Toward Biochemical Probabilistic Computation

International Journal of Approximate Reasoning, 2017

Living organisms survive and multiply even though they have uncertain and incomplete information about their environment and imperfect models to predict the consequences of their actions. Bayesian models have been proposed to face this challenge. Indeed, Bayesian inference is a way to do optimal reasoning when only uncertain and incomplete information is available. Various perceptive, sensory-motor, and cognitive functions have been successfully modeled this way. However, the biological mechanisms allowing animals and humans to represent and to compute probability distributions are not known. It has been proposed that neurons and assemblies of neurons could be the appropriate scale to search for clues to probabilistic reasoning. In contrast, in this paper, we propose that interacting populations of macromolecules and diffusible messengers can perform probabilistic computation. This suggests that probabilistic reasoning, based on cellular signaling pathways, is a fundamental skill of living organisms available to the simplest unicellular organisms as well as the most complex brains.

Nature Neuroscience, 2009

We propose that synapses may be the workhorse of the neuronal computations that underlie probabilistic reasoning. We built a neural circuit model for probabilistic inference in which information provided by different sensory cues must be integrated and the predictive powers of individual cues about an outcome are deduced through experience. We found that bounded synapses naturally compute, through reward-dependent plasticity, the posterior probability that a choice alternative is correct given that a cue is presented. Furthermore, a decision circuit endowed with such synapses makes choices on the basis of the summed log posterior odds and performs near-optimal cue combination. The model was validated by reproducing salient observations of, and provides insights into, a monkey experiment using a categorization task. Our model thus suggests a biophysical instantiation of the Bayesian decision rule, while predicting important deviations from it similar to the 'base-rate neglect' observed in human studies when alternatives have unequal prior probabilities.

Frontiers in Synaptic Neuroscience, 2014

Learning and memory operations in neural circuits are believed to involve molecular cascades of synaptic and nonsynaptic changes that lead to a diverse repertoire of dynamical phenomena at higher levels of processing. Hebbian and homeostatic plasticity, neuromodulation, and intrinsic excitability all conspire to form and maintain memories. But it is still unclear how these seemingly redundant mechanisms could jointly orchestrate learning in a more unified system. To this end, a Hebbian learning rule for spiking neurons inspired by Bayesian statistics is proposed. In this model, synaptic weights and intrinsic currents are adapted on-line upon arrival of single spikes, which initiate a cascade of temporally interacting memory traces that locally estimate probabilities associated with relative neuronal activation levels. Trace dynamics enable synaptic learning to readily demonstrate a spike-timing dependence, stably return to a set-point over long time scales, and remain competitive despite this stability. Beyond unsupervised learning, linking the traces with an external plasticity-modulating signal enables spike-based reinforcement learning. At the postsynaptic neuron, the traces are represented by an activity-dependent ion channel that is shown to regulate the input received by a postsynaptic cell and generate intrinsic graded persistent firing levels. We show how spike-based Hebbian-Bayesian learning can be performed in a simulated inference task using integrate-and-fire (IAF) neurons that are Poisson-firing and background-driven, similar to the preferred regime of cortical neurons. Our results support the view that neurons can represent information in the form of probability distributions, and that probabilistic inference could be a functional by-product of coupled synaptic and nonsynaptic mechanisms operating over several timescales. The model provides a biophysical realization of Bayesian computation by reconciling several observed neural phenomena whose functional effects are only partially understood in concert.

Trends in Cognitive Sciences

2005

We propose a new interpretation of spiking neurons as Bayesian integrators accumulating evidence over time about events in the external world or the body, and communicating to other neurons their certainties about these events. In this model, spikes signal the occurrence of new information, i.e. what cannot be predicted from the past activity. As a result, firing statistics are close to Poisson, albeit providing a deterministic representation of probabilities. We proceed to develop a theory of Bayesian inference in spiking neural networks, recurrent interactions implementing a variant of belief propagation. Many perceptual and motor tasks performed by the central nervous system are probabilistic, and can be described in a Bayesian framework [4, 3]. A few important but hidden properties, such as direction of motion, or appropriate motor commands, are inferred from many noisy, local and ambiguous sensory cues. These evidences are combined with priors about the sensory world and body. Importantly, because most of these inferences should lead to quick and irreversible decisions in a perpetually changing world, noisy cues have to be integrated on-line, but in a way that takes into account unpredictable events, such as a sudden change in motion direction or the appearance of a new stimulus.

Neurocomputing, 2013

In this paper, the presynaptic rule, a classical model of synaptic reinforcement, is revisited. It is shown that this model is capable of reproducing recently discovered properties of biological synapses such as synaptic directionality, and metaplasticity of the long-term potentiation threshold. With slight modifications, the presynaptic model also reproduces metaplasticity of the long-term depression threshold and Artola, Bröcher and Singer's experimental model. Two asymptotically equivalent approaches were adopted for this analysis, one with firing rates and another with conditional probabilities. Although both approximations are consistent with biological properties, the results obtained by the probabilistic approach are qualitatively closer to biological experimental results.

Journal of theoretical biology, 1999

This paper analyses relationships between probabilities of events happening in biological systems (or probabilistic disposition of systems) and cognitive properties of biological entities comprising such systems. Two kinds of cognitive properties are identi"ed as relevant to the current problem: the ability to respond di!erently against di!erent con"gurations of the environment (discriminability of cognition), and the ability to make an appropriate response to maintain a particular relation with the environment (selectivity of cognition). A basic framework bridging the two features of living systems, probabilistic disposition and the cognitive properties, is presented towards a general theory explaining the process generating probabilities of biological events. In this framework, a deterministic model of a system of entities is developed, in which objects are described as subjects that cognize events (i.e. entities as cognizers). Cognition is used in a wider sense, including not only biotic but also abiotic, and cognizers are conceptually distinguished from the meta-observer who describes the system externally. Based on this perspective, this paper seeks to explicate how events can occur in an uncertain, probabilistic manner, if observed from a cognizer viewpoint, even under a deterministic system. Each cognizer is identi"ed with both the set of states that are actually taken, and its motion function which maps its state uniquely to a successor state depending on the current states of itself and of the rest of cognizers constituting the system. The model analysis reveals that the cognitive properties, discriminability and selectivity, of a cognizer can contribute to determining the probability of an event encountered by the cognizer itself*in particular, discrimination reducing the uncertainty in events occurrence for the cognizer. Biological implication of this result is discussed focusing on the concept of the probability of survival and reproduction.

Decision formation recruits many brain regions, but the procedure they jointly execute is unknown. Here we characterize its essential composition, using as a framework a novel recursive Bayesian algorithm that makes decisions based on spike-trains with the statistics of those in sensory cortex (MT). Using it to simulate the random-dot-motion task, we demonstrate it quantitatively replicates the choice behaviour of monkeys, whilst predicting losses of otherwise usable information from MT. Its architecture maps to the recurrent cortico-basal-ganglia-thalamo-cortical loops, whose components are all implicated in decision-making. We show that the dynamics of its mapped computations match those of neural activity in the sensorimotor cortex and striatum during decisions, and forecast those of basal ganglia output and thalamus. This also predicts which aspects of neural dynamics are and are not part of inference. Our single-equation algorithm is probabilistic, distributed, recursive, and parallel. Its success at capturing anatomy, behaviour, and electrophysiology suggests that the mechanism implemented by the brain has these same characteristics.

Advances in neural …, 2005

As animals interact with their environments, they must constantly update estimates about their states. Bayesian models combine prior probabilities, a dynamical model and sensory evidence to update estimates optimally. These models are consistent with the results of many diverse psychophysical studies. However, little is known about the neural representation and manipulation of such Bayesian information, particularly in populations of spiking neurons. We consider this issue, suggesting a model based on standard neural architecture and activations. We illustrate the approach on a simple random walk example, and apply it to a sensorimotor integration task that provides a particularly compelling example of dynamic probabilistic computation.

Molecules, 2021

Human interaction with the world is dominated by uncertainty. Probability theory is a valuable tool to face such uncertainty. According to the Bayesian definition, probabilities are personal beliefs. Experimental evidence supports the notion that human behavior is highly consistent with Bayesian probabilistic inference in both the sensory and motor and cognitive domain. All the higher-level psychophysical functions of our brain are believed to take the activities of interconnected and distributed networks of neurons in the neocortex as their physiological substrate. Neurons in the neocortex are organized in cortical columns that behave as fuzzy sets. Fuzzy sets theory has embraced uncertainty modeling when membership functions have been reinterpreted as possibility distributions. The terms of Bayes’ formula are conceivable as fuzzy sets and Bayes’ inference becomes a fuzzy inference. According to the QBism, quantum probabilities are also Bayesian. They are logical constructs rather ...