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We propose a computational neurology of movement based on the convergence of theoretical neurobiology and clinical neurology. A significant development in the former is the idea that we can frame brain function as a process of (active) inference, in which the nervous system makes predictions about its sensory data. These predictions depend upon an implicit predictive (generative) model used by the brain. This means neural dynamics can be framed as generating actions to ensure sensations are consistent with these predictions-and adjusting predictions when they are not. We illustrate the significance of this formulation for clinical neurology by simulating a clinical examination of the motor system using an upper limb coordination task. Specifically, we show how tendon reflexes emerge naturally under the right kind of generative model. Through simulated perturbations, pertaining to prior probabilities of this model's variables, we illustrate the emergence of hyperreflexia and pendular reflexes, reminiscent of neurological lesions in the corticospinal tract and cerebellum. We then turn to the computational lesions causing hypokinesia and deficits of coordination. This in silico lesion-deficit analysis provides an opportunity to revisit classic neurological dichotomies (e.g. pyramidal versus extrapyramidal systems) from the perspective of modern approaches to theoretical neurobiology-and our understanding of the neurocomputational architecture of movement control based on first principles. [ABSTRACT FROM AUTHOR]

Active inference is an approach to understanding behaviour that rests upon the idea that the brain uses an internal generative model to predict incoming sensory data. The fit between this model and data may be improved in two ways. The brain could optimise probabilistic beliefs about the variables in the generative model (i.e. perceptual inference). Alternatively, by acting on the world, it could change the sensory data, such that they are more consistent with the model. This implies a common objective function (variational free energy) for action and perception that scores the fit between an internal model and the world. We compare two free energy functionals for active inference in the framework of Markov decision processes. One of these is a functional of beliefs (i.e. probability distributions) about states and policies, but a function of observations, while the second is a functional of beliefs about all three. In the former (expected free energy), prior beliefs about outcomes are not part of the generative model (because they are absorbed into the prior over policies). Conversely, in the second (generalised free energy), priors over outcomes become an explicit component of the generative model. When using the free energy function, which is blind to future observations, we equip the generative model with a prior over policies that ensure preferred (i.e. priors over) outcomes are realised. In other words, if we expect to encounter a particular kind of outcome, this lends plausibility to those policies for which this outcome is a consequence. In addition, this formulation ensures that selected policies minimise uncertainty about future outcomes by minimising the free energy expected in the future. When using the free energy functional—that effectively treats future observations as hidden states—we show that policies are inferred or selected that realise prior preferences by minimising the free energy of future expectations. Interestingly, the form of posterior beliefs about policies (and associated belief updating) turns out to be identical under both formulations, but the quantities used to compute them are not. [ABSTRACT FROM AUTHOR]

Many physiological and pathological changes in brain function manifest in eye-movement control. As such, assessment of oculomotion is an invaluable part of a clinical examination and affords a non-invasive window on several key aspects of neuronal computation. While oculomotion is often used to detect deficits of the sort associated with vascular or neoplastic events; subtler (e.g. pharmacological) effects on neuronal processing also induce oculomotor changes. We have previously framed oculomotor control as part of active vision, namely, a process of inference comprising two distinct but related challenges. The first is inferring where to look, and the second is inferring how to implement the selected action. In this paper, we draw from recent theoretical work on the neuromodulatory control of active inference. This allows us to simulate the sort of changes we would expect in oculomotor behaviour, following pharmacological enhancement or suppression of key neuromodulators—in terms of deciding where to look and the ensuing trajectory of the eye movement itself. We focus upon the influence of cholinergic and GABAergic agents on the speed of saccades, and consider dopaminergic and noradrenergic effects on more complex, memory-guided, behaviour. In principle, a computational approach to understanding the relationship between pharmacology and oculomotor behaviour affords the opportunity to estimate the influence of a given pharmaceutical upon neuronal function, and to use this to optimise therapeutic interventions on an individual basis. [ABSTRACT FROM AUTHOR]

In recent years, the "planning as inference" paradigm has become central to the study of behaviour. The advance offered by this is the formalisation of motivation as a prior belief about "how I am going to act". This paper provides an overview of the factors that contribute to this prior. These are rooted in optimal experimental design, information theory, and statistical decision making. We unpack how these factors imply a functional architecture for motivated behaviour. This raises an important question: how can we put this architecture to work in the service of understanding observed neurobiological structure? To answer this question, we draw from established techniques in experimental studies of behaviour. Typically, these examine the influence of perturbations of the nervous system—which include pathological insults or optogenetic manipulations—to see their influence on behaviour. Here, we argue that the message passing that emerges from inferring what to do can be similarly perturbed. If a given perturbation elicits the same behaviours as a focal brain lesion, this provides a functional interpretation of empirical findings and an anatomical grounding for theoretical results. We highlight examples of this approach that influence different sorts of goal-directed behaviour, active learning, and decision making. Finally, we summarise their implications for the neuroanatomy of inferring what to do (and what not to). [ABSTRACT FROM AUTHOR]

How do we navigate a deeply structured world? Why are you reading this sentence first – and did you actually look at the fifth word? This review offers some answers by appealing to active inference based on deep temporal models. It builds on previous formulations of active inference to simulate behavioural and electrophysiological responses under hierarchical generative models of state transitions. Inverting these models corresponds to sequential inference, such that the state at any hierarchical level entails a sequence of transitions in the level below. The deep temporal aspect of these models means that evidence is accumulated over nested time scales, enabling inferences about narratives (i.e., temporal scenes). We illustrate this behaviour with Bayesian belief updating – and neuronal process theories – to simulate the epistemic foraging seen in reading. These simulations reproduce perisaccadic delay period activity and local field potentials seen empirically. Finally, we exploit the deep structure of these models to simulate responses to local (e.g., font type) and global (e.g., semantic) violations; reproducing mismatch negativity and P300 responses respectively. [ABSTRACT FROM AUTHOR]

How do we navigate a deeply structured world? Why are you reading this sentence first – and did you actually look at the fifth word? This review offers some answers by appealing to active inference based on deep temporal models. It builds on previous formulations of active inference to simulate behavioural and electrophysiological responses under hierarchical generative models of state transitions. Inverting these models corresponds to sequential inference, such that the state at any hierarchical level entails a sequence of transitions in the level below. The deep temporal aspect of these models means that evidence is accumulated over nested time scales, enabling inferences about narratives (i.e., temporal scenes). We illustrate this behaviour with Bayesian belief updating – and neuronal process theories – to simulate the epistemic foraging seen in reading. These simulations reproduce perisaccadic delay period activity and local field potentials seen empirically. Finally, we exploit the deep structure of these models to simulate responses to local (e.g., font type) and global (e.g., semantic) violations; reproducing mismatch negativity and P300 responses respectively. [ABSTRACT FROM AUTHOR]

Delusions are, by popular definition, false beliefs that are held with certainty and resistant to contradictory evidence. They seem at odds with the notion that the brain at least approximates Bayesian inference. This is especially the case in schizophrenia, a disorder thought to relate to decreased - rather than increased - certainty in the brain's model of the world. We use an active inference Markov decision process model (a Bayes-optimal decision-making agent) to perform a simple task involving social and non-social inferences. We show that even moderate changes in some model parameters - decreasing confidence in sensory input and increasing confidence in states implied by its own (especially habitual) actions - can lead to delusions as defined above. Incorporating affect in the model increases delusions, specifically in the social domain. The model also reproduces some classic psychological effects, including choice-induced preference change, and an optimism bias in inferences about oneself. A key observation is that no change in a single parameter is both necessary and sufficient for delusions; rather, delusions arise due to conditional dependencies that create 'basins of attraction' which trap Bayesian beliefs. Simulating the effects of antidopaminergic antipsychotics - by reducing the model's confidence in its actions - demonstrates that the model can escape from these attractors, through this synthetic pharmacotherapy. [ABSTRACT FROM AUTHOR]