Behavior- and Modality-General Representation of Confidence in Orbitofrontal Cortex.

Every decision we make is accompanied by a sense of confidence about its likely outcome. This sense informs subsequent behavior, such as investing more-whether time, effort, or money-when reward is more certain. A neural representation of confidence should originate from a statistical computation and predict confidence-guided behavior. An additional requirement for confidence representations to support metacognition is abstraction: they should emerge irrespective of the source of information and inform multiple confidence-guided behaviors. It is unknown whether neural confidence signals meet these criteria. Here, we show that single orbitofrontal cortex neurons in rats encode statistical decision confidence irrespective of the sensory modality, olfactory or auditory, used to make a choice. The activity of these neurons also predicts two confidence-guided behaviors: trial-by-trial time investment and cross-trial choice strategy updating. Orbitofrontal cortex thus represents decision confidence consistent with a metacognitive process that is useful for mediating confidence-guided economic decisions.

Frontal cortex neuron types categorically encode single decision variables.

Individual neurons in many cortical regions have been found to encode specific, identifiable features of the environment or body that pertain to the function of the region1-3. However, in frontal cortex, which is involved in cognition, neural responses display baffling complexity, carrying seemingly disordered mixtures of sensory, motor and other task-related variables4-13. This complexity has led to the suggestion that representations in individual frontal neurons are randomly mixed and can only be understood at the neural population level14,15. Here we show that neural activity in rat orbitofrontal cortex (OFC) is instead highly structured: single neuron activity co-varies with individual variables in computational models that explain choice behaviour. To characterize neural responses across a large behavioural space, we trained rats on a behavioural task that combines perceptual and value-guided decisions. An unbiased, model-free clustering analysis identified distinct groups of OFC neurons, each with a particular response profile in task-variable space. Applying a simple model of choice behaviour to these categorical response profiles revealed that each profile quantitatively corresponds to a specific decision variable, such as decision confidence. Additionally, we demonstrate that a connectivity-defined cell type, orbitofrontal neurons projecting to the striatum, carries a selective and temporally sustained representation of a single decision variable: integrated value. We propose that neurons in frontal cortex, as in other cortical regions, form a sparse and overcomplete representation of features relevant to the region's function, and that they distribute this information selectively to downstream regions to support behaviour.

Drifting neuronal representations: Bug or feature?

The brain displays a remarkable ability to sustain stable memories, allowing animals to execute precise behaviors or recall stimulus associations years after they were first learned. Yet, recent long-term recording experiments have revealed that single-neuron representations continuously change over time, contravening the classical assumption that learned features remain static. How do unstable neural codes support robust perception, memories, and actions? Here, we review recent experimental evidence for such representational drift across brain areas, as well as dissections of its functional characteristics and underlying mechanisms. We emphasize theoretical proposals for how drift need not only be a form of noise for which the brain must compensate. Rather, it can emerge from computationally beneficial mechanisms in hierarchical networks performing robust probabilistic computations.

Sensory noise predicts divisive reshaping of receptive fields.

In order to respond reliably to specific features of their environment, sensory neurons need to integrate multiple incoming noisy signals. Crucially, they also need to compete for the interpretation of those signals with other neurons representing similar features. The form that this competition should take depends critically on the noise corrupting these signals. In this study we show that for the type of noise commonly observed in sensory systems, whose variance scales with the mean signal, sensory neurons should selectively divide their input signals by their predictions, suppressing ambiguous cues while amplifying others. Any change in the stimulus context alters which inputs are suppressed, leading to a deep dynamic reshaping of neural receptive fields going far beyond simple surround suppression. Paradoxically, these highly variable receptive fields go alongside and are in fact required for an invariant representation of external sensory features. In addition to offering a normative account of context-dependent changes in sensory responses, perceptual inference in the presence of signal-dependent noise accounts for ubiquitous features of sensory neurons such as divisive normalization, gain control and contrast dependent temporal dynamics.

Interpretable deep learning for deconvolutional analysis of neural signals.

The widespread adoption of deep learning to build models that capture the dynamics of neural populations is typically based on "black-box" approaches that lack an interpretable link between neural activity and function. Here, we propose to apply algorithm unrolling, a method for interpretable deep learning, to design the architecture of sparse deconvolutional neural networks and obtain a direct interpretation of network weights in relation to stimulus-driven single-neuron activity through a generative model. We characterize our method, referred to as deconvolutional unrolled neural learning (DUNL), and show its versatility by applying it to deconvolve single-trial local signals across multiple brain areas and recording modalities. To exemplify use cases of our decomposition method, we uncover multiplexed salience and reward prediction error signals from midbrain dopamine neurons in an unbiased manner, perform simultaneous event detection and characterization in somatosensory thalamus recordings, and characterize the responses of neurons in the piriform cortex. Our work leverages the advances in interpretable deep learning to gain a mechanistic understanding of neural dynamics.

Multi-timescale reinforcement learning in the brain.

To thrive in complex environments, animals and artificial agents must learn to act adaptively to maximize fitness and rewards. Such adaptive behavior can be learned through reinforcement learning1, a class of algorithms that has been successful at training artificial agents2-6 and at characterizing the firing of dopamine neurons in the midbrain7-9. In classical reinforcement learning, agents discount future rewards exponentially according to a single time scale, controlled by the discount factor. Here, we explore the presence of multiple timescales in biological reinforcement learning. We first show that reinforcement agents learning at a multitude of timescales possess distinct computational benefits. Next, we report that dopamine neurons in mice performing two behavioral tasks encode reward prediction error with a diversity of discount time constants. Our model explains the heterogeneity of temporal discounting in both cue-evoked transient responses and slower timescale fluctuations known as dopamine ramps. Crucially, the measured discount factor of individual neurons is correlated across the two tasks suggesting that it is a cell-specific property. Together, our results provide a new paradigm to understand functional heterogeneity in dopamine neurons, a mechanistic basis for the empirical observation that humans and animals use non-exponential discounts in many situations10-14, and open new avenues for the design of more efficient reinforcement learning algorithms.

Neural Circuits for Fast Poisson Compressed Sensing in the Olfactory Bulb.

Within a single sniff, the mammalian olfactory system can decode the identity and concentration of odorants wafted on turbulent plumes of air. Yet, it must do so given access only to the noisy, dimensionally-reduced representation of the odor world provided by olfactory receptor neurons. As a result, the olfactory system must solve a compressed sensing problem, relying on the fact that only a handful of the millions of possible odorants are present in a given scene. Inspired by this principle, past works have proposed normative compressed sensing models for olfactory decoding. However, these models have not captured the unique anatomy and physiology of the olfactory bulb, nor have they shown that sensing can be achieved within the 100-millisecond timescale of a single sniff. Here, we propose a rate-based Poisson compressed sensing circuit model for the olfactory bulb. This model maps onto the neuron classes of the olfactory bulb, and recapitulates salient features of their connectivity and physiology. For circuit sizes comparable to the human olfactory bulb, we show that this model can accurately detect tens of odors within the timescale of a single sniff. We also show that this model can perform Bayesian posterior sampling for accurate uncertainty estimation. Fast inference is possible only if the geometry of the neural code is chosen to match receptor properties, yielding a distributed neural code that is not axis-aligned to individual odor identities. Our results illustrate how normative modeling can help us map function onto specific neural circuits to generate new hypotheses.

Apparent sunk cost effect in rational agents.

Rational decision makers aim to maximize their gains, but humans and other animals often fail to do so, exhibiting biases and distortions in their choice behavior. In a recent study of economic decisions, humans, mice, and rats were reported to succumb to the sunk cost fallacy, making decisions based on irrecoverable past investments to the detriment of expected future returns. We challenge this interpretation because it is subject to a statistical fallacy, a form of attrition bias, and the observed behavior can be explained without invoking a sunk cost-dependent mechanism. Using a computational model, we illustrate how a rational decision maker with a reward-maximizing decision strategy reproduces the reported behavioral pattern and propose an improved task design to dissociate sunk costs from fluctuations in decision valuation. Similar statistical confounds may be common in analyses of cognitive behaviors, highlighting the need to use causal statistical inference and generative models for interpretation.

Natural gradient enables fast sampling in spiking neural networks.

For animals to navigate an uncertain world, their brains need to estimate uncertainty at the timescales of sensations and actions. Sampling-based algorithms afford a theoretically-grounded framework for probabilistic inference in neural circuits, but it remains unknown how one can implement fast sampling algorithms in biologically-plausible spiking networks. Here, we propose to leverage the population geometry, controlled by the neural code and the neural dynamics, to implement fast samplers in spiking neural networks. We first show that two classes of spiking samplers-efficient balanced spiking networks that simulate Langevin sampling, and networks with probabilistic spike rules that implement Metropolis-Hastings sampling-can be unified within a common framework. We then show that careful choice of population geometry, corresponding to the natural space of parameters, enables rapid inference of parameters drawn from strongly-correlated high-dimensional distributions in both networks. Our results suggest design principles for algorithms for sampling-based probabilistic inference in spiking neural networks, yielding potential inspiration for neuromorphic computing and testable predictions for neurobiology.

Reinforcement biases subsequent perceptual decisions when confidence is low, a widespread behavioral phenomenon.

Learning from successes and failures often improves the quality of subsequent decisions. Past outcomes, however, should not influence purely perceptual decisions after task acquisition is complete since these are designed so that only sensory evidence determines the correct choice. Yet, numerous studies report that outcomes can bias perceptual decisions, causing spurious changes in choice behavior without improving accuracy. Here we show that the effects of reward on perceptual decisions are principled: past rewards bias future choices specifically when previous choice was difficult and hence decision confidence was low. We identified this phenomenon in six datasets from four laboratories, across mice, rats, and humans, and sensory modalities from olfaction and audition to vision. We show that this choice-updating strategy can be explained by reinforcement learning models incorporating statistical decision confidence into their teaching signals. Thus, reinforcement learning mechanisms are continually engaged to produce systematic adjustments of choices even in well-learned perceptual decisions in order to optimize behavior in an uncertain world.

The Neurobiology of Confidence: From Beliefs to Neurons.

How confident are you? As humans, aware of our subjective sense of confidence, we can readily answer. Knowing your level of confidence helps to optimize both routine decisions such as whether to go back and check if the front door was locked and momentous ones like finding a partner for life. Yet the inherently subjective nature of confidence has limited investigations by neurobiologists. Here, we provide an overview of recent advances in this field and lay out a conceptual framework that lets us translate psychological questions about subjective confidence into the language of neuroscience. We show how statistical notions of confidence provide a bridge between our subjective sense of confidence and confidence-guided behaviors in nonhuman animals, thus enabling the study of the underlying neurobiology. We discuss confidence as a core cognitive process that enables organisms to optimize behavior such as learning or resource allocation and that serves as the basis of metacognitive reasoning. These approaches place confidence on a solid footing and pave the way for a mechanistic understanding of how the brain implements confidence-based algorithms to guide behavior.