Fetal alcohol spectrum disorder (FASD), caused by gestational ethanol (EtOH) exposure, is one of the most common causes of non-heritable and life-long mental disability worldwide, with no standard treatment or therapy available. While EtOH exposure can alter the function of both neurons and glia, it is still unclear how EtOH influences brain development to cause deficits in sensory and cognitive processing later in life. Microglia play an important role in shaping synaptic function and plasticity during neural circuit development and have been shown to mount an acute immunological response to EtOH exposure in certain brain regions. Therefore, we hypothesized that microglial roles in the healthy brain could be permanently altered by early EtOH exposure leading to deficits in experience-dependent plasticity. We used a mouse model of human third trimester high binge EtOH exposure, administering EtOH twice daily by subcutaneous injections from postnatal day 4 through postnatal day 9 (P4-:P9). Using a monocular deprivation model to assess ocular dominance plasticity, we found an EtOH-induced deficit in this type of visually driven experience-dependent plasticity. However, using a combination of immunohistochemistry, confocal microscopy, and in vivo two-photon microscopy to assay microglial morphology and dynamics, as well as fluorescence activated cell sorting (FACS) and RNA-seq to examine the microglial transcriptome, we found no evidence of microglial dysfunction in early adolescence. We also found no evidence of microglial activation in visual cortex acutely after early ethanol exposure, possibly because we also did not observe EtOH-induced neuronal cell death in this brain region. We conclude that early EtOH exposure caused a deficit in experience-dependent synaptic plasticity in the visual cortex that was independent of changes in microglial phenotype or function. This demonstrates that neural plasticity can remain impaired by developmental ethanol exposure even in a brain region where microglia do not acutely assume nor maintain an activated phenotype.

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Background Nonsuicidal self-injury (NSSI) is prevalent among adolescents and research is needed to clarify the mechanisms which contribute to the behavior. Here, the authors relate behavioral neurocognitive measures of impulsivity and compulsivity to repetitive and sporadic NSSI in a community sample of adolescents. Methods Computerized laboratory tasks (Affective Go/No-Go, Cambridge Gambling Task, and Probabilistic Reversal Task) were used to evaluate cognitive performance. Participants were adolescents aged 15 to 17 with (n = 50) and without (n = 190) NSSI history, sampled from the ROOTS project which recruited adolescents from secondary schools in Cambridgeshire, UK. NSSI was categorized as sporadic (1-3 instances per year) or repetitive (4 or more instances per year). Analyses were carried out in a series of linear and negative binomial regressions, controlling for age, gender, intelligence, and recent depressive symptoms. Results Adolescents with lifetime NSSI, and repetitive NSSI specifically, made significantly more perseverative errors on the Probabilistic Reversal Task and exhibited significantly lower quality of decision making on the Cambridge Gambling Task compared to no-NSSI controls. Those with sporadic NSSI did not significantly differ from no-NSSI controls on task performance. NSSI was not associated with behavioral measures of impulsivity. Conclusions Repetitive NSSI is associated with increased behavioral compulsivity and disadvantageous decision making, but not with behavioral impulsivity. Future research should continue to investigate how neurocognitive phenotypes contribute to the onset and maintenance of NSSI, and determine whether compulsivity and addictive features of NSSI are potential targets for treatment.

Background Invasive mechanical ventilation (IMV) is a standard therapy for intensive care patients with respiratory failure. With increasing population age and multimorbidity, the number of patients who cannot be weaned from IMV increases, resulting in impaired quality of life and high costs. In addition, human resources are tied up in the care of these patients. Methods The PRiVENT intervention is a prospective, mixed-methods interventional, multicentre study with a parallel comparison group selected from insurance claims data of the health insurer Allgemeine Ortskrankenkasse Baden-Württemberg (AOK-BW) conducted in Baden-Württemberg, Germany, over 24 months. Four weaning centres supervise 40 intensive care units (ICUs), that are responsible for patient recruitment. The primary outcome, successful weaning from IMV, will be evaluated using a mixed logistic regression model. Secondary outcomes will be evaluated using mixed regression models. Discussion The overall objective of the PRiVENT project is the evaluation of strategies to prevent long-term IMV. Additional objectives aim to improve weaning expertise in and cooperation with the adjacent Intensive Care Units. Trial registration This study is registered at ClinicalTrials.gov (NCT05260853).

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ObjectiveFew studies have investigated the neurological underpinnings of social-emotional processing among individuals with non-suicidal self-injury (NSSI), despite the range of interpersonal impairments associated with the behavior. This study aims to identify NSSI-specific patterns of resting state functional connectivity (RSFC) and neural activation during an emotional facial expression task.MethodsParticipants were currently depressed, antidepressant-free adolescents with and without lifetime history of NSSI. Left and right amygdala were specified as seed regions for RSFC analysis (n=43 NSSI, n=9 clinical controls). The emotional faces task presented participants with neutral, happy, and sad faces. Whole-brain analyses examined neural activation during the task, and groups were compared on post-scan ratings of facial emotional intensity (n=39 NSSI, n=9 clinical controls).ResultsGroups did not differ in RSFC analyses. Adolescents with NSSI showed attenuated neural activation to happy (versus neutral) faces in areas of the occipital lobe and cerebellum, and rated neutral and sad faces as more negative than clinical controls.ConclusionsWhile groups did not differ in baseline limbic connectivity, neurological and behavioral findings revealed NSSI-specific alterations in processing of social-emotional stimuli. Depressed adolescents with NSSI interpreted ambiguous or negative social stimuli more negatively than depressed controls, and had an attenuated neural response to positive social stimuli. This negative bias likely contributes to the myriad interpersonal difficulties associated with NSSI. Adolescents with NSSI may benefit from treatments which combat these negative social interpretations and improve control over emotional responses to interpersonal stress.

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