Contextual fear conditioning is an experimental framework widely used to investigate how aversive experiences affect the valence an animal associates with an environment. While the initial formation of associative context-fear memories is well studied - dependent on plasticity in hippocampus and amygdala - the neural mechanisms underlying their subsequent consolidation remain less understood. Recent evidence suggests that the recall of contextual fear memories shifts from hippocampal-amygdalar to amygdalo-cortical networks as they age. This transition is thought to rely on sleep. In particular, neural replay during hippocampal sharp-wave ripple events seems crucial, though open questions regarding the involved neural interactions remain. Here, we propose a biologically informed neural network model of context-fear learning. It expands the scope of previous models through the addition of a sleep phase. Hippocampal representations of context, formed during wakefulness, are replayed in conjunction with cortical and amygdalar activity patterns to establish long-term fear memories. In addition, valence-coding synapses within the amygdala are subject to homeostatic plasticity overnight, which stabilizes fear associations and regulates the fear circuitry's synaptic density. The model reproduces experimentally observed phenomena, including context-dependent fear renewal and time-dependent increases in fear generalisation. Our model integrates mechanisms of fear learning, systems consolidation and synaptic homeostasis to provide a unified account of how contextual fear memories form and evolve over time. Our framework yields testable predictions about how disruptions in synaptic homeostasis may promote a persistent, fear-sensitized state. Accounting for neural mechanisms that reshape fear memories after their formation is a step towards bridging computational models of fear learning and the mechanisms behind trauma and anxiety disorders.

Autism spectrum disorders have been proposed to arise from impairments in the probabilistic integration of prior knowledge with sensory inputs. Circular inference is one such possible impairment, in which excitation-to-inhibition imbalances in the cerebral cortex cause the reverberation and amplification of prior beliefs and sensory information. Recent empirical work has associated circular inference with the clinical dimensions of schizophrenia. Inhibition impairments have also been observed in autism, suggesting that signal reverberation might be present in that condition as well. In this study, we collected data from 21 participants with self-reported diagnoses of autism spectrum disorders and 155 participants with a broad range of autistic traits in an online probabilistic decision-making task (the fisher task). We used previously established Bayesian models to investigate possible associations between autistic traits or autism and circular inference. There was no correlation between prior or likelihood reverberation and autistic traits across the whole sample. Similarly, no differences in any of the circular inference model parameters were found between autistic participants and those with no diagnosis. Furthermore, participants incorporated information from both priors and likelihoods in their decisions, with no relationship between their weights and psychiatric traits, contrary to what common theories for both autism and schizophrenia would suggest. These findings suggest that there is no increased signal reverberation in autism, despite the known presence of excitation-to-inhibition imbalances. They can be used to further contrast and refine the Bayesian theories of schizophrenia and autism, revealing a divergence in the computational mechanisms underlying the two conditions.

Optimists hold positive a priori beliefs about the future. In Bayesian statistical theory, a priori beliefs can be overcome by experience. However, optimistic beliefs can at times appear surprisingly resistant to evidence, suggesting that optimism might also influence how new information is selected and learned. Here, we use a novel Pavlovian conditioning task, embedded in a normative framework, to directly assess how trait optimism, as classically measured using self-report questionnaires, influences choices between visual targets, by learning about their association with reward progresses. We find that trait optimism relates to an a priori belief about the likelihood of rewards, but not losses, in our task. Critically, this positive belief behaves like a probabilistic prior, i.e. its influence reduces with increasing experience. Contrary to findings in the literature related to unrealistic optimism and self-beliefs, it does not appear to influence the iterative learning process directly.

Attention causes diverse changes to visual neuron responses, including alterations in receptive field structure, and firing rates. A common theoretical approach to investigate why sensory neurons behave as they do is based on the efficient coding hypothesis: that sensory processing is optimized toward the statistics of the received input. We extend this approach to account for the influence of task demands, hypothesizing that the brain learns a probabilistic model of both the sensory input and reward received for performing different actions. Attention-dependent changes to neural responses reflect optimization of this internal model to deal with changes in the sensory environment (stimulus statistics) and behavioral demands (reward statistics). We use this framework to construct a simple model of visual processing that is able to replicate a number of attention-dependent changes to the responses of neurons in the midlevel visual cortices. The model is consistent with and provides a normative explanation for recent divisive normalization models of attention (Reynolds & Heeger, 2009).

Several theories propose that the cortex implements an internal model to explain, predict, and learn about sensory data, but the nature of this model is unclear. One condition that could be highly informative here is Charles Bonnet syndrome (CBS), where loss of vision leads to complex, vivid visual hallucinations of objects, people, and whole scenes. CBS could be taken as indication that there is a generative model in the brain, specifically one that can synthesise rich, consistent visual representations even in the absence of actual visual input. The processes that lead to CBS are poorly understood. Here, we argue that a model recently introduced in machine learning, the deep Boltzmann machine (DBM), could capture the relevant aspects of (hypothetical) generative processing in the cortex. The DBM carries both the semantics of a probabilistic generative model and of a neural network. The latter allows us to model a concrete neural mechanism that could underlie CBS, namely, homeostatic regulation of neuronal activity. We show that homeostatic plasticity could serve to make the learnt internal model robust against e.g. degradation of sensory input, but overcompensate in the case of CBS, leading to hallucinations. We demonstrate how a wide range of features of CBS can be explained in the model and suggest a potential role for the neuromodulator acetylcholine. This work constitutes the first concrete computational model of CBS and the first application of the DBM as a model in computational neuroscience. Our results lend further credence to the hypothesis of a generative model in the brain.

The precision of the neural code is commonly investigated using two families of statistical measures: Shannon mutual information and derived quantities when investigating very small populations of neurons and Fisher information when studying large populations. These statistical tools are no longer the preserve of theorists and are being applied by experimental research groups in the analysis of empirical data. Although the relationship between information-theoretic and Fisher-based measures in the limit of infinite populations is relatively well understood, how these measures compare in finite-size populations has not yet been systematically explored. We aim to close this gap. We are particularly interested in understanding which stimuli are best encoded by a given neuron within a population and how this depends on the chosen measure. We use a novel Monte Carlo approach to compute a stimulus-specific decomposition of the mutual information (the SSI) for populations of up to 256 neurons and show that Fisher information can be used to accurately estimate both mutual information and SSI for populations of the order of 100 neurons, even in the presence of biologically realistic variability, noise correlations, and experimentally relevant integration times. According to both measures, the stimuli that are best encoded are those falling at the flanks of the neuron's tuning curve. In populations of fewer than around 50 neurons, however, Fisher information can be misleading.

It has been argued that perceptual multistability reflects probabilistic inference performed by the brain when sensory input is ambiguous. Alternatively, more traditional explanations of multistability refer to low-level mechanisms such as neuronal adaptation. We employ a Deep Boltzmann Machine (DBM) model of cortical processing to demonstrate that these two different approaches can be combined in the same framework. Based on recent developments in machine learning, we show how neuronal adaptation can be understood as a mechanism that improves probabilistic, sampling-based inference. Using the ambiguous Necker cube image, we analyze the perceptual switching exhibited by the model. We also examine the influence of spatial attention, and explore how binocular rivalry can be modeled with the same approach. Our work joins earlier studies in demonstrating how the principles underlying DBMs relate to cortical processing, and offers novel perspectives on the neural implementation of approximate probabilistic inference in the brain.

The Charles Bonnet Syndrome (CBS) is characterized by complex vivid visual hallucinations in people with, primarily, eye diseases and no other neurological pathology. We present a Deep Boltzmann Machine model of CBS, exploring two core hypotheses: First, that the visual cortex learns a generative or predictive model of sensory input, thus explaining its capability to generate internal imagery. And second, that homeostatic mechanisms stabilize neuronal activity levels, leading to hallucinations being formed when input is lacking. We reproduce a variety of qualitative findings in CBS. We also introduce a modification to the DBM that allows us to model a possible role of acetylcholine in CBS as mediating the balance of feed-forward and feed-back processing. Our model might provide new insights into CBS and also demonstrates that generative frameworks are promising as hypothetical models of cortical learning and perception.

Neural activity and perception are both affected by sensory history. The work presented here explores the relationship between the physiological effects of adaptation and their perceptual consequences. Perception is modeled as arising from an encoder-decoder cascade, in which the encoder is defined by the probabilistic response of a population of neurons, and the decoder transforms this population activity into a perceptual estimate. Adaptation is assumed to produce changes in the encoder, and we examine the conditions under which the decoder behavior is consistent with observed perceptual effects in terms of both bias and discriminability. We show that for all decoders, discriminability is bounded from below by the inverse Fisher information. Estimation bias, on the other hand, can arise for a variety of different reasons and can range from zero to substantial. We specifically examine biases that arise when the decoder is fixed, "unaware" of the changes in the encoding population (as opposed to "aware" of the adaptation and changing accordingly). We simulate the effects of adaptation on two well-studied sensory attributes, motion direction and contrast, assuming a gain change description of encoder adaptation. Although we cannot uniquely constrain the source of decoder bias, we find for both motion and contrast that an "unaware" decoder that maximizes the likelihood of the percept given by the preadaptation encoder leads to predictions that are consistent with behavioral data. This model implies that adaptation-induced biases arise as a result of temporary suboptimality of the decoder.

Several recent models have proposed the use of precise timing of spikes for cortical computation. Such models rely on growing experimental evidence that neurons in the thalamus as well as many primary sensory cortical areas respond to stimuli with remarkable temporal precision. Models of computation based on spike timing, where the output of the network is a function not only of the input but also of an independently initializable internal state of the network, must, however, satisfy a critical constraint: the dynamics of the network should not be sensitive to initial conditions. We have previously developed an abstract dynamical system for networks of spiking neurons that has allowed us to identify the criterion for the stationary dynamics of a network to be sensitive to initial conditions. Guided by this criterion, we analyzed the dynamics of several recurrent cortical architectures, including one from the orientation selectivity literature. Based on the results, we conclude that under conditions of sustained, Poisson-like, weakly correlated, low to moderate levels of internal activity as found in the cortex, it is unlikely that recurrent cortical networks can robustly generate precise spike trajectories, that is, spatiotemporal patterns of spikes precise to the millisecond timescale.