Componential theories of lexical semantics assume that concepts can be represented by sets of features or attributes that are in some sense primitive or basic components of meaning. The binary ...features used in classical category and prototype theories are problematic in that these features are themselves complex concepts, leaving open the question of what constitutes a primitive feature. The present availability of brain imaging tools has enhanced interest in how concepts are represented in brains, and accumulating evidence supports the claim that these representations are at least partly "embodied" in the perception, action, and other modal neural systems through which concepts are experienced. In this study we explore the possibility of devising a componential model of semantic representation based entirely on such functional divisions in the human brain. We propose a basic set of approximately 65 experiential attributes based on neurobiological considerations, comprising sensory, motor, spatial, temporal, affective, social, and cognitive experiences. We provide normative data on the salience of each attribute for a large set of English nouns, verbs, and adjectives, and show how these attribute vectors distinguish a priori conceptual categories and capture semantic similarity. Robust quantitative differences between concrete object categories were observed across a large number of attribute dimensions. A within- versus between-category similarity metric showed much greater separation between categories than representations derived from distributional (latent semantic) analysis of text. Cluster analyses were used to explore the similarity structure in the data independent of a priori labels, revealing several novel category distinctions. We discuss how such a representation might deal with various longstanding problems in semantic theory, such as feature selection and weighting, representation of abstract concepts, effects of context on semantic retrieval, and conceptual combination. In contrast to componential models based on verbal features, the proposed representation systematically relates semantic content to large-scale brain networks and biologically plausible accounts of concept acquisition.
Abstract
Background
Patients with chronic illness are at increased risk for traumatic stress because of medical trauma. Initial studies of posttraumatic stress (PTS) in patients with inflammatory ...bowel disease (IBD) have found that approximately one-third of patients may experience significant PTS symptoms including flashbacks, nightmares, hypervigilance, disrupted sleep, and low mood. We aim to better characterize PTS in IBD and its relationship with patient outcomes in a large cohort of patients with IBD.
Methods
Adult patients registered with the Crohn’s & Colitis Foundation/University of North Carolina IBD Partners database were invited to complete a supplementary survey between February and July 2020. The Post Traumatic Stress Disorder Checklist-5th edition was administered as a supplemental survey. Additional data from IBD Partners included disease severity, surgery and hospital history, demographics, and health care utilization.
Results
A total of 797 patients participated (452 with Crohn disease, 345 with ulcerative colitis). No impacts on response patterns because of the COVID-19 pandemic were found. Although 5.6% of the sample reported an existing PTS diagnosis because of IBD experiences, 9.6% of participants met the full IBD-related PTS diagnostic criteria per the Post Traumatic Stress Disorder Checklist-5th edition. Female patients, younger patients, those with less educational attainment, non-White patients, and Hispanic patients reported higher levels of PTS symptoms. Patients with higher PTS symptoms were more likely to have been hospitalized, have had surgery, have more severe symptoms, and not be in remission. Increased PTS was also associated with increased anxiety, depression, pain interference, fatigue, and health care utilization.
Conclusions
The present findings support prior research that approximately one-quarter to one-third of patients with IBD report significant symptoms of PTS directly from their disease experiences, and certain demographic groups are at higher risk. In addition, PTS is associated with several IBD outcomes. Patients with higher PTS symptoms are less likely to be in remission and may utilize more outpatient gastrointestinal services. Intervention trials to mitigate PTS symptoms in patients with IBD are warranted.
Abstract
Electrophysiological sleep rhythms have been shown to impact human waking cognition, but their spatio-temporal dynamics are not understood. We investigated how slow oscillations (SOs; 0.5–4 ...Hz) are organized during a night of polysomnographically-recorded sleep, focusing on the scalp electrode manifold. We detected troughs of SOs at all electrodes independently and analyzed the concurrent SO troughs found in every other electrode within ±400 ms. We used a k-clustering algorithm to categorize the spatial patterns of SO trough co-occurrence into three types (Global, Local or Frontal) depending on their footprint on the electrode manifold during the considered time window. When comparing the clusters across non-rapid eye movement (NREM) sleep stages, we found a relatively larger fraction of Local SOs in slow wave sleep (SWS) compared to stage 2, and larger fraction of Global SOs in stage 2 compared to SWS. The probability of SO detection in time between two electrodes showed that SO troughs of all types co-occurred at some nearby electrodes, but only Global troughs had traveling wave profiles, moving anteriorly to posteriorly. Global SOs also had larger amplitudes at frontal electrodes and stronger coupling with fast spindles (12.5–16 Hz). Indeed, SO-spindle complexes were more likely to be detected following a Global SO trough compared to SOs in other clusters. Also, the phase-amplitude modulation of SOs over spindles (modulation vector) was higher for Global SOs across the electrode manifold. Given the recent evidence of a link between thalamocortical coupling and cognition, our findings suggest stronger cognitive relevance of Global SOs as compared to other SO types in sleep memory processing.
Clinical Trials
No clinical trial is related to this study.
Although much is known about the mechanisms underlying synaptic plasticity, the cellular mechanisms that negatively regulate plasticity in some brain regions are considerably less studied. One region ...where neurons do not reliably express long-term potentiation (LTP) is the CA2 subfield of the hippocampus. Given the connection between synaptic plasticity and increases in postsynaptic Ca²⁺, and that CA2 neurons express a large number of calcium-regulating proteins, we tested the hypothesis that the relative lack of LTP in CA2 results from differences in the calcium dynamics of these neurons. By measuring calcium-dependent fluorescence transients in dendritic spines, we show that CA2 neurons have smaller action potential-evoked intracellular Ca²⁺ transients because of a higher endogenous Ca²⁺-buffering capacity and significantly higher rates of Ca²⁺ extrusion when compared with CA1 and CA3 neurons. Perfusion with higher external Ca²⁺ during induction restores LTP to CA2 neurons, suggesting that they possess the cellular machinery required for plasticity, but that the restriction of postsynaptic Ca²⁺ limits its expression. Camstatin, an analogue of the calcium-modulating protein Pep-19 strongly expressed in CA2 neurons, blocked LTP and increased Ca²⁺ extrusion in CA1 neurons, suggesting a role for extrusion in the regulation of plasticity in CA2. In agreement with this idea, we found that intracellular introduction of a PMCA pump inhibitor (carboxyeosin) allows for the induction of LTP in CA2 neurons. Our results indicate that regulation of postsynaptic Ca²⁺ through modulation of extrusion and/or buffering regulates expression of LTP in CA2 and potentially other brain regions.
Learning and memory have been closely linked to strengthening of synaptic connections between neurons (i.e., synaptic plasticity) within the dentate gyrus (DG)—CA3—CA1 trisynaptic circuit of the ...hippocampus. Conspicuously absent from this circuit is area CA2, an intervening hippocampal region that is poorly understood. Schaffer collateral synapses on CA2 neurons are distinct from those on other hippocampal neurons in that they exhibit a perplexing lack of synaptic long-term potentiation (LTP). Here we demonstrate that the signaling protein RGS14 is highly enriched in CA2 pyramidal neurons and plays a role in suppression of both synaptic plasticity at these synapses and hippocampal-based learning and memory. RGS14 is a scaffolding protein that integrates G protein and H-Ras/ERK/MAP kinase signaling pathways, thereby making it well positioned to suppress plasticity in CA2 neurons. Supporting this idea, deletion of exons 2—7 of the RGS14 gene yields mice that lack RGS14 (RGS14-KO) and now express robust LTP at glutamatergic synapses in CA2 neurons with no impact on synaptic plasticity in CA1 neurons. Treatment of RGS14-deficient CA2 neurons with a specific MEK inhibitor blocked this LTP, suggesting a role for ERK/MAP kinase signaling pathways in this process. When tested behaviorally, RGS14-KO mice exhibited marked enhancement in spatial learning and in object recognition memory compared with their wild-type littermates, but showed no differences in their performance on tests of nonhippocampal-dependent behaviors. These results demonstrate that RGS14 is a key regulator of signaling pathways linking synaptic plasticity in CA2 pyramidal neurons to hippocampal-based learning and memory but distinct from the canonical DG—CA3—CA1 circuit.
Sounds associated with newly learned information that are replayed during non-rapid eye movement (NREM) sleep can improve recall in simple tasks. The mechanism for this improvement is presumed to be ...reactivation of the newly learned memory during sleep when consolidation takes place. We have developed an EEG-based closed-loop system to precisely deliver sensory stimulation at the time of down-state to up-state transitions during NREM sleep. Here, we demonstrate that applying this technology to participants performing a realistic navigation task in virtual reality results in a significant improvement in navigation efficiency after sleep that is accompanied by increases in the spectral power especially in the fast (12-15 Hz) sleep spindle band. Our results show promise for the application of sleep-based interventions to drive improvement in real-world tasks.
The creation of machine learning algorithms for intelligent agents capable of continuous, lifelong learning is a critical objective for algorithms being deployed on real-life systems in dynamic ...environments. Here we present an algorithm inspired by neuromodulatory mechanisms in the human brain that integrates and expands upon Stephen Grossberg’s ground-breaking Adaptive Resonance Theory proposals. Specifically, it builds on the concept of uncertainty, and employs a series of “neuromodulatory” mechanisms to enable continuous learning, including self-supervised and one-shot learning. Algorithm components were evaluated in a series of benchmark experiments that demonstrate stable learning without catastrophic forgetting. We also demonstrate the critical role of developing these systems in a closed-loop manner where the environment and the agent’s behaviors constrain and guide the learning process. To this end, we integrated the algorithm into an embodied simulated drone agent. The experiments show that the algorithm is capable of continuous learning of new tasks and under changed conditions with high classification accuracy (>94%) in a virtual environment, without catastrophic forgetting. The algorithm accepts high dimensional inputs from any state-of-the-art detection and feature extraction algorithms, making it a flexible addition to existing systems. We also describe future development efforts focused on imbuing the algorithm with mechanisms to seek out new knowledge as well as employ a broader range of neuromodulatory processes.
•Adaptive Resonance Theory architectures can solve the stability-plasticity dilemma.•Our self-supervised system, based on ART, exhibits lifelong learning capabilities.•We show an agent learn new objects and adapt to new circumstances in real-time.
Infantile hemangiomas (IHs) are the most common tumors of childhood. Unlike other tumors, they have the unique ability to involute after proliferation, often leading primary care providers to assume ...they will resolve without intervention or consequence. Unfortunately, a subset of IHs rapidly develop complications, resulting in pain, functional impairment, or permanent disfigurement. As a result, the primary clinician has the task of determining which lesions require early consultation with a specialist. Although several recent reviews have been published, this clinical report is the first based on input from individuals representing the many specialties involved in the treatment of IH. Its purpose is to update the pediatric community regarding recent discoveries in IH pathogenesis, treatment, and clinical associations and to provide a basis for clinical decision-making in the management of IH.
Transcranial electrical stimulation (tES) during sleep has been shown to successfully modulate memory consolidation. Here, we tested the effect of short duration repetitive tES (SDR-tES) during a ...daytime nap on the consolidation of declarative memory of facts in healthy individuals. We use a previously described approach to deliver the stimulation at regular intervals during non-rapid eye movement (NREM) sleep, specifically stage NREM2 and NREM3. Similar to previous studies using tES, we find enhanced memory performance compared to sham both after sleep and 48 h later. We also observed an increase in the proportion of time spent in NREM3 sleep and SDR-tES boosted the overall rate of slow oscillations (SOs) during NREM2/NREM3 sleep. Retrospective investigation of brain activity immediately preceding stimulation suggests that increases in the SO rate are more likely when stimulation is delivered during quiescent and asynchronous periods of activity in contrast to other closed-loop approaches which target phasic stimulation during ongoing SOs.
Australian Genomics is a national collaborative partnership of more than 100 organizations piloting a whole-of-system approach to integrating genomics into healthcare, based on federation principles. ...In the first five years of operation, Australian Genomics has evaluated the outcomes of genomic testing in more than 5,200 individuals across 19 rare disease and cancer flagship studies. Comprehensive analyses of the health economic, policy, ethical, legal, implementation and workforce implications of incorporating genomics in the Australian context have informed evidence-based change in policy and practice, resulting in national government funding and equity of access for a range of genomic tests. Simultaneously, Australian Genomics has built national skills, infrastructure, policy, and data resources to enable effective data sharing to drive discovery research and support improvements in clinical genomic delivery.
We describe outcomes of a 5-year national program to accelerate the implementation of genomics into healthcare. We evaluated genomic testing in more than 5,200 individuals across 19 rare disease and cancer flagship studies. Simultaneously, we built skills, infrastructure, policy, and data resources to drive discovery research and support clinical genomic delivery.
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