional magnetic resonance imaging, fMRI) people with schizophrenia, bipolar disorder, or no psychiatric illness during rest and during a task in which they discriminated configurations that formed or failed to form completed shapes (illusory and fragmented condition, respectively). Multivariate pattern differences were identified on the cortical surface using 360 predefined parcels and 12 functional networks composed of such parcels. Brain activity flow mapping was used to evaluate the likely involvement of resting-state connections for shape completion. Illusory/fragmented task activation differences ('modulations') in the dorsal attention network (DAN) could distinguish people with schizophrenia from the other groups (AUCs > .85) and could transdiagnostically predict cognitive disorganization severity. Activity flow over functional connections from the DAN could predict secondary visual network modulations in each group, except in schizophrenia. The secondary visual network was strongly and similarly modulated in each group. Task modulations were dispersed over more networks in patients compared to controls. In summary, DAN activity during visual perceptual organization is distinct in schizophrenia, symptomatically relevant, and potentially related to improper attention-related feedback into secondary visual areas.

Network modeling of dynamic brain interactions predicts emergence of neural information that supports human cognitive behavior.

How cognitive task behavior is generated by brain network interactions is a central question in neuroscience. Answering this question calls for the development of novel analysis tools that can firstly capture neural signatures of task information with high spatial and temporal precision (the "where and when") and then allow for empirical testing of alternative network models of brain function that link information to behavior (the "how"). We outline a novel network modeling approach suited to this purpose that is applied to noninvasive functional neuroimaging data in humans. We first dynamically decoded the spatiotemporal signatures of task information in the human brain by combining MRI-individualized source electroencephalography (EEG) with multivariate pattern analysis (MVPA). A newly developed network modeling approach-dynamic activity flow modeling-then simulated the flow of task-evoked activity over more causally interpretable (relative to standard functional connectivity [FC] approaches) resting-state functional connections (dynamic, lagged, direct, and directional). We demonstrate the utility of this modeling approach by applying it to elucidate network processes underlying sensory-motor information flow in the brain, revealing accurate predictions of empirical response information dynamics underlying behavior. Extending the model toward simulating network lesions suggested a role for the cognitive control networks (CCNs) as primary drivers of response information flow, transitioning from early dorsal attention network-dominated sensory-to-response transformation to later collaborative CCN engagement during response selection. These results demonstrate the utility of the dynamic activity flow modeling approach in identifying the generative network processes underlying neurocognitive phenomena.

Trends and Distribution of Political Contributions from Ophthalmologists in the United States.

PURPOSE: To describe the magnitude, party affiliation, temporal trend, and geographic distribution of political contributions made by ophthalmologists in the United States. METHODS: This cross-sectional study used public finance data from the Federal Election Commission website to identify political donations from ophthalmologists between 2003-2019. Contributions were filtered for occupation lines matching either "ophthalmologist," or "eye surgeon," and each contribution was cross-referenced to catalogue donations as "Republican," "Democratic," or "Independent." RESULTS: From 2003-2019, a total of 31,855 political donations were made by self-identified ophthalmologists, totaling $11,603,672. Of all dollars, 10.7%, 19.5%, and 69.8% went to Democratic, Republican, and Independent committees, respectively. Political contributions directed towards the American Academy of Ophthalmology Political Action Committee (OPHTHPAC) constituted the majority (59.8%) of overall contributions. From 2003 to 2019, the total number of unique contributions increased significantly from 1135 to 3208 (? = 0.63; P < .01). In dollars, this translated to an increase from $482,300 donated in 2003 to $640,695 donated in 2019, although this trend was non-significant (? = 0.18; P = .48). Conversely, the average amount of each contribution significantly declined from $425 to $203 (? = -0.35; P < .001). As expected, larger states such as California, Texas, Florida, Illinois, Michigan, and New York had the highest contribution dollars, in that order. CONCLUSIONS: Political contributions from ophthalmologists have significantly risen since 2003, however there remain opportunities for growth in engagement with OPHTHPAC. Future analysis of how this involvement translates to representative health policy is warranted.

The solution structures and relative stability constants of lanthanide-EDTA complexes predicted from computation.

Ligand selectivity to specific lanthanide (Ln) ions is key to the separation of rare earth elements from each other. Ligand selectivity can be quantified with relative stability constants (measured experimentally) or relative binding energies (calculated computationally). The relative stability constants of EDTA (ethylenediaminetetraacetic acid) with La3+, Eu3+, Gd3+, and Lu3+ were predicted from relative binding energies, which were quantified using electronic structure calculations with relativistic effects and based on the molecular structures of Ln-EDTA complexes in solution from density functional theory molecular dynamics simulations. The protonation state of an EDTA amine group was varied to study pH ∼7 and ∼11 conditions. Further, simulations at 25 °C and 90 °C were performed to elucidate how structures of Ln-EDTA complexes varying with temperature are related to complex stabilities at different pH conditions. Relative stability trends are predicted from computation for varying Ln3+ ions (La, Eu, Gd, Lu) with a single ligand (EDTA at pH ∼11), as well as for a single Ln3+ ion (La) with varying ligands (EDTA at pH ∼7 and ∼11). Changing the protonation state of an EDTA amine site significantly changes the solution structure of the Ln-EDTA complex resulting in a reduction of the complex stability. Increased Ln-ligand complex stability is correlated to reduced structural variations in solution upon an increase in temperature.

Oral Nutritional Supplementation Improves Growth in Children at Malnutrition Risk and with Picky Eating Behaviors.

The problem of poor nutrition with impaired growth persists in young children worldwide, including in India, where wasting occurs in 20% of urban children (<5 years). Exacerbating this problem, some children are described by their parent as a picky eater with behaviors such as eating limited food and unwillingness to try new foods. Timely intervention can help prevent nutritional decline and promote growth recovery; oral nutritional supplements (ONS) and dietary counseling (DC) are commonly used. The present study aimed to determine the effects of ONS along with DC on growth in comparison with the effects of DC only. Enrolled children (N = 321) were >24 to ≤48 months old, at malnutrition risk (weight-for-height percentile 3rd to 15th), and described as a picky eater by their parent. Enrollees were randomized to one of the three groups (N = 107 per group): ONS1 + DC; ONS2 + DC; and DC only. From day 1 to day 90, study findings showed significant increases in weight-for-height percentile for ONS1 + DC and for ONS2 + DC interventions, as compared to DC only (p = 0.0086 for both). There was no significant difference between the two ONS groups. Anthropometric measurements (weight and body mass index) also increased significantly over time for the two ONS groups (versus DC only, p < 0.05), while ONS1 + DC significantly improved mid-upper-arm circumference (p < 0.05 versus DC only), as well. ONS groups showed a trend toward greater height gain when compared to DC only group, but the differences were not significant within the study interval. For young Indian children with nutritional risk and picky eating behaviors, our findings showed that a 90-day nutritional intervention with either ONS1 or ONS2, along with DC, promoted catch-up growth more effectively than did DC alone.

Activity flow underlying abnormalities in brain activations and cognition in schizophrenia.

Cognitive dysfunction is a core feature of many brain disorders, including schizophrenia (SZ), and has been linked to aberrant brain activations. However, it is unclear how these activation abnormalities emerge. We propose that aberrant flow of brain activity across functional connectivity (FC) pathways leads to altered activations that produce cognitive dysfunction in SZ. We tested this hypothesis using activity flow mapping, an approach that models the movement of task-related activity between brain regions as a function of FC. Using functional magnetic resonance imaging data from SZ individuals and healthy controls during a working memory task, we found that activity flow models accurately predict aberrant cognitive activations across multiple brain networks. Within the same framework, we simulated a connectivity-based clinical intervention, predicting specific treatments that normalized brain activations and behavior in patients. Our results suggest that dysfunctional task-evoked activity flow is a large-scale network mechanism contributing to cognitive dysfunction in SZ.

Structural MRI and functional connectivity features predict current clinical status and persistence behavior in prescription opioid users.

Prescription opioid use disorder (POUD) has reached epidemic proportions in the United States, raising an urgent need for diagnostic biological tools that can improve predictions of disease characteristics. The use of neuroimaging methods to develop such biomarkers have yielded promising results when applied to neurodegenerative and psychiatric disorders, yet have not been extended to prescription opioid addiction. With this long-term goal in mind, we conducted a preliminary study in this understudied clinical group. Univariate and multivariate approaches to distinguishing between POUD (n = 26) and healthy controls (n = 21) were investigated, on the basis of structural MRI (sMRI) and resting-state functional connectivity (restFC) features. Univariate approaches revealed reduced structural integrity in the subcortical extent of a previously reported addiction-related network in POUD subjects. No reliable univariate between-group differences in cortical structure or edgewise restFC were observed. Contrasting these mixed univariate results, multivariate machine learning classification approaches recovered more statistically reliable group differences, especially when sMRI and restFC features were combined in a multi-modal model (classification accuracy = 66.7%, p < .001). The same multivariate multi-modal approach also yielded reliable prediction of individual differences in a clinically relevant behavioral measure (persistence behavior; predicted-to-actual overlap r = 0.42, p = .009). Our findings suggest that sMRI and restFC measures can be used to reliably distinguish the neural effects of long-term opioid use, and that this endeavor numerically benefits from multivariate predictive approaches and multi-modal feature sets. This can serve as theoretical proof-of-concept for future longitudinal modeling of prognostic POUD characteristics from neuroimaging features, which would have clearer clinical utility.

Brain network mechanisms of visual shape completion.

Visual shape completion recovers object shape, size, and number from spatially segregated edges. Despite being extensively investigated, the process's underlying brain regions, networks, and functional connections are still not well understood. To shed light on the topic, we scanned (fMRI) healthy adults during rest and during a task in which they discriminated pac-man configurations that formed or failed to form completed shapes (illusory and fragmented condition, respectively). Task activation differences (illusory-fragmented), resting-state functional connectivity, and multivariate patterns were identified on the cortical surface using 360 predefined parcels and 12 functional networks composed of such parcels. Brain activity flow mapping (ActFlow) was used to evaluate the likely involvement of resting-state connections for shape completion. We identified 36 differentially-active parcels including a posterior temporal region, PH, whose activity was consistent across 95% of observers. Significant task regions primarily occupied the secondary visual network but also incorporated the frontoparietal, dorsal attention, default mode, and cingulo-opercular networks. Each parcel's task activation difference could be modeled via its resting-state connections with the remaining parcels (r=.62, p<10-9), suggesting that such connections undergird shape completion. Functional connections from the dorsal attention network were key in modelling task activation differences in the secondary visual network. Dorsal attention and frontoparietal connections could also model activations in the remaining networks. Taken together, these results suggest that shape completion relies upon a sparsely distributed but densely interconnected network coalition that is centered in the secondary visual network, coordinated by the dorsal attention network, and inclusive of at least three other networks.

Acclimation potential of Noni (Morinda citrifolia L.) plant to temperature stress is mediated through photosynthetic electron transport rate.

Noni (Morindacitrifolia L.), a tropical, medicinal plant of the family Rubiaceae utilized since 2000 y ago by the Polynesians, is currently facing a major challenge in production vis-a-vis climate change. The worldwide average temperatures continue to fluctuate, resulting in extremely cold winters and hot summers that reduce plant productivity. Photosynthetic apparatus is an exceptionally sensitive component to estimate the degree of damage at contrasting temperatures. The present study was aimed to evaluate the temperature stress response of Noni plant using the chlorophyll a fluorescence OJIP transients (OJIP transients). Results showed the declined photosynthetic pigment pool and reduced functional and structural integrity of the photosynthetic apparatus under very low- and high-temperature treatments. Drastically lower yield parameters such as φ(Po) and φ(Eo), efficiency ψ(Eo) and performance indices - PIabs and PItotal, and accumulation of inactive reaction centers were observed. Consecutively, a lower level of calculated electron transport from PSII to PSI was observed. In contrast, the enhanced δRo indicates that PSI is more thermo-tolerant as compared to PSII. Additionally, very low and high temperatures cause an increase in antenna size (ABS/RC) and the decrease in the amplitude of I to P phase of fluorescence transient. Overall, the photosynthetic apparatus of leaf tissue was more sensitive to low and high temperatures than the developing fruit. The findings of the present study demonstrated the potential role of thylakoid components of the photosynthetic apparatus, which might be crucial in regulating the temperature stress response in the Noni plant, and thereby crop improvement.