Flexibly responding to sensory cues is fundamental to animal behavior. However, growing evidence suggests that the relevant neural circuits have been incompletely resolved. We trained mice to apply an abstract rule that maps identical visual stimuli to opposing actions across contexts and investigated the role of the midbrain reticular formation (MRF) in this process. Large-scale recordings revealed that neurons in the MRF, along with several canonical decision-making areas, maintained persistent representations of task context in pre-stimulus activity. These representations predicted divergent population dynamics, putatively routing stimuli toward context-appropriate actions. The MRF was the only recorded region containing neuronal populations that both predicted lapses in contextual control pre-stimulus and exhibited contextually modulated premotor responses. The MRF also showed task-specific sensory plasticity. Context-coding neurons were aligned with cortical inputs, suggesting a spatial organization. These findings support the hypothesis that the MRF is a key node for setting and implementing abstract contextual states within the distributed circuitry for flexible perceptual decisions.

The hippocampal formation is a highly curved and topographically complex forebrain structure. This complex geometry presents persistent challenges for analyzing subregional, laminar, and connectivity patterns. Here, we present a computational workflow that generates curvilinear-coordinate flatmaps from Common Coordinate Framework (CCF) registered hippocampal and retrohippocampal regions by solving the Laplacian equation to derive geodesic streamlines. This transformation unfolds the hippocampus into a planar slab, bounded by the meningeal and ventricular surfaces, with the depth defined along the radial axis. We apply this transform to image volumes, single neuron reconstructions, and point data, including spatial transcriptomic and rabies tracing datasets, revealing topographic variations in the dorsoventral and radial axes that are obscured in the CCF coordinate space. As proof of principle, we use flatmaps to show connectivity loss in a mouse model of Alzheimer's disease and track postnatal development of microglial distribution in the hippocampus. This work provides an efficient and accessible resource for visualizing hippocampal organization across development and disease, offering new opportunities to interrogate the structure and function of this important brain region.

Leveraging large-scale neuroscience datasets requires new collaborative approaches. The International Brain Laboratory (IBL) is a distributed, open-science experiment facing these challenges. To succeed, IBL developed methods for shared decision-making, division of labor, authorship/credit assignment, career support, standardization, and robust data analysis. We share these lessons learned to benefit other collaborative scientific efforts.

Patterns of brain activity moving in waves occur across brain regions and species, yet their spatial organization, anatomical basis, and brain-wide distribution remain unclear. Using cortex-wide imaging and electrophysiology in awake mice, we revealed a prominent wave motif across spatial scales. Waves frequently formed rotational patterns centered on somatosensory cortex and sweeping across somatotopic maps. Axonal architecture within sensory cortex exhibited a matching circular arrangement. Rotating waves were mirrored between hemispheres and between sensory and motor cortex and were coordinated with subcortical spiking. Bilaterally cutting the circular circuitry diminished rotating waves. Rotating waves were modulated across behavioral states, evoked by sensory inputs, and recruited during correct visuomotor performance. These results establish that rotating waves are sculpted by axonal architecture across diverse brain systems and behavioral contexts.

A key challenge in neuroscience is understanding how neurons in hundreds of interconnected brain regions integrate sensory inputs with previous expectations to initiate movements and make decisions(1). It is difficult to meet this challenge if different laboratories apply different analyses to different recordings in different regions during different behaviours. Here we report a comprehensive set of recordings from 621,733 neurons recorded with 699 Neuropixels probes across 139 mice in 12 laboratories. The data were obtained from mice performing a decision-making task with sensory, motor and cognitive components. The probes covered 279 brain areas in the left forebrain and midbrain and the right hindbrain and cerebellum. We provide an initial appraisal of this brain-wide map and assess how neural activity encodes key task variables. Representations of visual stimuli transiently appeared in classical visual areas after stimulus onset and then spread to ramp-like activity in a collection of midbrain and hindbrain regions that also encoded choices. Neural responses correlated with impending motor action almost everywhere in the brain. Responses to reward delivery and consumption were also widespread. This publicly available dataset represents a resource for understanding how computations distributed across and within brain areas drive behaviour.

Understanding brain function relies on the collective work of many labs generating reproducible results. However, reproducibility has not been systematically assessed within the context of electrophysiological recordings during cognitive behaviors. To address this, we formed a multi-lab collaboration using a shared, open-source behavioral task and experimental apparatus. Experimenters in 10 laboratories repeatedly targeted Neuropixels probes to the same location (spanning secondary visual areas, hippocampus, and thalamus) in mice making decisions; this generated a total of 121 experimental replicates, a unique dataset for evaluating reproducibility of electrophysiology experiments. Despite standardizing both behavioral and electrophysiological procedures, some experimental outcomes were highly variable. A closer analysis uncovered that variability in electrode targeting hindered reproducibility, as did the limited statistical power of some routinely used electrophysiological analyses, such as single-neuron tests of modulation by individual task parameters. Reproducibility was enhanced by histological and electrophysiological quality-control criteria. Our observations suggest that data from systems neuroscience is vulnerable to a lack of reproducibility, but that across-lab standardization, including metrics we propose, can serve to mitigate this.

The neural representations of prior information about the state of the world are poorly understood1. Here, to investigate them, we examined brain-wide Neuropixels recordings and widefield calcium imaging collected by the International Brain Laboratory. Mice were trained to indicate the location of a visual grating stimulus, which appeared on the left or right with a prior probability alternating between 0.2 and 0.8 in blocks of variable length. We found that mice estimate this prior probability and thereby improve their decision accuracy. Furthermore, we report that this subjective prior is encoded in at least 20% to 30% of brain regions that, notably, span all levels of processing, from early sensory areas (the lateral geniculate nucleus and primary visual cortex) to motor regions (secondary and primary motor cortex and gigantocellular reticular nucleus) and high-level cortical regions (the dorsal anterior cingulate area and ventrolateral orbitofrontal cortex). This widespread representation of the prior is consistent with a neural model of Bayesian inference involving loops between areas, as opposed to a model in which the prior is incorporated only in decision-making areas. This study offers a brain-wide perspective on prior encoding at cellular resolution, underscoring the importance of using large-scale recordings on a single standardized task.

To understand the neural basis of behavior, it is essential to sensitively and accurately measure neural activity at single-neuron and single-spike resolution. Extracellular electrophysiology delivers this, but it has biases in the neurons it detects and it imperfectly resolves their action potentials. To minimize these limitations, we developed a silicon probe with much smaller and denser recording sites than previous designs, called Neuropixels Ultra (NP Ultra). Using NP Ultra, neuronal yield in mouse visual cortex recordings increased by more than 2-fold. With ultra-high spatial resolution, we discovered that a feature of extracellular waveforms, the spatial extent or “footprint,” distinguished axonal from somatic recordings. In addition, three genetically identified cortical cell types could be discriminated from one another with ∼80% accuracy and from other neurons with ∼85% accuracy. NP Ultra improves yield, detection of subcellular compartments, and cell type identification to enable a more powerful dissection of neural circuit activity during behavior.

To understand the neural basis of behavior, it is essential to sensitively and accurately measure neural activity at single neuron and single spike resolution. Extracellular electrophysiology delivers this, but it has biases in the neurons it detects and it imperfectly resolves their action potentials. To minimize these limitations, we developed a silicon probe with much smaller and denser recording sites than previous designs, called Neuropixels Ultra (NP Ultra). This device samples neuronal activity at ultra-high spatial density (~10 times higher than previous probes) with low noise levels, while trading off recording span. NP Ultra is effectively an implantable voltage-sensing camera that captures a planar image of a neuron's electrical field. We use a spike sorting algorithm optimized for these probes to demonstrate that the yield of visually-responsive neurons in recordings from mouse visual cortex improves up to ~3-fold. We show that NP Ultra can record from small neuronal structures including axons and dendrites. Recordings across multiple brain regions and four species revealed a subset of extracellular action potentials with unexpectedly small spatial spread and axon-like features. We share a large-scale dataset of these brain-wide recordings in mice as a resource for studies of neuronal biophysics. Finally, using ground-truth identification of three major inhibitory cortical cell types, we found that these cell types were discriminable with approximately 75% success, a significant improvement over lower-resolution recordings. NP Ultra improves spike sorting performance, detection of subcellular compartments, and cell type classification to enable more powerful dissection of neural circuit activity during behavior.

Methodological advances in neuroscience have enabled the collection of massive datasets which demand innovative approaches for scientific communication. Existing platforms for data storage lack intuitive tools for data exploration, limiting our ability to interact effectively with these brain-wide datasets. We introduce two public websites: Data and Atlas developed for the International Brain Laboratory which provide access to millions of behavioral trials and hundreds of thousands of individual neurons. These interfaces allow users to discover both the raw and processed brain-wide data released by the IBL at the scale of the whole brain, individual sessions, trials, and neurons. By hosting these data interfaces as websites they are available cross-platform with no installation. By releasing each site's code as a modular open-source framework, other researchers can easily develop their own web interfaces and explore their own data. As neuroscience datasets continue to expand, customizable web interfaces offer a glimpse into a future of streamlined data exploration and act as blueprints for future tools.

The neural representations of prior information about the state of the world are poorly understood. To investigate this issue, we examined brain-wide Neuropixels recordings and widefield calcium imaging collected by the International Brain Laboratory. Mice were trained to indicate the location of a visual grating stimulus, which appeared on the left or right with prior probability alternating between 0.2 and 0.8 in blocks of variable length. We found that mice estimate this prior probability and thereby improve their decision accuracy. Furthermore, we report that this subjective prior is encoded in at least 20% to 30% of brain regions which, remarkably, span all levels of processing, from early sensory areas (LGd, VISp) to motor regions (MOs, MOp, GRN) and high level cortical regions (ACCd, ORBvl). This widespread representation of the prior is consistent with a neural model of Bayesian inference involving loops between areas, as opposed to a model in which the prior is incorporated only in decision making areas. This study offers the first brain-wide perspective on prior encoding at cellular resolution, underscoring the importance of using large scale recordings on a single standardized task.

Targeting deep brain structures during electrophysiology and injections requires intensive training and expertise. Even with experience, researchers often can’t be certain that a probe is placed precisely in a target location and this complexity scales with the number of simultaneous probes used in an experiment. Here, we present Pinpoint , open-source software that allows for interactive exploration of stereotaxic insertion plans. Once an insertion plan is created, Pinpoint allows users to save these online and share them with collaborators. 3D modeling tools allow users to explore their insertions alongside rig and implant hardware and ensure plans are physically possible. Probes in Pinpoint can be linked to electronic micro-manipulators allowing real-time visualization of current brain region targets alongside neural data. In addition, Pinpoint can control manipulators to automate and parallelize the insertion process. Compared to previously available software, Pinpoint’s easy access through web browsers, extensive features, and real-time experiment integration enable more efficient and reproducible recordings.

Attention allows us to focus sensory processing on behaviorally relevant aspects of the visual world. One potential mechanism of attention is a change in the gain of sensory responses. However, changing gain at early stages could have multiple downstream consequences for visual processing. Which, if any, of these effects can account for the benefits of attention for detection and discrimination? Using a model of primate visual cortex we document how a Gaussian-shaped gain modulation results in changes to spatial tuning properties. Forcing the model to use only these changes failed to produce any benefit in task performance. Instead, we found that gain alone was both necessary and sufficient to explain category detection and discrimination during attention. Our results show how gain can give rise to changes in receptive fields which are not necessary for enhancing task performance.

Traveling waves of activity are a prevalent phenomenon within neural networks of diverse brain regions and species[1][1]–[4][2], and have been implicated in myriad brain functions including sensory perception[5][3]–[8][4], memory[9][5], spatial navigation[10][6]–[12][7] and motor control[13][8],[14][9]. However, the anatomical basis for these waves, and whether they are locally confined versus distributed across the brain, remains unclear. Here we use cortex-wide imaging and large-scale electrophysiology in awake mice to reveal the organization of traveling waves across spatial scales. Traveling waves formed spiral patterns predominantly centered on somatosensory cortex. Strikingly, the local axonal architecture of neurons in sensory cortex exhibited a matching circular arrangement. At the cortex-wide scale, these spiral waves were mirrored between hemispheres and between sensory and motor cortex, reflecting topographic long-range axons. Finally, at the brain-wide scale, cortical spiral waves were coordinated with subcortical spiking patterns in the thalamus, striatum and midbrain. These results establish that traveling waves are structured by axonal pathways and globally impact neural activity across diverse brain systems. ### Competing Interest Statement The authors have declared no competing interest. [1]: #ref-1 [2]: #ref-4 [3]: #ref-5 [4]: #ref-8 [5]: #ref-9 [6]: #ref-10 [7]: #ref-12 [8]: #ref-13 [9]: #ref-14

A key challenge in neuroscience is understanding how neurons in hundreds of interconnected brain regions integrate sensory inputs with prior expectations to initiate movements. It has proven difficult to meet this challenge when different laboratories apply different analyses to different recordings in different regions during different behaviours. Here, we report a comprehensive set of recordings from 115 mice in 11 labs performing a decision-making task with sensory, motor, and cognitive components, obtained with 547 Neuropixels probe insertions covering 267 brain areas in the left forebrain and midbrain and the right hindbrain and cerebellum. We provide an initial appraisal of this brain-wide map, assessing how neural activity encodes key task variables. Representations of visual stimuli appeared transiently in classical visual areas after stimulus onset and then spread to ramp-like activity in a collection of mid- and hindbrain regions that also encoded choices. Neural responses correlated with motor action almost everywhere in the brain. Responses to reward delivery and consumption versus reward omission were also widespread. Representations of objective prior expectations were weaker, found in sparse sets of neurons from restricted regions. This publicly available dataset represents an unprecedented resource for understanding how computations distributed across and within brain areas drive behaviour.

Human observers use cues to guide visual attention to the most behaviorally relevant parts of the visual world. Cues are often separated into two forms: those that rely on spatial location and those that use features, such as motion or color. These forms of cueing are known to rely on different populations of neurons. Despite these differences in neural implementation, attention may rely on shared computational principles, enhancing and selecting sensory representations in a similar manner for all types of cues. Here we examine whether evidence for shared computational mechanisms can be obtained from how attentional cues enhance performance in estimation tasks. In our tasks, observers were cued either by spatial location or feature to two of four dot patches. They then estimated the color or motion direction of one of the cued patches, or averaged them. In all cases we found that cueing improved performance. We decomposed the effects of the cues on behavior into model parameters that separated sensitivity enhancement from sensory selection and found that both were important to explain improved performance. We found that a model which shared parameters across forms of cueing was favored by our analysis, suggesting that observers have equal sensitivity and likelihood of making selection errors whether cued by location or feature. Our perceptual data support theories in which a shared computational mechanism is re-used by all forms of attention. Significance Statement Cues about important features or locations in visual space are similar from the perspective of visual cortex, both allow relevant sensory representations to be enhanced while irrelevant ones can be ignored. Here we studied these attentional cues in an estimation task designed to separate different computational mechanisms of attention. Despite cueing observers in three different ways, to spatial locations, colors, or motion directions, we found that all cues led to similar perceptual improvements. Our results provide behavioral evidence supporting the idea that all forms of attention can be reconciled as a single repeated computational motif, re-implemented by the brain in different neural architectures for many different visual features.

Behavioral tasks which engage visual attention ask observers to select some sensory stimuli while ignoring others. Such tasks can be split according to how observers select visual space: either by spatial location or according to stimulus features such as color or motion direction. Most task designs elicit one or the other form of selection--but how do these compare to each other? Here we designed an estimation task to measure perceptual sensitivity to visual stimuli selected by spatial location, feature dimensions, or both. Observers fixated while four patches of colored random dot motion were shown, with each patch moving in a different direction. Two of the patches overlapped on each side of fixation and within each overlapping pair one patch was colored yellow and one blue. Observers were asked to estimate the direction of the dots within a single patch, defined by color (yellow/blue) and location (left/right), using a rotating wheel. This meant that in advance observers could be cued about which side the relevant patch would be on and then post-cued about the color, or vice versa. In control conditions observers were told the exact patch to select in advance, or given no information. We also repeated the task asking observers to estimate the color of the dot patches while cueing by direction (i.e. the four patches had random colors, and moved in one of two directions on each side). A mixture of Von Mises model showed that as expected observers (n=5, >2000 trials each) were more accurate when cued in advance. But we also found that observers were equally capable of using cues about features or location prior to stimulus presentation. Our results suggest that although selection may be implemented in many different ways these all result in a common perceptual improvement.

Attention can both enhance and suppress cortical sensory representations. However, changing sensory representations can also be detrimental to behavior. Behavioral consequences can be avoided by flexibly changing sensory readout, while leaving the representations unchanged. Here, we asked human observers to attend to and report about either one of two features which control the visibility of motion while making concurrent measurements of cortical activity with BOLD imaging (fMRI). We extend a well-established linking model to account for the relationship between these measurements and find that changes in sensory representation during directed attention are insufficient to explain perceptual reports. Adding a flexible downstream readout is necessary to best explain our data. Such a model implies that observers should be able to recover information about ignored features, a prediction which we confirm behaviorally. Thus, flexible readout is a critical component of the cortical implementation of human adaptive behavior.

Despite the central use of motion visibility to reveal the neural basis of perception, perceptual decision making, and sensory inference there exists no comprehensive quantitative framework establishing how motion visibility parameters modulate human cortical response. Random-dot motion stimuli can be made less visible by reducing image contrast or motion coherence, or by shortening the stimulus duration. Because each of these manipulations modulates the strength of sensory neural responses they have all been extensively used to reveal cognitive and other non-sensory phenomenon such as the influence of priors, attention, and choice-history biases. However, each of these manipulations is thought to influence response in different ways across different cortical regions and a comprehensive study is required to interpret this literature. Here, human participants observed random-dot stimuli varying across a large range of contrast, coherence, and stimulus durations as we measured blood-oxygen-level dependent responses. We developed a framework for modeling these responses which quantifies their functional form and sensitivity across areas. Our framework demonstrates the sensitivity of all visual areas to each parameter, with early visual areas V1-V4 showing more parametric sensitivity to changes in contrast and V3A and MT to coherence. Our results suggest that while motion contrast, coherence, and duration share cortical representation, they are encoded with distinct functional forms and sensitivity. Thus, our quantitative framework serves as a reference for interpretation of the vast perceptual literature manipulating these parameters and shows that different manipulations of visibility will have different effects across human visual cortex and need to be interpreted accordingly.