Common and distinct neural mechanisms of attention.

Despite a constant deluge of sensory stimulation, only a fraction of it is used to guide behavior. This selective processing is generally referred to as attention, and much research has focused on the neural mechanisms controlling it. Recently, research has broadened to include more ways by which different species selectively process sensory information, whether due to the sensory input itself or to different behavioral and brain states. This work has produced a complex and disjointed body of evidence across different species and forms of attention. However, it has also provided opportunities to better understand the breadth of attentional mechanisms. Here, we summarize the evidence that suggests that different forms of selective processing are supported by mechanisms both common and distinct.

The dynamics and geometry of choice in premotor cortex.

The brain represents sensory variables in the coordinated activity of neural populations, in which tuning curves of single neurons define the geometry of the population code. Whether the same coding principle holds for dynamic cognitive variables remains unknown because internal cognitive processes unfold with a unique time course on single trials observed only in the irregular spiking of heterogeneous neural populations. Here we show the existence of such a population code for the dynamics of choice formation in the primate premotor cortex. We developed an approach to simultaneously infer population dynamics and tuning functions of single neurons to the population state. Applied to spike data recorded during decision-making, our model revealed that populations of neurons encoded the same dynamic variable predicting choices, and heterogeneous firing rates resulted from the diverse tuning of single neurons to this decision variable. The inferred dynamics indicated an attractor mechanism for decision computation. Our results reveal a common geometric principle for neural encoding of sensory and dynamic cognitive variables.

A unifying perspective on neural manifolds and circuits for cognition.

Two different perspectives have informed efforts to explain the link between the brain and behaviour. One approach seeks to identify neural circuit elements that carry out specific functions, emphasizing connectivity between neurons as a substrate for neural computations. Another approach centres on neural manifolds - low-dimensional representations of behavioural signals in neural population activity - and suggests that neural computations are realized by emergent dynamics. Although manifolds reveal an interpretable structure in heterogeneous neuronal activity, finding the corresponding structure in connectivity remains a challenge. We highlight examples in which establishing the correspondence between low-dimensional activity and connectivity has been possible, unifying the neural manifold and circuit perspectives. This relationship is conspicuous in systems in which the geometry of neural responses mirrors their spatial layout in the brain, such as the fly navigational system. Furthermore, we describe evidence that, in systems in which neural responses are heterogeneous, the circuit comprises interactions between activity patterns on the manifold via low-rank connectivity. We suggest that unifying the manifold and circuit approaches is important if we are to be able to causally test theories about the neural computations that underlie behaviour.

Intrinsic timescales in the visual cortex change with selective attention and reflect spatial connectivity.

Intrinsic timescales characterize dynamics of endogenous fluctuations in neural activity. Variation of intrinsic timescales across the neocortex reflects functional specialization of cortical areas, but less is known about how intrinsic timescales change during cognitive tasks. We measured intrinsic timescales of local spiking activity within columns of area V4 in male monkeys performing spatial attention tasks. The ongoing spiking activity unfolded across at least two distinct timescales, fast and slow. The slow timescale increased when monkeys attended to the receptive fields location and correlated with reaction times. By evaluating predictions of several network models, we found that spatiotemporal correlations in V4 activity were best explained by the model in which multiple timescales arise from recurrent interactions shaped by spatially arranged connectivity, and attentional modulation of timescales results from an increase in the efficacy of recurrent interactions. Our results suggest that multiple timescales may arise from the spatial connectivity in the visual cortex and flexibly change with the cognitive state due to dynamic effective interactions between neurons.

Choice selective inhibition drives stability and competition in decision circuits.

During perceptual decision-making, the firing rates of cortical neurons reflect upcoming choices. Recent work showed that excitatory and inhibitory neurons are equally selective for choice. However, the functional consequences of inhibitory choice selectivity in decision-making circuits are unknown. We developed a circuit model of decision-making which accounts for the specificity of inputs to and outputs from inhibitory neurons. We found that selective inhibition expands the space of circuits supporting decision-making, allowing for weaker or stronger recurrent excitation when connected in a competitive or feedback motif. The specificity of inhibitory outputs sets the trade-off between speed and accuracy of decisions by either stabilizing or destabilizing the saddle-point dynamics underlying decisions in the circuit. Recurrent neural networks trained to make decisions display the same dependence on inhibitory specificity and the strength of recurrent excitation. Our results reveal two concurrent roles for selective inhibition in decision-making circuits: stabilizing strongly connected excitatory populations and maximizing competition between oppositely selective populations.

Predictive variational autoencoder for learning robust representations of time-series data.

Variational autoencoders (VAEs) have been used extensively to discover low-dimensional latent factors governing neural activity and animal behavior. However, without careful model selection, the uncovered latent factors may reflect noise in the data rather than true underlying features, rendering such representations unsuitable for scientific interpretation. Existing solutions to this problem involve introducing additional measured variables or data augmentations specific to a particular data type. We propose a VAE architecture that predicts the next point in time and show that it mitigates the learning of spurious features. In addition, we introduce a model selection metric based on smoothness over time in the latent space. We show that together these two constraints on VAEs to be smooth over time produce robust latent representations and faithfully recover latent factors on synthetic datasets.

Recent Advances at the Interface of Neuroscience and Artificial Neural Networks.

Biological neural networks adapt and learn in diverse behavioral contexts. Artificial neural networks (ANNs) have exploited biological properties to solve complex problems. However, despite their effectiveness for specific tasks, ANNs are yet to realize the flexibility and adaptability of biological cognition. This review highlights recent advances in computational and experimental research to advance our understanding of biological and artificial intelligence. In particular, we discuss critical mechanisms from the cellular, systems, and cognitive neuroscience fields that have contributed to refining the architecture and training algorithms of ANNs. Additionally, we discuss how recent work used ANNs to understand complex neuronal correlates of cognition and to process high throughput behavioral data.

Cortical state dynamics and selective attention define the spatial pattern of correlated variability in neocortex.

Correlated activity fluctuations in the neocortex influence sensory responses and behavior. Neural correlations reflect anatomical connectivity but also change dynamically with cognitive states such as attention. Yet, the network mechanisms defining the population structure of correlations remain unknown. We measured correlations within columns in the visual cortex. We show that the magnitude of correlations, their attentional modulation, and dependence on lateral distance are explained by columnar On-Off dynamics, which are synchronous activity fluctuations reflecting cortical state. We developed a network model in which the On-Off dynamics propagate across nearby columns generating spatial correlations with the extent controlled by attentional inputs. This mechanism, unlike previous proposals, predicts spatially non-uniform changes in correlations during attention. We confirm this prediction in our columnar recordings by showing that in superficial layers the largest changes in correlations occur at intermediate lateral distances. Our results reveal how spatially structured patterns of correlated variability emerge through interactions of cortical state dynamics, anatomical connectivity, and attention.

A flexible Bayesian framework for unbiased estimation of timescales.

Timescales characterize the pace of change for many dynamic processes in nature. Timescales are usually estimated by fitting the exponential decay of data autocorrelation in the time or frequency domain. Here we show that this standard procedure often fails to recover the correct timescales due to a statistical bias arising from the finite sample size. We develop an alternative approach which estimates timescales by fitting the sample autocorrelation or power spectrum with a generative model based on a mixture of Ornstein-Uhlenbeck (OU) processes using adaptive approximate Bayesian computations (aABC). Our method accounts for finite sample size and noise in data and returns a posterior distribution of timescales that quantifies the estimation uncertainty and can be used for model selection. We demonstrate the accuracy of our method on synthetic data and illustrate its application to recordings from primate cortex. We provide a customizable Python package implementing our framework with different generative models suitable for diverse applications.

The diversity and specificity of functional connectivity across spatial and temporal scales.

Macroscopic neuroimaging modalities in humans have revealed the organization of brain-wide activity into distributed functional networks that re-organize according to behavioral demands. However, the inherent coarse-graining of macroscopic measurements conceals the diversity and specificity in responses and connectivity of many individual neurons contained in each local region. New invasive approaches in animals enable recording and manipulating neural activity at meso- and microscale resolution, with cell-type specificity and temporal precision down to milliseconds. Determining how brain-wide activity patterns emerge from interactions across spatial and temporal scales will allow us to identify the key circuit mechanisms contributing to global brain states and how the dynamic activity of these states enables adaptive behavior.

Learning non-stationary Langevin dynamics from stochastic observations of latent trajectories.

Many complex systems operating far from the equilibrium exhibit stochastic dynamics that can be described by a Langevin equation. Inferring Langevin equations from data can reveal how transient dynamics of such systems give rise to their function. However, dynamics are often inaccessible directly and can be only gleaned through a stochastic observation process, which makes the inference challenging. Here we present a non-parametric framework for inferring the Langevin equation, which explicitly models the stochastic observation process and non-stationary latent dynamics. The framework accounts for the non-equilibrium initial and final states of the observed system and for the possibility that the system's dynamics define the duration of observations. Omitting any of these non-stationary components results in incorrect inference, in which erroneous features arise in the dynamics due to non-stationary data distribution. We illustrate the framework using models of neural dynamics underlying decision making in the brain.

Top-down coordination of local cortical state during selective attention.

Spontaneous fluctuations in cortical excitability influence sensory processing and behavior. These fluctuations, long thought to reflect global changes in cortical state, were recently found to be modulated locally within a retinotopic map during spatially selective attention. We report that periods of vigorous (On) and faint (Off) spiking activity, the signature of cortical state fluctuations, are coordinated across brain areas with retinotopic precision. Top-down attention enhanced interareal local state coordination, traversing along the reverse cortical hierarchy. The extent of local state coordination between areas was predictive of behavioral performance. Our results show that cortical state dynamics are shared across brain regions, modulated by cognitive demands and relevant for behavior.

Moving beyond generalization to accurate interpretation of flexible models.

Machine learning optimizes flexible models to predict data. In scientific applications, there is a rising interest in interpreting these flexible models to derive hypotheses from data. However, it is unknown whether good data prediction guarantees accurate interpretation of flexible models. Here we test this connection using a flexible, yet intrinsically interpretable framework for modelling neural dynamics. We find that many models discovered during optimization predict data equally well, yet they fail to match the correct hypothesis. We develop an alternative approach that identifies models with correct interpretation by comparing model features across data samples to separate true features from noise. We illustrate our findings using recordings of spiking activity from the visual cortex of behaving monkeys. Our results reveal that good predictions cannot substitute for accurate interpretation of flexible models and offer a principled approach to identify models with correct interpretation.

New perspectives on dimensionality and variability from large-scale cortical dynamics.

The neocortex is a multi-scale network, with intricate local circuitry interwoven into a global mesh of long-range connections. Neural activity propagates within this network on a wide range of temporal and spatial scales. At the micro scale, neurophysiological recordings reveal coordinated dynamics in local neural populations, which support behaviorally relevant computations. At the macro scale, neuroimaging modalities measure global activity fluctuations organized into spatiotemporal patterns across the entire brain. Here we review recent advances linking the local and global scales of cortical dynamics and their relationship to behavior. We argue that diverse experimental observations on the dimensionality and variability of neural activity can be reconciled by considering how activity propagates in space and time on multiple spatial scales.

Selective modulation of cortical state during spatial attention.

Neocortical activity is permeated with endogenously generated fluctuations, but how these dynamics affect goal-directed behavior remains a mystery. We found that ensemble neural activity in primate visual cortex spontaneously fluctuated between phases of vigorous (On) and faint (Off) spiking synchronously across cortical layers. These On-Off dynamics, reflecting global changes in cortical state, were also modulated at a local scale during selective attention. Moreover, the momentary phase of local ensemble activity predicted behavioral performance. Our results show that cortical state is controlled locally within a cortical map according to cognitive demands and reveal the impact of these local changes in cortical state on goal-directed behavior.

Choice-correlated activity fluctuations underlie learning of neuronal category representation.

The ability to categorize stimuli into discrete behaviourally relevant groups is an essential cognitive function. To elucidate the neural mechanisms underlying categorization, we constructed a cortical circuit model that is capable of learning a motion categorization task through reward-dependent plasticity. Here we show that stable category representations develop in neurons intermediate to sensory and decision layers if they exhibit choice-correlated activity fluctuations (choice probability). In the model, choice probability and task-specific interneuronal correlations emerge from plasticity of top-down projections from decision neurons. Specific model predictions are confirmed by analysis of single-neuron activity from the monkey parietal cortex, which reveals a mixture of directional and categorical tuning, and a positive correlation between category selectivity and choice probability. Beyond demonstrating a circuit mechanism for categorization, the present work suggests a key role of plastic top-down feedback in simultaneously shaping both neural tuning and correlated neural variability.

Impact of Hyperpolarization-activated, Cyclic Nucleotide-gated Cation Channel Type 2 for the Xenon-mediated Anesthetic Effect: Evidence from In Vitro and In Vivo Experiments.

BACKGROUND: The thalamus is thought to be crucially involved in the anesthetic state. Here, we investigated the effect of the inhaled anesthetic xenon on stimulus-evoked thalamocortical network activity and on excitability of thalamocortical neurons. Because hyperpolarization-activated, cyclic nucleotide-gated cation (HCN) channels are key regulators of neuronal excitability in the thalamus, the effect of xenon on HCN channels was examined. METHODS: The effects of xenon on thalamocortical network activity were investigated in acutely prepared brain slices from adult wild-type and HCN2 knockout mice by means of voltage-sensitive dye imaging. The influence of xenon on single-cell excitability in brain slices was investigated using the whole-cell patch-clamp technique. Effects of xenon on HCN channels were verified in human embryonic kidney cells expressing HCN2 channels. RESULTS: Xenon concentration-dependently diminished thalamocortical signal propagation. In neurons, xenon reduced HCN channel-mediated Ih current amplitude by 33.4 ± 12.2% (at -133 mV; n = 7; P = 0.041) and caused a left-shift in the voltage of half-maximum activation (V1/2) from -98.8 ± 1.6 to -108.0 ± 4.2 mV (n = 8; P = 0.035). Similar effects were seen in human embryonic kidney cells. The impairment of HCN channel function was negligible when intracellular cyclic adenosine monophosphate level was increased. Using HCN2 mice, we could demonstrate that xenon did neither attenuate in vitro thalamocortical signal propagation nor did it show sedating effects in vivo. CONCLUSIONS: Here, we clearly showed that xenon impairs HCN2 channel function, and this impairment is dependent on intracellular cyclic adenosine monophosphate levels. We provide evidence that this effect reduces thalamocortical signal propagation and probably contributes to the hypnotic properties of xenon.

Same or different? A neural circuit mechanism of similarity-based pattern match decision making.

The ability to judge whether sensory stimuli match an internally represented pattern is central to many brain functions. To elucidate the underlying mechanism, we developed a neural circuit model for match/nonmatch decision making. At the core of this model is a "comparison circuit" consisting of two distinct neural populations: match enhancement cells show higher firing response for a match than a nonmatch to the target pattern, and match suppression cells exhibit the opposite trend. We propose that these two neural pools emerge from inhibition-dominated recurrent dynamics and heterogeneous top-down excitation from a working memory circuit. A downstream system learns, through plastic synapses, to extract the necessary information to make match/nonmatch decisions. The model accounts for key physiological observations from behaving monkeys in delayed match-to-sample experiments, including tasks that require more than simple feature match (e.g., when BB in ABBA sequence must be ignored). A testable prediction is that magnitudes of match enhancement and suppression neural signals are parametrically tuned to the similarity between compared patterns. Furthermore, the same neural signals from the comparison circuit can be used differently in the decision process for different stimulus statistics or tasks; reward-dependent synaptic plasticity enables decision neurons to flexibly adjust the readout scheme to task demands, whereby the most informative neural signals have the highest impact on the decision.