Large-scale analysis reveals racial disparities in the prevalence of ADHD and conduct disorders.

The primary purpose of this study is to highlight trends in the prevalence of attention deficit/hyperactivity disorders (ADHD) and conduct disorders (CD) between non-Hispanic White and non-Hispanic Black populations and identify potential diagnostic disparities between these groups. De-identified electronic health record data on the TriNetX platform of patients diagnosed with ADHD, CD, or both between January 2013 and May 2023 from 50 healthcare organizations in the US were used to investigate racial and sex disparities in the prevalence of ADHD and CD diagnoses. With a cohort of 849,281 ADHD patients and 157,597 CD patients, non-Hispanic White individuals were ~ 26% more likely to receive ADHD diagnosis and ~ 61% less likely to be diagnosed with CD than non-Hispanic Black individuals.

Zooming in on what counts as core and auxiliary: A case study on recognition models of visual working memory.

Research on best practices in theory assessment highlights that testing theories is challenging because they inherit a new set of assumptions as soon as they are linked to a specific methodology. In this article, we integrate and build on this work by demonstrating the breadth of these challenges. We show that tracking auxiliary assumptions is difficult because they are made at different stages of theory testing and at multiple levels of a theory.

Cutting Through the Noise: Auditory Scenes and Their Effects on Visual Object Processing.

Despite the intuitive feeling that our visual experience is coherent and comprehensive, the world is full of ambiguous and indeterminate information. Here we explore how the visual system might take advantage of ambient sounds to resolve this ambiguity. Young adults (s = 20-30) were tasked with identifying an object slowly fading in through visual noise while a task-irrelevant sound played.

Lipid clinic experience with bempedoic acid in three UK centres.

Objective: Novel lipid-lowering therapies are being introduced. Few studies exist of the real-world effectiveness of adenosine-tri-phosphate citrate lyase inhibition with bempedoic acid.

Methods: This study audited bempedoic acid therapy in 216 consecutive patients from three hospital centres - a university hospital ( = 77) and two district general hospitals ( = 106 and 33).

Longitudinal characterization of behavioral, morphological and transcriptomic changes in a tauopathy mouse model.

Neurodegenerative disorders, such as Alzheimer's disease (AD), have the gradual onset of neurobiological changes preceding clinical diagnosis by decades. To elucidate how brain dysfunction proceeds in neurodegenerative disorders, we performed longitudinal characterization of behavioral, morphological, and transcriptomic changes in a tauopathy mouse model, P301S transgenic mice. P301S mice exhibited cognitive deficits as early as 3 months old, and deficits in social preference and social cognition at 5-6 months.

There Is no Theory-Free Measure of "Swaps" in Visual Working Memory Experiments.

Visual working memory is highly limited, and its capacity is tied to many indices of cognitive function. For this reason, there is much interest in understanding its architecture and the sources of its limited capacity. As part of this research effort, researchers often attempt to decompose visual working memory errors into different kinds of errors, with different origins.

Inhibition of histone methyltransferase Smyd3 rescues NMDAR and cognitive deficits in a tauopathy mouse model.

Pleiotropic mechanisms have been implicated in Alzheimer's disease (AD), including transcriptional dysregulation, protein misprocessing and synaptic dysfunction, but how they are mechanistically linked to induce cognitive deficits in AD is unclear. Here we find that the histone methyltransferase Smyd3, which catalyzes histone H3 lysine 4 trimethylation (H3K4me3) to activate gene transcription, is significantly elevated in prefrontal cortex (PFC) of AD patients and P301S Tau mice, a model of tauopathies. A short treatment with the Smyd3 inhibitor, BCI-121, rescues cognitive behavioral deficits, and restores synaptic NMDAR function and expression in PFC pyramidal neurons of P301S Tau mice.

Measuring memory is harder than you think: How to avoid problematic measurement practices in memory research.

We argue that critical areas of memory research rely on problematic measurement practices and provide concrete suggestions to improve the situation. In particular, we highlight the prevalence of memory studies that use tasks (like the "old/new" task: "have you seen this item before? yes/no") where quantifying performance is deeply dependent on counterfactual reasoning that depends on the (unknowable) distribution of underlying memory signals. As a result of this difficulty, different literatures in memory research (e.

You cannot "count" how many items people remember in visual working memory: The importance of signal detection-based measures for understanding change detection performance.

Change detection tasks are commonly used to measure and understand the nature of visual working memory capacity. Across three experiments, we examine whether the nature of the memory signals used to perform change detection are continuous or all-or-none and consider the implications for proper measurement of performance. In Experiment 1, we find evidence from confidence reports that visual working memory is continuous in strength, with strong support for an equal variance signal detection model with no guesses or lapses.

What You See Is What You Hear: Sounds Alter the Contents of Visual Perception.

Visual object recognition is not performed in isolation but depends on prior knowledge and context. Here, we found that auditory context plays a critical role in visual object perception. Using a psychophysical task in which naturalistic sounds were paired with noisy visual inputs, we demonstrated across two experiments (young adults; s = 18-40 in Experiments 1 and 2, respectively) that the representations of ambiguous visual objects were shifted toward the visual features of an object that were related to the incidental sound.

EGR3 regulates opioid-related nociception and motivation in male rats.

Chronic pain can be a debilitating condition, leading to profound changes in nearly every aspect of life. However, the reliance on opioids such as oxycodone for pain management is thought to initiate dependence and addiction liability. The neurobiological intersection at which opioids relieve pain and possibly transition to addiction is poorly understood.

A convergent mechanism of high risk factors ADNP and POGZ in neurodevelopmental disorders.

ADNP and POGZ are two top-ranking risk factors for autism spectrum disorder and intellectual disability, but how they are linked to these neurodevelopmental disorders is largely unknown. Both ADNP and POGZ are chromatin regulators, which could profoundly affect gene transcription and cellular function in the brain. Using post-mortem tissue from patients with autism spectrum disorder, we found diminished expression of ADNP and POGZ in the prefrontal cortex, a region highly implicated in neurodevelopmental disorders.

When did that happen? The dynamic unfolding of perceived musical narrative.

People readily imagine narratives in response to instrumental music. Although previous work has established that these narratives show broad intersubjectivity, it remains unclear whether these imagined stories are atemporal, or unfold systematically over the temporal extent of a musical excerpt. To investigate the dynamics of perceived musical narrative, we had participants first listen to 16 instrumental musical excerpts, which had previously been normed for factors of interest.

Targeting histone demethylase LSD1 for treatment of deficits in autism mouse models.

Large-scale genetic studies have revealed that the most prominent genes disrupted in autism are chromatin regulators mediating histone methylation/demethylation, suggesting the central role of epigenetic dysfunction in this disorder. Here, we show that histone lysine 4 dimethylation (H3K4me2), a histone mark linked to gene activation, is significantly decreased in the prefrontal cortex (PFC) of autistic human patients and mutant mice with the deficiency of top-ranking autism risk factor Shank3 or Cul3. A brief treatment of the autism models with highly potent and selective inhibitors of the H3K4me2 demethylase LSD1 (KDM1A) leads to the robust rescue of core symptoms of autism, including social deficits and repetitive behaviors.

Clinical Features and Changes in Insulin Requirements in People with Type 2 Diabetes Requiring Insulin When Hospitalised with SARS-CoV-2 Infection.

Background: Uncontrolled hyperglycaemia before and during hospitalisation is a risk factor for adverse outcomes in people with diabetes and SARS-CoV-2 infection. Insulin often at high doses is frequently required to manage hyperglycaemia associated with SARS-CoV-2 infection during hospitalisation. However, there is limited information on the clinical features and sequelae of people with type 2 diabetes (T2DM) not previously on insulin that require insulin as a new treatment when hospitalised with SARS-CoV-2 infection.

Guidance of attention by working memory is a matter of representational fidelity.

Items that are held in visual working memory can guide attention toward matching features in the environment. Predominant theories propose that to guide attention, a memory item must be internally prioritized and given a special template status, which builds on the assumption that there are qualitatively distinct states in working memory. Here, we propose that no distinct states in working memory are necessary to explain why some items guide attention and others do not.

High-Order Areas and Auditory Cortex Both Represent the High-Level Event Structure of Music.

Recent fMRI studies of event segmentation have found that default mode regions represent high-level event structure during movie watching. In these regions, neural patterns are relatively stable during events and shift at event boundaries. Music, like narratives, contains hierarchical event structure (e.

Deficiency of autism risk factor ASH1L in prefrontal cortex induces epigenetic aberrations and seizures.

ASH1L, a histone methyltransferase, is identified as a top-ranking risk factor for autism spectrum disorder (ASD), however, little is known about the biological mechanisms underlying the link of ASH1L haploinsufficiency to ASD. Here we show that ASH1L expression and H3K4me3 level are significantly decreased in the prefrontal cortex (PFC) of postmortem tissues from ASD patients. Knockdown of Ash1L in PFC of juvenile mice induces the downregulation of risk genes associated with ASD, intellectual disability (ID) and epilepsy.

Epigenetic treatment of behavioral and physiological deficits in a tauopathy mouse model.

Epigenetic abnormality is implicated in neurodegenerative diseases associated with cognitive deficits, such as Alzheimer's disease (AD). A common feature of AD is the accumulation of neurofibrillary tangles composed of hyperphosphorylated tau. Transgenic mice expressing mutant P301S human tau protein develop AD-like progressive tau pathology and cognitive impairment.

Transcriptomic analysis of human brains with Alzheimer's disease reveals the altered expression of synaptic genes linked to cognitive deficits.

Alzheimer's disease is a progressive neurodegenerative disorder associated with memory loss and impaired executive function. The molecular underpinnings causing cognitive deficits in Alzheimer's disease are loosely understood. Here, we performed cross-study large-scale transcriptomic analyses of postmortem prefrontal cortex derived from Alzheimer's disease patients to reveal the role of aberrant gene expression in this disease.

Autism risk gene KMT5B deficiency in prefrontal cortex induces synaptic dysfunction and social deficits via alterations of DNA repair and gene transcription.

Large-scale genetic screening has identified KMT5B (SUV420H1), which encodes a histone H4 K20 di- and tri-methyltransferase highly expressed in prefrontal cortex (PFC), as a top-ranking high-risk gene for autism. However, the biological function of KMT5B in the brain is poorly characterized, and how KMT5B deficiency is linked to autism remains largely unknown. Here we knocked down Kmt5b in PFC and examined behavioral and electrophysiological changes, as well as underlying molecular mechanisms.

Working Memory: How Much Is It Used in Natural Behavior?

A new study suggests that visual working memory usage is interestingly low during a more naturalistic virtual reality paradigm, compared to capacity estimates from traditional lab studies. This raises new questions about the use of working memory in everyday tasks.

BrainIAK: The Brain Imaging Analysis Kit.

Functional magnetic resonance imaging (fMRI) offers a rich source of data for studying the neural basis of cognition. Here, we describe the Brain Imaging Analysis Kit (BrainIAK), an open-source, free Python package that provides computationally optimized solutions to key problems in advanced fMRI analysis. A variety of techniques are presently included in BrainIAK: intersubject correlation (ISC) and intersubject functional connectivity (ISFC), functional alignment via the shared response model (SRM), full correlation matrix analysis (FCMA), a Bayesian version of representational similarity analysis (BRSA), event segmentation using hidden Markov models, topographic factor analysis (TFA), inverted encoding models (IEMs), an fMRI data simulator that uses noise characteristics from real data (fmrisim), and some emerging methods.

Targeting histone K4 trimethylation for treatment of cognitive and synaptic deficits in mouse models of Alzheimer's disease.

Epigenetic aberration is implicated in aging and neurodegeneration. Using postmortem tissues from patients with Alzheimer's disease (AD) and AD mouse models, we have found that the permissive histone mark H3K4me3 and its catalyzing enzymes are significantly elevated in the prefrontal cortex (PFC). Inhibiting H3K4-specific methyltransferases with the compound WDR5-0103 leads to the substantial recovery of PFC synaptic function and memory-related behaviors in AD mice.

Reversal of synaptic and behavioral deficits in a 16p11.2 duplication mouse model via restoration of the GABA synapse regulator Npas4.

The human 16p11.2 gene locus is a hot spot for copy number variations, which predispose carriers to a range of neuropsychiatric phenotypes. Microduplications of 16p11.