Neural responses are modulated by brain state, which varies with arousal, attention, and behavior. In mice, running and whisking desynchronize the cortex and enhance sensory responses, but the quiescent periods between bouts of exploratory behaviors have not been well-studied. We found that these periods of “quiet wakefulness” were characterized by state fluctuations on a timescale of 1–2 seconds. Small fluctuations in pupil diameter tracked these state transitions in multiple cortical areas. During dilation, the intracellular membrane potential was desynchronized, sensory responses were enhanced, and population activity was less correlated. In contrast, constriction was characterized by increased low-frequency oscillations and higher ensemble correlations. Specific subtypes of cortical interneurons were differentially activated during dilation and constriction, consistent with their participation in the observed state changes. Pupillometry has been used to index attention and mental effort in humans, but the intracellular dynamics and differences in population activity underlying this phenomenon were previously unknown.

Developments in microfabrication technology have enabled the production of neural electrode arrays with hundreds of closely-spaced recording sites, and electrodes with thousands of sites are currently under development. These probes in principle allow the simultaneous recording of very large numbers of neurons. However, use of this technology requires the development of techniques for decoding the spike times of the recorded neurons, from the raw data captured from the probes. Here, we present a set of novel tools to solve this problem, implemented in a suite of practical, user-friendly, open-source software. We validate these methods on data from the cortex, hippocampus, and thalamus of rat, mouse, macaque, and marmoset, demonstrating error rates as low as 5%.

Shared, trial-to-trial variability in neuronal populations has a strong impact on the accuracy of information processing in the brain. Estimates of the level of such noise correlations are diverse, ranging from 0.01 to 0.4, with little consensus on which factors account for these differences. Here we addressed one important factor that varied across studies, asking how anesthesia affects the population activity structure in macaque primary visual cortex. We found that under opioid anesthesia, activity was dominated by strong coordinated fluctuations on a timescale of 1–2 Hz, which were mostly absent in awake, fixating monkeys. Accounting for these global fluctuations markedly reduced correlations under anesthesia, matching those observed during wakefulness and reconciling earlier studies conducted under anesthesia and in awake animals. Our results show that internal signals, such as brain state transitions under anesthesia, can induce noise correlations, but can also be estimated and accounted for based on neuronal population activity.

Despite great efforts over several decades, our best models of primary visual cortex (V1) still predict neural responses quite poorly when probed with natural stimuli, highlighting our limited understanding of the nonlinear computations in V1. At the same time, recent advances in machine learning have shown that deep neural networks can learn highly nonlinear functions for visual information processing.Two approaches based on deep learning have recently been successfully applied to neural data: transfer learning for predicting neural activity in higher areas of the primate ventral stream and data-driven models to predict retina and V1 neural activity of mice. However, so far there exists no comparison between the two approaches and neither of them has been used to model the early primate visual system. Here, we test the ability of both approaches to predict neural responses to natural images in V1 of awake monkeys. We found that both deep learning approaches outperformed classical linearnonlinear and wavelet-based feature representations building on existing V1 encoding theories. On our dataset, transfer learning and data-driven models performed similarly, while the data-driven model employed a much simpler architecture. Thus, multi-layer CNNs set the new state of the art for predicting neural responses to natural images in primate V1. Having such good predictive in-silico models opens the door for quantitative studies of yet unknown nonlinear computations in V1 without being limited by the available experimental time.

Attention is commonly thought to improve behavioral performance by increasing response gain and suppressing shared variability in neuronal populations. However, both the focus and the strength of attention are likely to vary from one experimental trial to the next, thereby inducing response variability unknown to the experimenter. Here we study analytically how fluctuations in attentional state affect the structure of population responses in a simple model of spatial and feature attention. In our model, attention acts on the neural response exclusively by modulating each neuron's gain. Neurons are conditionally independent given the stimulus and the attentional gain, and correlated activity arises only from trial-to-trial fluctuations of the attentional state, which are unknown to the experimenter. We find that this simple model can readily explain many aspects of neural response modulation under attention, such as increased response gain, reduced individual and shared variability, increased correlations with firing rates, limited range correlations, and differential correlations. We therefore suggest that attention may act primarily by increasing response gain of individual neurons without affecting their correlation structure. The experimentally observed reduction in correlations may instead result from reduced variability of the attentional gain when a stimulus is attended. Moreover, we show that attentional gain fluctuations, even if unknown to a downstream readout, do not impair the readout accuracy despite inducing limited-range correlations, whereas fluctuations of the attended feature can in principle limit behavioral performance.

Despite great efforts over several decades, our best models of primary visual cortex (V1) still predict spiking activity quite poorly when probed with natural stimuli, highlighting our limited understanding of the nonlinear computations in V1. Recently, two approaches based on deep learning have emerged for modeling these nonlinear computations: transfer learning from artificial neural networks trained on object recognition and data-driven convolutional neural network models trained end-to-end on large populations of neurons. Here, we test the ability of both approaches to predict spiking activity in response to natural images in V1 of awake monkeys. We found that the transfer learning approach performed similarly well to the data-driven approach and both outperformed classical linear-nonlinear and wavelet-based feature representations that build on existing theories of V1. Notably, transfer learning using a pre-trained feature space required substantially less experimental time to achieve the same performance. In conclusion, multi-layer convolutional neural networks (CNNs) set the new state of the art for predicting neural responses to natural images in primate V1 and deep features learned for object recognition are better explanations for V1 computation than all previous filter bank theories. This finding strengthens the necessity of V1 models that are multiple nonlinearities away from the image domain and it supports the idea of explaining early visual cortex based on high-level functional goals.

Variability in neuronal responses to identical stimuli is frequently correlated across a population. Attention is thought to reduce these correlations by suppressing noisy inputs shared by the population. However, even with precise control of the visual stimulus, the subject’s attentional state varies across trials. While these state fluctuations are bound to induce some degree of correlated variability, it is currently unknown how strong their effect is, as previous studies generally do not dissociate changes in attentional strength from changes in attentional state variability. We designed a novel paradigm that does so and find both a pronounced effect of attentional fluctuations on correlated variability at long timescales and attention-dependent reductions in correlations at short timescales. These effects predominate in layers 2/3, as expected from a feedback signal such as attention. Thus, significant portions of correlated variability can be attributed to fluctuations in internally generated signals, like attention, rather than noise.

Favors from a sender to a receiver are known to bias decisions made by the recipient, especially when the decision relates to the sender, a feature of social exchange known as reciprocity. Using an art-viewing paradigm possessing no objectively correct answer for preferring one piece of art over another, we show that sponsorship of the experiment by a company endows the logo of the company with the capacity to bias revealed preferenceforartdisplayednexttothelogo.Merelyofferingtosponsortheexperimentsimilarlyendowedthegesturinglogoofthecompanywith the capacity to bias revealed preferences. These effects do not depend upon the size of the displayed art or the proximity of the sponsoring logo to the piece of art. We used functional magnetic resonance imaging to show that such monetary favors do not modulate a special collection of brain responses but instead modulate responses in neural networks normally activated by a wide range of preference judgments. The results raise the important possibility that monetary favors bias judgments in domains seemingly unrelated to the favor but nevertheless act in an implicit way through neural networks that underlie normal, ongoing preference judgments.