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How the brain supports speaking and listening during conversation of its natural form remains poorly understood. Here, by combining intracranial EEG recordings with Natural Language Processing, the authors show broadly distributed frontotemporal neural signals that encode context-dependent linguistic information during both speaking and listening..

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Current intracortical brain-computer interfaces are subject to recording interface instabilities that degrade decoding performance. Here, the authors present a platform for Nonlinear Manifold Alignment with Dynamics (NoMAD), which stabilizes decoding using models of dynamics for at least 3 months.

DREDge is a software tool for motion correction of high-density electrophysiology recordings. It can handle action potential or local field potential data and is demonstrated on a variety of acute or chronic recordings from humans, nonhuman primates and mice.

Neuropixels recordings from the language-dominant prefrontal cortex reveal a structured organization of planned words, an encoding cascade of phonetic representations by prefrontal neurons in humans and a cellular process that could support the production of speech.

Analyses of whole-genome and RNA sequencing data from 2,733 African American, Puerto Rican and Mexican American individuals reveal ancestry-specific patterns in the genetic architecture of whole-blood gene expression.

This Comment calls on scientists to acknowledge how insufficient communication and limited engagement beyond academia have deepened the divide between science and the public. Restoring trust requires a paradigm shift in which scientists accept that the responsibility to champion science lies with us. We propose a new model in which public communication and advocacy are considered as essential to our mission as rigor and reproducibility — critical not only for safeguarding science, but also for ensuring that its benefits reach all segments of the societies we serve.

Here the authors conduct a multi-ancestry meta-analysis of telomere length, used diverse approaches to identify genes underlying association signals, and experimentally validated POP5 and KBTBD6 as regulators of telomere length in human cells.

Wireless tracking of neuronal activity in social groups of mice identifies neurons in the anterior cingulate that hold representations of an animal’s social rank and can influence the competitive effort that the animal exerts.

Electrodes available for deep brain recording and stimulation have a number of limitations. Here the authors describe a thin-film depth electrode that may offer improved spatial and temporal resolution for recording brain activity.

A study shows that clonal haematopoiesis of indeterminate potential is associated with an increased risk of chronic liver disease specifically through the promotion of liver inflammation and injury.

The neural mechanisms underpinning ketamine’s dissociative and antidepressant effects remain poorly understood. Here, the authors analyzed ketamine-induced brain dynamics with intracranial recordings in humans and found that ketamine engages different brain areas in distinct frequency-dependent patterns that may relate to its dissociative and antidepressant effects.

Neural mechanisms underpinning theta burst stimulation (TBS) and its implications for neuropsychiatric disorders are not fully understood. Here authors show theta burst stimulation delivered by intracranial electrodes results in measurable responses that change over time, suggestive of neuroplasticity. These responses can be predicted by baseline biophysical parameters such as functional connectivity.

By tracking the activity of individual neurons using microarrays and Neuropixels probes, a study examines the representation of linguistic meaning, at the single-cell level, during natural speech processing in humans.

Analyses of layer 5 cortical pyramidal neurons in 10 mammalian species show that human neurons are distinct in that they do not follow the expected allometric relationship between neuron size and membrane conductance.

Recordings of cells in the human dorsomedial prefrontal cortex identify a population of neurons that encode information about others’ beliefs and distinguish them from self-belief-related representations, providing insight into cellular-level processing underlying human theory of mind.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

Functional imaging, single-cell recording and targeted surgical lesions were used in human patients undergoing cingulotomy to show that the dorsal anterior cingulate cortex provides a continuously updated prediction of expected cognitive demand.

STAARpipeline is a comprehensive framework for flexible and scalable rare-variant association analysis using whole-genome sequencing data and annotation information.

Brain–machine interfaces are being investigated for recovery of motor function after paralysis. Shanechi et al.present a neural prosthesis that decodes premotor neuronal activity in an alert monkey to activate spinal neurons and muscles that produce target-directed movements in a sedated monkey or avatar.

The authors discover neurons in the human prefrontal cortex that encode subjective decisions and that may underlie the process by which opinions are formed. They also find how disruption of these neurons selectively interferes with the decision-making process.

Lee et al. show that in male Shank3-mutant mice, mPFC neurons are impaired in encoding of social agency. Shank3 reexpression in mPFC restored this ability in real time, and this was accompanied by rescue of normal social behavior.

Insight into the mechanism by which deep brain stimulation exerts its therapeutic effects comes from recording in motor cortical regions of neurosurgical subjects undergoing subthalamic nucleus deep brain stimulation.

Long-term cultures of human brain organoids display a high degree of cellular diversity, mature spontaneous neuronal networks and are sensitive to light.

There is currently no disease-modifying treatment for Parkinson’s disease, a common neurodegenerative disorder. Here, the authors use genetic variation associated with gene and protein expression to find putative drug targets for Parkinson’s disease using Mendelian randomization of the druggable genome.

Functional morphemes allow us to express details about objects, events, and their relationships. Here, authors show that inhibiting a small cortical area within left posterior superior temporal lobe selectively impairs the ability to produce functional morphemes but does not impair other linguistic abilities.

Neuropixels probes were used to simultaneously record from more than 200 cortical neurons in human participants during neurosurgical procedures. The approach could reveal insights underlying human cognition and pathology.

Single-unit ensemble activity recorded in unilateral human precentral gyrus reveals a wide range of gesture-related signals across both hands, providing an intuitive and diverse set of potential command signals for intracortical BCI use.

Brain-machine interfaces (BMIs) have typically focused on performing single-targeted movements. Here the authors report the presence of two subpopulations of neurons in the monkey premotor cortex that allow two planned targets to be simultaneously held in working memory without degradation. They use this finding to develop a BMI that concurrently decodes a full motor sequence in advance of movement and then accurately executes it.

MetaSTAAR enables functionally informed rare variant association analysis in biobank-scale cohorts using an efficient, sparse matrix approach for summary statistic storage.

Knowledge of genomic features specific to humans may be important for understanding disease. Here the authors demonstrate a potential role for these human-lineage-specific sequences in brain development and neurological disease.

Launched in 2013, the BRAIN Initiative (BRAIN) in the United States aimed to unlock the mysteries of the brain and develop new treatments for neurological and neuropsychiatric disorders. The success of this program is evidenced by the accelerated discoveries and development of interventions that are happening in real time. However, a recent 40% cut in funding for BRAIN threatens this once-in-a-generation opportunity to solve fundamental mysteries of the brain and achieve treatment breakthroughs that we once thought impossible.

Regulation of gene expression and splicing are thought to be tissue-specific. Here, the authors obtain genomic and transcriptomic data from putamen and substantia nigra of 117 neurologically healthy human brains and find that splicing eQTLs are enriched for neuron-specific regulatory information.

How does the intricate balance of gene regulation and expression within individual neurons relate to electrophysiological oscillations and, ultimately, cognition? In a new study, Berto and colleagues take an important step toward addressing this question by correlating oscillatory biomarkers of successful memory encoding with gene expression on a within-participant basis.

This Protocol documents the extensive preparation required to adopt Neuropixels probes for use in patients for recording spiking activity from up to hundreds of cortical neurons and associating it with local field potentials.