A vectorial code for semantics in human hippocampus.

As we listen to speech, our brains actively compute the meaning of individual words. Inspired by the success of large language models (LLMs), we hypothesized that the brain employs vectorial coding principles, such that meaning is reflected in distributed activity of single neurons. We recorded responses of hundreds of neurons in the human hippocampus, which has a well-established role in semantic coding, while participants listened to narrative speech.

Endocannabinoids facilitate transitory reward engagement through retrograde gain-control.

Neuromodulatory signaling is poised to serve as a neural mechanism for gain control, acting as a crucial tuning factor to influence neuronal activity by dynamically shaping excitatory and inhibitory fast neurotransmission. The endocannabinoid (eCB) signaling system, the most widely expressed neuromodulatory system in the mammalian brain, is known to filter excitatory and inhibitory inputs through retrograde, pre-synaptic action. However, whether eCBs exert retrograde gain control to ultimately facilitate reward-seeking behaviors in freely moving mammals is not established.

Dissociable roles of central striatum and anterior lateral motor area in initiating and sustaining naturalistic behavior.

Understanding how corticostriatal circuits mediate behavioral selection and initiation in a naturalistic setting is critical to understanding behavior choice and execution in unconstrained situations. The central striatum (CS) is well poised to play an important role in these spontaneous processes. Using fiber photometry and optogenetics, we identify a role for CS in grooming initiation.

Integrated electronic health record tools to access real-world data in oncology research.

Objectives: The Integrating Clinical Trials and Real-World Endpoints (ICAREdata) project aimed to demonstrate that electronic health record (EHR) data, expressed in a standard structured format, can be extracted and transmitted to contribute to clinical research. Using the minimal Common Oncology Data Elements (mCODE), we collected standardized oncology outcome data from EHRs across 10 clinical sites and 15 trials. This report details and assesses the ICAREdata technical implementation and offers recommendations to benefit future projects with similar goals.

Feasibility of structuring electronic health record data to facilitate real-world data research: ICAREdata methods applied to multicenter cancer clinical trials.

Background: The use of electronic health record (EHR) data for research is limited by a lack of structure and a standard data model. The objective of the ICAREdata (Integrating Clinical Trials and Real-World Endpoints Data) project was to structure key research data elements in EHRs using a minimal Common Oncology Data Elements (mCODE) data model to extract and transmit data.

Methods: The ICAREdata project captured two EHR data elements essential to clinical trials: cancer disease status and treatment plan change.

Continuous and discrete proportion elicit different cognitive strategies.

Despite proportional information being ubiquitous, there is not a standard account of proportional reasoning. Part of the difficulty is that there are several apparent contradictions: in some contexts, proportion is easy and privileged, while in others it is difficult and ignored. One possibility is that although we see similarities across tasks requiring proportional reasoning, people approach them with different strategies.

Symbolic metaprogram search improves learning efficiency and explains rule learning in humans.

Throughout their lives, humans seem to learn a variety of rules for things like applying category labels, following procedures, and explaining causal relationships. These rules are often algorithmically rich but are nonetheless acquired with minimal data and computation. Symbolic models based on program learning successfully explain rule-learning in many domains, but performance degrades quickly as program complexity increases.

Why concepts are (probably) vectors.

For decades, cognitive scientists have debated what kind of representation might characterize human concepts. Whatever the format of the representation, it must allow for the computation of varied properties, including similarities, features, categories, definitions, and relations. It must also support the development of theories, ad hoc categories, and knowledge of procedures.

Endogenous opioids facilitate stress-induced binge eating via an insular cortex-claustrum pathway.

Stress has been shown to promote the development and persistence of binge eating behaviors. However, the neural circuit mechanisms for stress-induced binge-eating behaviors are largely unreported. The endogenous dynorphin (dyn)/kappa opioid receptor (KOR) opioid neuropeptide system has been well established to be a crucial mediator of the anhedonic component of stress.

Language is primarily a tool for communication rather than thought.

Language is a defining characteristic of our species, but the function, or functions, that it serves has been debated for centuries. Here we bring recent evidence from neuroscience and allied disciplines to argue that in modern humans, language is a tool for communication, contrary to a prominent view that we use language for thinking. We begin by introducing the brain network that supports linguistic ability in humans.

Formalising the role of behaviour in neuroscience.

We develop a mathematical approach to formally proving that certain neural computations and representations exist based on patterns observed in an organism's behaviour. To illustrate, we provide a simple set of conditions under which an ant's ability to determine how far it is from its nest would logically imply neural structures isomorphic to the natural numbers . We generalise these results to arbitrary behaviours and representations and show what mathematical characterisation of neural computation and representation is simplest while being maximally predictive of behaviour.

An integrated microfluidic and fluorescence platform for probing in vivo neuropharmacology.

Neurotechnologies and genetic tools for dissecting neural circuit functions have advanced rapidly over the past decade, although the development of complementary pharmacological method-ologies has comparatively lagged. Understanding the precise pharmacological mechanisms of neuroactive compounds is critical for advancing basic neurobiology and neuropharmacology, as well as for developing more effective treatments for neurological and neuropsychiatric disorders. However, integrating modern tools for assessing neural activity in large-scale neural networks with spatially localized drug delivery remains a major challenge.

Hyperactivity of indirect pathway-projecting spiny projection neurons promotes compulsive behavior.

Compulsive behaviors are a hallmark symptom of obsessive compulsive disorder (OCD). Striatal hyperactivity has been linked to compulsive behavior generation in correlative studies in humans and causal studies in rodents. However, the contribution of the two distinct striatal output populations to the generation and treatment of compulsive behavior is unknown.

Limited information-processing capacity in vision explains number psychophysics.

Humans and other animals are able to perceive and represent a number of objects present in a scene, a core cognitive ability thought to underlie the development of mathematics. However, the perceptual mechanisms that underpin this capacity remain poorly understood. Here, we show that our visual sense of number derives from a visual system designed to efficiently encode the location of objects in scenes.

Response to Difficulty Drives Variation in IQ Test Performance.

In a large ( = 300), pre-registered experiment and data analysis model, we find that individual variation in overall performance on Raven's Progressive Matrices is substantially driven by differential strategizing in the face of difficulty. Some participants choose to spend more time on hard problems while others choose to spend less and these differences explain about 42% of the variance in overall performance. In a data analysis jointly predicting participants' reaction times and accuracy on each item, we find that the Raven's task captures at most half of participants' variation in time-controlled ability (48%) down to almost none (3%), depending on which notion of ability is assumed.

Holographic stimulation of opposing amygdala ensembles bidirectionally modulates valence-specific behavior via mutual inhibition.

The basolateral amygdala (BLA) is an evolutionarily conserved brain region, well known for valence processing. Despite this central role, the relationship between activity of BLA neuronal ensembles in response to appetitive and aversive stimuli and the subsequent expression of valence-specific behavior has remained elusive. Here, we leverage two-photon calcium imaging combined with single-cell holographic photostimulation through an endoscopic lens to demonstrate a direct causal role for opposing ensembles of BLA neurons in the control of oppositely valenced behavior in mice.

The algorithmic origins of counting.

The study of how children learn numbers has yielded one of the most productive research programs in cognitive development, spanning empirical and computational methods, as well as nativist and empiricist philosophies. This paper provides a tutorial on how to think computationally about learning models in a domain like number, where learners take finite data and go far beyond what they directly observe or perceive. To illustrate, this paper then outlines a model which acquires a counting procedure using observations of sets and words, extending the proposal of Piantadosi et al.

Deep-brain optical recording of neural dynamics during behavior.

In vivo fluorescence recording techniques have produced landmark discoveries in neuroscience, providing insight into how single cell and circuit-level computations mediate sensory processing and generate complex behaviors. While much attention has been given to recording from cortical brain regions, deep-brain fluorescence recording is more complex because it requires additional measures to gain optical access to harder to reach brain nuclei. Here we discuss detailed considerations and tradeoffs regarding deep-brain fluorescence recording techniques and provide a comprehensive guide for all major steps involved, from project planning to data analysis.

The Influence of Social Determinants on Receiving Outpatient Treatment with Monoclonal Antibodies, Disease Risk, and Effectiveness for COVID-19.

Background: Limited research has studied the influence of social determinants of health (SDoH) on the receipt, disease risk, and subsequent effectiveness of neutralizing monoclonal antibodies (nMAbs) for outpatient treatment of COVID-19.

Objective: To examine the influence of SDoH variables on receiving nMAb treatments and the risk of a poor COVID-19 outcome, as well as nMAb treatment effectiveness across SDoH subgroups.

Design: Retrospective observational study utilizing electronic health record data from four health systems.

The Plausibility of Sampling as an Algorithmic Theory of Sentence Processing.

Words that are more surprising given context take longer to process. However, no incremental parsing algorithm has been shown to directly predict this phenomenon. In this work, we focus on a class of algorithms whose runtime does naturally scale in surprisal-those that involve repeatedly sampling from the prior.

Diverse mathematical knowledge among indigenous Amazonians.

We investigate number and arithmetic learning among a Bolivian indigenous people, the Tsimane', for whom formal schooling is comparatively recent in history and variable in both extent and consistency. We first present a large-scale meta-analysis on child number development involving over 800 Tsimane' children. The results emphasize the impact of formal schooling: Children are only found to be full counters when they have attended school, suggesting the importance of cultural support for early mathematics.

Latent Diversity in Human Concepts.

Many social and legal conflicts hinge on semantic disagreements. Understanding the origins and implications of these disagreements necessitates novel methods for identifying and quantifying variation in semantic cognition between individuals. We collected conceptual similarity ratings and feature judgements from a variety of words in two domains.

Dendritic cell vaccine trials in gliomas: Untangling the lines.

Glioblastoma is a deadly brain tumor without any significantly successful treatments to date. Tumor antigen-targeted immunotherapy platforms including peptide and dendritic cell (DC) vaccines, have extended survival in hematologic malignancies. The relatively "cold" tumor immune microenvironment and heterogenous nature of glioblastoma have proven to be major limitations to translational application and efficacy of DC vaccines.