Neuroglial interactions underpinning myelin plasticity.

The CNS is extremely responsive to an ever-changing environment. Studies of neural circuit plasticity focus almost exclusively on functional and structural changes of neuronal synapses. In recent years, however, myelin plasticity has emerged as a potential modulator of neuronal networks. Myelination of previously unmyelinated axons and changes in the structure of myelin on already-myelinated axons (similar to changes in internode number and length or myelin thickness or geometry of the nodal area) can in theory have significant effects on the function of neuronal networks. In this article, the authors review the current evidence for myelin changes occurring in the adult CNS, highlight some potential underlying mechanisms of how neuronal activity may regulate myelin changes, and explore the similarities between neuronal and myelin plasticity. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 93-107, 2018.We would like to thank our funders: Lister Institute of Preventive Medicine: Ragnhildur Thóra Káradóttir; Allen Distinguished Investigator programme, through The Paul G. Allen Frontiers Group: Ragnhildur Thóra Káradóttir and Kimberley Evans; Biotechnology and Biological Sciences Research Council (BBSRC) and The Cambridge Trust: E. A. Claudia Pama; UK Multiple Sclerosis Society: Ragnhildur Thóra Káradóttir and Omar de-Faria-jr, Award number 50. The funders had no role in decision to publish, or preparation of the manuscript

Early-life stress and inflammation: A systematic review of a key experimental approach in rodents

Repeated maternal separation is the most widely used pre-clinical approach to investigate the relationship between early-life chronic stress and its neuropsychiatric and physical consequences. In this systematic review, we identified 46 studies that conducted repeated maternal separation or single-episode maternal separation and reported measurements of interleukin-1b, interleukin-6, interleukin-10, tumour necrosis factor-alpha, or microglia activation and density. We report that in the short-term and in the context of later-life stress, repeated maternal separation has pro-inflammatory immune consequences in diverse tissues. Repeated maternal separation animals exhibit greater microglial activation and elevated pro-inflammatory cytokine signalling in key brain regions implicated in human psychiatric disorders. Notably, repeated maternal separation generally has no long-term effect on cytokine expression in any tissue in the absence of later-life stress. These observations suggest that the elevated inflammatory signalling that has been reported in humans with a history of early-life stress may be the joint consequence of ongoing stressor exposure together with potentiated neural and/or immune responsiveness to stressors. Finally, our findings provide detailed guidance for future studies interrogating the causal roles of early-life stress and inflammation in disorders such as major depression

Early-life stress biases responding to negative feedback and increases amygdala volume and vulnerability to later-life stress

Early-life stress (ELS) or adversity, particularly in the form of childhood neglect and abuse, is associated with poor mental and physical health outcomes in adulthood. However, whether these relationships are mediated by the consequences of ELS itself or by other exposures that frequently co-occur with ELS is unclear. To address this question, we carried out a longitudinal study in rats to isolate the effects of ELS on regional brain volumes and behavioral phenotypes relevant to anxiety and depression. We used the repeated maternal separation (RMS) model of chronic ELS, and conducted behavioral measurements throughout adulthood, including of probabilistic reversal learning (PRL), responding on a progressive ratio task, sucrose preference, novelty preference, novelty reactivity, and putative anxiety-like behavior on the elevated plus maze. Our behavioral assessment was combined with magnetic resonance imaging (MRI) for quantitation of regional brain volumes at three time points: immediately following RMS, young adulthood without further stress, and late adulthood with further stress. We found that RMS caused long-lasting, sexually dimorphic biased responding to negative feedback on the PRL task. RMS also slowed response time on the PRL task, but without this directly impacting task performance. RMS animals were also uniquely sensitive to a second stressor, which disproportionately impaired their performance and slowed their responding on the PRL task. MRI at the time of the adult stress revealed a larger amygdala volume in RMS animals compared with controls. These behavioral and neurobiological effects persisted well into adulthood despite a lack of effects on conventional tests of 'depression-like' and 'anxiety-like' behavior, and a lack of any evidence of anhedonia. Our findings indicate that ELS has long-lasting cognitive and neurobehavioral effects that interact with stress in adulthood and may have relevance for understanding the etiology of anxiety and depression in humans

Decision-making during the “Tweede Fase”: to what extent does this educational method correspond to the cognitive abilities of a child in the modern society?

 This article will discuss the conception of the modern child, and what society demands of him. Together, society’s conception and demands of children form the basis of the working model in an educational system. Specifically of interest in this article is a feature of the Dutch educational system, known as the "Tweede Fase". In this system, children are expected to make important decisions about their future, at a relatively young age. These decisions will likely exercise a decisive influence on the decisions they can make later in life, such as their choice of field of study. But are they really capable decision-makers at this point in their lives? What decisions do they make, and what choices do they have? What factors do they base their decisions on? These questions will be investigated from cognitive and neuroscientific perspectives, keeping in mind the realities of the developing brain. The present discussion will be based on Claessen’s article in this volume (2010). Some research suggests that certain skills which people need in order to make good decisions are not fully developed until young adulthood. Such information raises the question of whether a method like the "Tweede Fase" can be expected to be effective, given the actual cognitive abilities of young people in modern society

Exploring the relationship between cognitive development and educational programs

No abstrac

Multicentre evaluation of renal impairment in thoracic surgery (MERITS): a retrospective cohort study.

OBJECTIVES: To measure the unit-level variation in Acute Kidney Injury (AKI) incidence post-thoracic surgery over a contemporary 1-year period. Secondary aims include examining the associations with sex, age group, operation type, length of stay and mortality. DESIGN: A multicentre, observational, retrospective study in thoracic surgery. SETTING: 17 of 35 Society for Cardiothoracic Surgery of Great Britain and Ireland (SCTS) units participated. The student wing, known as SCTS STUDENTS, supported data collection. PARTICIPANTS: Overall, 15 229 patients were collected of which 15 154 were included for analysis after exclusions. All patients (age≥18 years) undergoing any thoracic surgery from 1 April 2016 to 31 March 2017 were included. For analysis, we excluded patients with preoperative end-stage renal failure and those with incomplete data. MAIN OUTCOME MEASURES: The primary outcome is the incidence of AKI within 7 days of the procedure or discharge date if earlier. Secondary outcomes include assessing associations with patient demographics (age, sex), type of procedure (open and minimally invasive), length of stay and mortality. RESULTS: Out of 15 154 patients AKI was diagnosed in 1090 patients (7.2%) within 7 days of surgery with AKI stage 1 (4.8%), stage 2 (1.7%) and stage 3 (0.7%). There was a statistically significant variation in AKI incidence between units from 3.1 to 16.1% (p<0.05). Significant differences between AKI and non-AKI were found in post-operative length of stay (7 vs 3 days, p<0.001), 30-day mortality (9 vs 1.6%, p<0.001), 90-day mortality (14.7 vs 4.4%, p<0.001) and 1-year mortality (23.1 vs 12.2 %, p<0.001). CONCLUSIONS: Following thoracic surgery, AKI incidence ranged from 3.1% to 16.1% between units (p<0.05) with associations between AKI and both length of stay and mortality. We propose AKI as a suitable comparative and absolute quality measure in thoracic surgery. Reducing rates of AKI may improve patient outcomes, length of stay and reduce costs

Sex-dependent effects of early life stress on reinforcement learning and limbic cortico-striatal functional connectivity.

Major depressive disorder (MDD) is a stress-related condition hypothesized to involve aberrant reinforcement learning (RL) with positive and negative stimuli. The present study investigated whether repeated early maternal separation (REMS) stress, a procedure widely recognized to cause depression-like behaviour, affects how subjects learn from positive and negative feedback. The REMS procedure was implemented by separating male and female rats from their dam for 6 h each day from post-natal day 5-19. Control rat offspring were left undisturbed during this period. Rats were tested as adults for behavioral flexibility and feedback sensitivity on a probabilistic reversal learning task. A computational approach based on RL theory was used to derive latent behavioral variables related to reward learning and flexibility. To assess underlying brain substrates, a seed-based functional MRI connectivity analysis was applied both before and after an additional adulthood stressor in control and REMS rats. Female but not male rats exposed to REMS stress showed increased response 'stickiness' (repeated responses regardless of reward outcome). Following repeated adulthood stress, reduced functional connectivity from the basolateral amygdala (BLA) to the dorsolateral striatum (DLS), cingulate cortex (Cg), and anterior insula (AI) cortex was observed in females. By contrast, control male rats exposed to the second stressor showed impaired learning from negative feedback (i.e., non-reward) and reduced functional connectivity from the BLA to the DLS and AI compared to maternally separated males. RL in male rats exposed to REMS was unaffected. The fMRI data further revealed that connectivity between the mOFC and other prefrontal cortical and subcortical structures was positively correlated with response 'stickiness'. These findings reveal differences in how females and males respond to early life adversity and subsequent stress. These effects may be mediated by functional divergence in resting-state connectivity between the basolateral amygdala and fronto-striatal brain regions

Early-life stress biases responding to negative feedback and increases amygdala volume and vulnerability to later-life stress.

Funder: EC | Erasmus+Early-life stress (ELS) or adversity, particularly in the form of childhood neglect and abuse, is associated with poor mental and physical health outcomes in adulthood. However, whether these relationships are mediated by the consequences of ELS itself or by other exposures that frequently co-occur with ELS is unclear. To address this question, we carried out a longitudinal study in rats to isolate the effects of ELS on regional brain volumes and behavioral phenotypes relevant to anxiety and depression. We used the repeated maternal separation (RMS) model of chronic ELS, and conducted behavioral measurements throughout adulthood, including of probabilistic reversal learning (PRL), responding on a progressive ratio task, sucrose preference, novelty preference, novelty reactivity, and putative anxiety-like behavior on the elevated plus maze. Our behavioral assessment was combined with magnetic resonance imaging (MRI) for quantitation of regional brain volumes at three time points: immediately following RMS, young adulthood without further stress, and late adulthood with further stress. We found that RMS caused long-lasting, sexually dimorphic biased responding to negative feedback on the PRL task. RMS also slowed response time on the PRL task, but without this directly impacting task performance. RMS animals were also uniquely sensitive to a second stressor, which disproportionately impaired their performance and slowed their responding on the PRL task. MRI at the time of the adult stress revealed a larger amygdala volume in RMS animals compared with controls. These behavioral and neurobiological effects persisted well into adulthood despite a lack of effects on conventional tests of 'depression-like' and 'anxiety-like' behavior, and a lack of any evidence of anhedonia. Our findings indicate that ELS has long-lasting cognitive and neurobehavioral effects that interact with stress in adulthood and may have relevance for understanding the etiology of anxiety and depression in humans

Early-life stress biases responding to negative feedback and increases amygdala volume and vulnerability to later-life stress.

Acknowledgements: The authors of this article are funded in part by a GSK Varsity Award (300034212), with core funding from the Medical Research Council (G1000183) and Wellcome Trust (093875/Z/10/Z) in support of the Behavioural and Clinical Neuroscience Institute at Cambridge University. EGD was supported by the Gates Cambridge Trust. ML was supported by a fellowship from the Medical Research Council (MR/S006257/1). MRC received support from the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, the NIHR Blood and Transplant Research Unit, a Medical Research Council New Investigator Research Grant (MR/N024907/1), an Arthritis Research UK Cure Challenge Research Grant (#21777), and an NIHR Research Professorship (RP-2017-08-ST2-002). ETB was supported by an NIHR Senior Investigator Award.Funder: EC | Erasmus+; doi: https://doi.org/10.13039/501100010790Early-life stress (ELS) or adversity, particularly in the form of childhood neglect and abuse, is associated with poor mental and physical health outcomes in adulthood. However, whether these relationships are mediated by the consequences of ELS itself or by other exposures that frequently co-occur with ELS is unclear. To address this question, we carried out a longitudinal study in rats to isolate the effects of ELS on regional brain volumes and behavioral phenotypes relevant to anxiety and depression. We used the repeated maternal separation (RMS) model of chronic ELS, and conducted behavioral measurements throughout adulthood, including of probabilistic reversal learning (PRL), responding on a progressive ratio task, sucrose preference, novelty preference, novelty reactivity, and putative anxiety-like behavior on the elevated plus maze. Our behavioral assessment was combined with magnetic resonance imaging (MRI) for quantitation of regional brain volumes at three time points: immediately following RMS, young adulthood without further stress, and late adulthood with further stress. We found that RMS caused long-lasting, sexually dimorphic biased responding to negative feedback on the PRL task. RMS also slowed response time on the PRL task, but without this directly impacting task performance. RMS animals were also uniquely sensitive to a second stressor, which disproportionately impaired their performance and slowed their responding on the PRL task. MRI at the time of the adult stress revealed a larger amygdala volume in RMS animals compared with controls. These behavioral and neurobiological effects persisted well into adulthood despite a lack of effects on conventional tests of 'depression-like' and 'anxiety-like' behavior, and a lack of any evidence of anhedonia. Our findings indicate that ELS has long-lasting cognitive and neurobehavioral effects that interact with stress in adulthood and may have relevance for understanding the etiology of anxiety and depression in humans