Neural Responses to Novel and Existing Words in Children with Autism Spectrum and Developmental Language Disorder

The formation of new phonological representations is key in establishing items in the mental lexicon. Phonological forms become stable with repetition, time and sleep. Atypicality in the establishment of new word forms is characteristic of children with developmental language disorder (DLD) and autism spectrum disorder (ASD), yet neural changes in response to novel word forms over time have not yet been directly compared in these groups. This study measured habituation of event-related-potentials (ERPs) to novel and known words within and between two sessions spaced 24 hours apart in typically developing (TD) children, and their peers with DLD or ASD. We hypothesised that modulation of the auditory N400 amplitude would mark real-time changes in lexical processing with habituation evident within and across sessions in the TD group, while the DLD group would show attenuated habituation within sessions, and the ASD group attenuated habituation between sessions. Twenty-one typically developing children, 19 children with ASD, and 16 children with DLD listened passively to known and novel words on two consecutive days, while ERPs were recorded using dry electrodes. Counter to our hypotheses, no habituation effect emerged within sessions. However, responses did habituate between sessions, with this effect being reduced in the DLD group, indicating less pre-activation of lexical representations in response to words encountered the previous day. No differences in change over time were observed between the TD and ASD groups. These data are in keeping with theories stressing the importance of sleep-related consolidation in word learning

A synergistic approach for evaluating climate model output for ecological applications

Increasing concern about the impacts of climate change on ecosystems is prompting ecologists and ecosystem managers to seek reliable projections of physical drivers of change. The use of global climate models in ecology is growing, although drawing ecologically meaningful conclusions can be problematic. The expertise required to access and interpret output from climate and earth system models is hampering progress in utilizing them most effectively to determine the wider implications of climate change. To address this issue, we present a joint approach between climate scientists and ecologists that explores key challenges and opportunities for progress. As an exemplar, our focus is the Southern Ocean, notable for significant change with global implications, and on sea ice, given its crucial role in this dynamic ecosystem. We combined perspectives to evaluate the representation of sea ice in global climate models. With an emphasis on ecologically-relevant criteria (sea ice extent and seasonality) we selected a subset of eight models that reliably reproduce extant sea ice distributions. While the model subset shows a similar mean change to the full ensemble in sea ice extent (approximately 50% decline in winter and 30% decline in summer), there is a marked reduction in the range. This improved the precision of projected future sea ice distributions by approximately one third, and means they are more amenable to ecological interpretation. We conclude that careful multidisciplinary evaluation of climate models, in conjunction with ongoing modeling advances, should form an integral part of utilizing model output

Towards a circuit-based understanding of neuropsychiatric disorders: circuit-specific contributions to major depressive disorder and addiction

Motivation directs and guides an organisms interaction with their environment and is profoundly influenced by internal brain states in conjunction with external environmental stimuli. Motivated behaviors can range from survival-based actions such as foraging for food or avoiding potentially deadly conflict to pursuit of pleasure or sex. Proper maintenance of every day motivation is essential for guiding behavior to preserve homeostatic balance and stable functioning. However, states of pathological motivation result when proper motivational control is lost. Instances of hyper-motivation misdirected towards harmful or negative stimuli can manifest as addiction, and conversely loss of motivation and extreme apathy is a hallmark of major depressive disorder (MDD). How then, does the brain regulate motivation and what kind of adaptations lead to conditions such as addiction and depression? Components of the reward circuitry in the brain such as the nucleus accumbens (NAc) has been heavily studied in the context of addiction and MDD. As a central node in the reward circuitry, the NAc receives dopaminergic input from the ventral tegmental area (VTA) in the midbrain and sends its primary output to the ventral pallidum (VP) and back to the VTA. While structural and electrophysiological changes in neurons within the NAc have been well described in addiction and MDD, much less is known how the NAc interacts with the reward circuitry as a whole. In particular, how do the various interconnections within the reward circuit relate to the complex behaviors characteristic of neuropsychiatric conditions such as MDD and addiction? This dissertation aims to shed light on how discrete aspects of circuits involving the NAc and VP contribute to discrete behavioral aspects of addiction and MDD. Chapter I illustrates that discrete components of the ventral pallidal circuit mediates separate depressive-like behaviors in a mouse model of depression. In chapter II, we outline discrete structural changes in separate input structures of the NAc at different stages of addiction. In all, this dissertation hopes to illuminate the circuit-specific changes governing neuropsychiatric disorders that may provide a platform for more specific treatments

Towards a circuit-based understanding of neuropsychiatric disorders: circuit-specific contributions to major depressive disorder and addiction

Motivation directs and guides an organisms interaction with their environment and is profoundly influenced by internal brain states in conjunction with external environmental stimuli. Motivated behaviors can range from survival-based actions such as foraging for food or avoiding potentially deadly conflict to pursuit of pleasure or sex. Proper maintenance of every day motivation is essential for guiding behavior to preserve homeostatic balance and stable functioning. However, states of pathological motivation result when proper motivational control is lost. Instances of hyper-motivation misdirected towards harmful or negative stimuli can manifest as addiction, and conversely loss of motivation and extreme apathy is a hallmark of major depressive disorder (MDD). How then, does the brain regulate motivation and what kind of adaptations lead to conditions such as addiction and depression? Components of the reward circuitry in the brain such as the nucleus accumbens (NAc) has been heavily studied in the context of addiction and MDD. As a central node in the reward circuitry, the NAc receives dopaminergic input from the ventral tegmental area (VTA) in the midbrain and sends its primary output to the ventral pallidum (VP) and back to the VTA. While structural and electrophysiological changes in neurons within the NAc have been well described in addiction and MDD, much less is known how the NAc interacts with the reward circuitry as a whole. In particular, how do the various interconnections within the reward circuit relate to the complex behaviors characteristic of neuropsychiatric conditions such as MDD and addiction? This dissertation aims to shed light on how discrete aspects of circuits involving the NAc and VP contribute to discrete behavioral aspects of addiction and MDD. Chapter I illustrates that discrete components of the ventral pallidal circuit mediates separate depressive-like behaviors in a mouse model of depression. In chapter II, we outline discrete structural changes in separate input structures of the NAc at different stages of addiction. In all, this dissertation hopes to illuminate the circuit-specific changes governing neuropsychiatric disorders that may provide a platform for more specific treatments

Distinct Ventral Pallidal Neural Populations Mediate Separate Symptoms of Depression

Major depressive disorder (MDD) patients display a common but often variable set of symptoms making successful, sustained treatment difficult to achieve. Separate depressive symptoms may be encoded by differential changes in distinct circuits in the brain, yet how discrete circuits underlie behavioral subsets of depression and how they adapt in response to stress has not been addressed. We identify two discrete circuits of parvalbumin-positive (PV) neurons in the ventral pallidum (VP) projecting to either the lateral habenula or ventral tegmental area contributing to depression. We find that these populations undergo different electrophysiological adaptations in response to social defeat stress, which are normalized by antidepressant treatment. Furthermore, manipulation of each population mediates either social withdrawal or behavioral despair, but not both. We propose that distinct components of the VP PV circuit can subserve related, yet separate depressive-like phenotypes in mice, which could ultimately provide a platform for symptom-specific treatments of depression

Impact of Stratosphere on Cold Air Outbreak: Observed Evidence by CrIS on SNPP and Its Comparison with Models

A cold air outbreak (CAO) is an extreme weather phenomenon that has significant social and economic impacts over a large region of the midlatitudes. However, the dynamical mechanism of the occurrence and evolution of CAO events, particularly the role of the stratosphere, is not well understood. Through an analysis of one extreme CAO episode that occurred on 27–31 January 2019 across much of the US Midwest, this study examined its thermodynamic structure and the impact of stratospheric downward transport using the single-field-view (SFOV) satellite products (with a spatial resolution of ~14 km at nadir) from the Cross-track Infrared Sounder (CrIS) onboard Suomi National Polar-Orbiting Partnership (SNPP) in conjunction with MERRA-2 and ERA-5 reanalysis products. It is found that along the path of cold air transport, particularly near the coldest surface center, there exists a large enhancement of O3, deep tropopause folding, significant downward transport of stratospheric dry air, and a warm center above the tropopause. The upper warm center can be observed directly using the brightness temperature (BT) of CrIS stratospheric sounding channels. While similar large-scale patterns of temperature (T), relative humidity (RH), and ozone (O3) are captured from CrIS, MERRA-2, and ERA-5 products, it is found that, in the regions impacted by CAO, MERRA-2 has a thicker dry layer under the tropopause (with the difference of RH up to ~10%) and the total column ozone (TCO) from ERA-5 has a relatively large positive bias of 2.8 ± 2.8% compared to that measured by Ozone Mapping and Profiler Suite (OMPS). This study provides some observational evidence from CrIS that confirm the impact of the stratosphere on CAO through downward transport and demonstrates the value of the SFOV retrieval products for CAO dynamic transport study and model evaluation

Functional α6β4 acetylcholine receptor expression enables pharmacological testing of nicotinic agonists with analgesic properties.

The α6β4 nicotinic acetylcholine receptor (nAChR) is enriched in dorsal root ganglia neurons and is an attractive non-opioid therapeutic target for pain. However, difficulty expressing human α6β4 receptors in recombinant systems has precluded drug discovery. Here, genome-wide screening identified accessory proteins that enable reconstitution of human α6β4 nAChRs. BARP, an auxiliary subunit of voltage-dependent calcium channels, promoted α6β4 surface expression while IRE1α, an unfolded protein response sensor, enhanced α6β4 receptor assembly. Effects on α6β4 involve BARPs N-terminal region and IRE1αs splicing of XBP1 mRNA. Furthermore, clinical efficacy of nicotinic agents in relieving neuropathic pain best correlated with their activity on α6β4. Finally, BARP-knockout, but not NACHO-knockout mice lacked nicotine-induced antiallodynia, highlighting the functional importance of α6β4 in pain. These results identify roles for IRE1α and BARP in neurotransmitter receptor assembly and unlock drug discovery for the previously elusive α6β4 receptor