Reliability of dynamic causal modelling of resting-state magnetoencephalography.

This study assesses the reliability of resting-state dynamic causal modelling (DCM) of magnetoencephalography (MEG) under conductance-based canonical microcircuit models, in terms of both posterior parameter estimates and model evidence. We use resting-state MEG data from two sessions, acquired 2 weeks apart, from a cohort with high between-subject variance arising from Alzheimer's disease. Our focus is not on the effect of disease, but on the reliability of the methods (as within-subject between-session agreement), which is crucial for future studies of disease progression and drug intervention. To assess the reliability of first-level DCMs, we compare model evidence associated with the covariance among subject-specific free energies (i.e., the 'quality' of the models) with versus without interclass correlations. We then used parametric empirical Bayes (PEB) to investigate the differences between the inferred DCM parameter probability distributions at the between subject level. Specifically, we examined the evidence for or against parameter differences (i) within-subject, within-session, and between-epochs; (ii) within-subject between-session; and (iii) within-site between-subjects, accommodating the conditional dependency among parameter estimates. We show that for data acquired close in time, and under similar circumstances, more than 95% of inferred DCM parameters are unlikely to differ, speaking to mutual predictability over sessions. Using PEB, we show a reciprocal relationship between a conventional definition of 'reliability' and the conditional dependency among inferred model parameters. Our analyses confirm the reliability and reproducibility of the conductance-based DCMs for resting-state neurophysiological data. In this respect, the implicit generative modelling is suitable for interventional and longitudinal studies of neurological and psychiatric disorders.

Narrative as active inference: an integrative account of cognitive and social functions in adaptation.

While the ubiquity and importance of narratives for human adaptation is widely recognized, there is no integrative framework for understanding the roles of narrative in human adaptation. Research has identified several cognitive and social functions of narratives that are conducive to well-being and adaptation as well as to coordinated social practices and enculturation. In this paper, we characterize the cognitive and social functions of narratives in terms of active inference, to support the claim that one of the main adaptive functions of narrative is to generate more useful (i.e., accurate, parsimonious) predictions for the individual, as well as to coordinate group action (over multiple timescales) through shared predictions about collective behavior. Active inference is a theory that depicts the fundamental tendency of living organisms to adapt by proactively inferring the causes of their sensations (including their own actions). We review narrative research on identity, event segmentation, episodic memory, future projections, storytelling practices, enculturation, and master narratives. We show how this research dovetails with the active inference framework and propose an account of the cognitive and social functions of narrative that emphasizes that narratives are for the future-even when they are focused on recollecting or recounting the past. Understanding narratives as cognitive and cultural tools for mutual prediction in social contexts can guide research on narrative in adaptive behavior and psychopathology, based on a parsimonious mechanistic model of some of the basic adaptive functions of narrative.

Two distinct networks for encoding goals and forms of action: An effective connectivity study.

Goal-directed actions are characterized by two main features: the content (i.e., the action goal) and the form, called vitality forms (VF) (i.e., how actions are executed). It is well established that both the action content and the capacity to understand the content of another's action are mediated by a network formed by a set of parietal and frontal brain areas. In contrast, the neural bases of action forms (e.g., gentle or rude actions) have not been characterized. However, there are now studies showing that the observation and execution of actions endowed with VF activate, in addition to the parieto-frontal network, the dorso-central insula (DCI). In the present study, we established-using dynamic causal modeling (DCM)-the direction of information flow during observation and execution of actions endowed with gentle and rude VF in the human brain. Based on previous fMRI studies, the selected nodes for the DCM comprised the posterior superior temporal sulcus (pSTS), the inferior parietal lobule (IPL), the premotor cortex (PM), and the DCI. Bayesian model comparison showed that, during action observation, two streams arose from pSTS: one toward IPL, concerning the action goal, and one toward DCI, concerning the action vitality forms. During action execution, two streams arose from PM: one toward IPL, concerning the action goal and one toward DCI concerning action vitality forms. This last finding opens an interesting question concerning the possibility to elicit VF in two distinct ways: cognitively (from PM to DCI) and affectively (from DCI to PM).

Forgetting ourselves in flow: an active inference account of flow states and how we experience ourselves within them.

Flow has been described as a state of optimal performance, experienced universally across a broad range of domains: from art to athletics, gaming to writing. However, its phenomenal characteristics can, at first glance, be puzzling. Firstly, individuals in flow supposedly report a loss of self-awareness, even though they perform in a manner which seems to evince their agency and skill. Secondly, flow states are felt to be effortless, despite the prerequisite complexity of the tasks that engender them. In this paper, we unpick these features of flow, as well as others, through the active inference framework, which posits that action and perception are forms of active Bayesian inference directed at sustained self-organisation; i.e., the minimisation of variational free energy. We propose that the phenomenology of flow is rooted in the deployment of high precision weight over (i) the expected sensory consequences of action and (ii) beliefs about how action will sequentially unfold. This computational mechanism thus draws the embodied cognitive system to minimise the ensuing (i.e., expected) free energy through the exploitation of the pragmatic affordances at hand. Furthermore, given the challenging dynamics the flow-inducing situation presents, attention must be wholly focussed on the unfolding task whilst counterfactual planning is restricted, leading to the attested loss of the sense of self-as-object. This involves the inhibition of both the sense of self as a temporally extended object and higher-order, meta-cognitive forms of self-conceptualisation. Nevertheless, we stress that self-awareness is not entirely lost in flow. Rather, it is pre-reflective and bodily. Our approach to bodily-action-centred phenomenology can be applied to similar facets of seemingly agentive experience beyond canonical flow states, providing insights into the mechanisms of so-called selfless experiences, embodied expertise and wellbeing.

Climate change and disorders of the nervous system.

Anthropogenic climate change is affecting people's health, including those with neurological and psychiatric diseases. Currently, making inferences about the effect of climate change on neurological and psychiatric diseases is challenging because of an overall sparsity of data, differing study methods, paucity of detail regarding disease subtypes, little consideration of the effect of individual and population genetics, and widely differing geographical locations with the potential for regional influences. However, evidence suggests that the incidence, prevalence, and severity of many nervous system conditions (eg, stroke, neurological infections, and some mental health disorders) can be affected by climate change. The data show broad and complex adverse effects, especially of temperature extremes to which people are unaccustomed and wide diurnal temperature fluctuations. Protective measures might be possible through local forecasting. Few studies project the future effects of climate change on brain health, hindering policy developments. Robust studies on the threats from changing climate for people who have, or are at risk of developing, disorders of the nervous system are urgently needed.

Collective behavior from surprise minimization.

Collective motion is ubiquitous in nature; groups of animals, such as fish, birds, and ungulates appear to move as a whole, exhibiting a rich behavioral repertoire that ranges from directed movement to milling to disordered swarming. Typically, such macroscopic patterns arise from decentralized, local interactions among constituent components (e.g., individual fish in a school). Preeminent models of this process describe individuals as self-propelled particles, subject to self-generated motion and "social forces" such as short-range repulsion and long-range attraction or alignment. However, organisms are not particles; they are probabilistic decision-makers. Here, we introduce an approach to modeling collective behavior based on active inference. This cognitive framework casts behavior as the consequence of a single imperative: to minimize surprise. We demonstrate that many empirically observed collective phenomena, including cohesion, milling, and directed motion, emerge naturally when considering behavior as driven by active Bayesian inference-without explicitly building behavioral rules or goals into individual agents. Furthermore, we show that active inference can recover and generalize the classical notion of social forces as agents attempt to suppress prediction errors that conflict with their expectations. By exploring the parameter space of the belief-based model, we reveal nontrivial relationships between the individual beliefs and group properties like polarization and the tendency to visit different collective states. We also explore how individual beliefs about uncertainty determine collective decision-making accuracy. Finally, we show how agents can update their generative model over time, resulting in groups that are collectively more sensitive to external fluctuations and encode information more robustly.

Measurement of the Mapping between Intracranial EEG and fMRI Recordings in the Human Brain.

There are considerable gaps in our understanding of the relationship between human brain activity measured at different temporal and spatial scales. Here, electrocorticography (ECoG) measures were used to predict functional MRI changes in the sensorimotor cortex in two brain states: at rest and during motor performance. The specificity of this relationship to spatial co-localisation of the two signals was also investigated. We acquired simultaneous ECoG-fMRI in the sensorimotor cortex of three patients with epilepsy. During motor activity, high gamma power was the only frequency band where the electrophysiological response was co-localised with fMRI measures across all subjects. The best model of fMRI changes across states was its principal components, a parsimonious description of the entire ECoG spectrogram. This model performed much better than any others that were based either on the classical frequency bands or on summary measures of cross-spectral changes. The region-specific fMRI signal is reflected in spatially and spectrally distributed EEG activity.

Targeting suicidal ideation in major depressive disorder with MRI-navigated Stanford accelerated intelligent neuromodulation therapy.

High suicide risk represents a serious problem in patients with major depressive disorder (MDD), yet treatment options that could safely and rapidly ameliorate suicidal ideation remain elusive. Here, we tested the feasibility and preliminary efficacy of the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) in reducing suicidal ideation in patients with MDD. Thirty-two MDD patients with moderate to severe suicidal ideation participated in the current study. Suicidal ideation and depression symptoms were assessed before and after 5 days of open-label SAINT. The neural pathways supporting rapid-acting antidepressant and suicide prevention effects were identified with dynamic causal modelling based on resting-state functional magnetic resonance imaging. We found that 5 days of SAINT effectively alleviated suicidal ideation in patients with MDD with a high response rate of 65.63%. Moreover, the response rates achieved 78.13% and 90.63% with 2 weeks and 4 weeks after SAINT, respectively. In addition, we found that the suicide prevention effects of SAINT were associated with the effective connectivity involving the insula and hippocampus, while the antidepressant effects were related to connections of the subgenual anterior cingulate cortex (sgACC). These results show that SAINT is a rapid-acting and effective way to reduce suicidal ideation. Our findings further suggest that distinct neural mechanisms may contribute to the rapid-acting effects on the relief of suicidal ideation and depression, respectively.

Federated inference and belief sharing.

This paper concerns the distributed intelligence or federated inference that emerges under belief-sharing among agents who share a common world-and world model. Imagine, for example, several animals keeping a lookout for predators. Their collective surveillance rests upon being able to communicate their beliefs-about what they see-among themselves. But, how is this possible? Here, we show how all the necessary components arise from minimising free energy. We use numerical studies to simulate the generation, acquisition and emergence of language in synthetic agents. Specifically, we consider inference, learning and selection as minimising the variational free energy of posterior (i.e., Bayesian) beliefs about the states, parameters and structure of generative models, respectively. The common theme-that attends these optimisation processes-is the selection of actions that minimise expected free energy, leading to active inference, learning and model selection (a.k.a., structure learning). We first illustrate the role of communication in resolving uncertainty about the latent states of a partially observed world, on which agents have complementary perspectives. We then consider the acquisition of the requisite language-entailed by a likelihood mapping from an agent's beliefs to their overt expression (e.g., speech)-showing that language can be transmitted across generations by active learning. Finally, we show that language is an emergent property of free energy minimisation, when agents operate within the same econiche. We conclude with a discussion of various perspectives on these phenomena; ranging from cultural niche construction, through federated learning, to the emergence of complexity in ensembles of self-organising systems.

Leveraging Julia's automated differentiation and symbolic computation to increase spectral DCM flexibility and speed.

Using neuroimaging and electrophysiological data to infer neural parameter estimations from theoretical circuits requires solving the inverse problem. Here, we provide a new Julia language package designed to i) compose complex dynamical models in a simple and modular way with ModelingToolkit.jl, ii) implement parameter fitting based on spectral dynamic causal modeling (sDCM) using the Laplace approximation, analogous to MATLAB implementation in SPM12, and iii) leverage Julia's unique strengths to increase accuracy and speed by employing Automatic Differentiation during the fitting procedure. To illustrate the utility of our flexible modular approach, we provide a method to improve correction for fMRI scanner field strengths (1.5T, 3T, 7T) when fitting models to real data.

Conceptual foundations of physiological regulation incorporating the free energy principle and self-organized criticality.

Bettinger, J. S., K. J. Friston. Conceptual Foundations of Physiological Regulation incorporating the Free Energy Principle & Self-Organized Criticality. NEUROSCI BIOBEHAV REV 23(x) 144-XXX, 2022. Since the late nineteen-nineties, the concept of homeostasis has been contextualized within a broader class of "allostatic" dynamics characterized by a wider-berth of causal factors including social, psychological and environmental entailments; the fundamental nature of integrated brain-body dynamics; plus the role of anticipatory, top-down constraints supplied by intrinsic regulatory models. Many of these evidentiary factors are integral in original descriptions of homeostasis; subsequently integrated; and/or cite more-general operating principles of self-organization. As a result, the concept of allostasis may be generalized to a larger category of variational systems in biology, engineering and physics in terms of advances in complex systems, statistical mechanics and dynamics involving heterogenous (hierarchical/heterarchical, modular) systems like brain-networks and the internal milieu. This paper offers a three-part treatment. 1) interpret "allostasis" to emphasize a variational and relational foundation of physiological stability; 2) adapt the role of allostasis as "stability through change" to include a "return to stability" and 3) reframe the model of homeostasis with a conceptual model of criticality that licenses the upgrade to variational dynamics.

Degeneracy in the neurological model of auditory speech repetition.

Both classic and contemporary models of auditory word repetition involve at least four left hemisphere regions: primary auditory cortex for processing sounds; pSTS (within Wernicke's area) for processing auditory images of speech; pOp (within Broca's area) for processing motor images of speech; and primary motor cortex for overt speech articulation. Previous functional-MRI (fMRI) studies confirm that auditory repetition activates these regions, in addition to many others. Crucially, however, contemporary models do not specify how regions interact and drive each other during auditory repetition. Here, we used dynamic causal modelling, to test the functional interplay among the four core brain regions during single auditory word and pseudoword repetition. Our analysis is grounded in the principle of degeneracy-i.e., many-to-one structure-function relationships-where multiple neural pathways can execute the same function. Contrary to expectation, we found that, for both word and pseudoword repetition, (i) the effective connectivity between pSTS and pOp was predominantly bidirectional and inhibitory; (ii) activity in the motor cortex could be driven by either pSTS or pOp; and (iii) the latter varied both within and between individuals. These results suggest that different neural pathways can support auditory speech repetition. This degeneracy may explain resilience to functional loss after brain damage.

Establishing brain states in neuroimaging data.

The definition of a brain state remains elusive, with varying interpretations across different sub-fields of neuroscience-from the level of wakefulness in anaesthesia, to activity of individual neurons, voltage in EEG, and blood flow in fMRI. This lack of consensus presents a significant challenge to the development of accurate models of neural dynamics. However, at the foundation of dynamical systems theory lies a definition of what constitutes the 'state' of a system-i.e., a specification of the system's future. Here, we propose to adopt this definition to establish brain states in neuroimaging timeseries by applying Dynamic Causal Modelling (DCM) to low-dimensional embedding of resting and task condition fMRI data. We find that ~90% of subjects in resting conditions are better described by first-order models, whereas ~55% of subjects in task conditions are better described by second-order models. Our work calls into question the status quo of using first-order equations almost exclusively within computational neuroscience and provides a new way of establishing brain states, as well as their associated phase space representations, in neuroimaging datasets.

Attentional effects on local V1 microcircuits explain selective V1-V4 communication.

Selective attention implements preferential routing of attended stimuli, likely through increasing the influence of the respective synaptic inputs on higher-area neurons. As the inputs of competing stimuli converge onto postsynaptic neurons, presynaptic circuits might offer the best target for attentional top-down influences. If those influences enabled presynaptic circuits to selectively entrain postsynaptic neurons, this might explain selective routing. Indeed, when two visual stimuli induce two gamma rhythms in V1, only the gamma induced by the attended stimulus entrains gamma in V4. Here, we modelled induced responses with a Dynamic Causal Model for Cross-Spectral Densities and found that selective entrainment can be explained by attentional modulation of intrinsic V1 connections. Specifically, local inhibition was decreased in the granular input layer and increased in the supragranular output layer of the V1 circuit that processed the attended stimulus. Thus, presynaptic attentional influences and ensuing entrainment were sufficient to mediate selective routing.

Accelerating scientific progress through Bayesian adversarial collaboration.

Adversarial collaboration has been championed as the gold standard for resolving scientific disputes but has gained relatively limited traction in neuroscience and allied fields. In this perspective, we argue that adversarial collaborative research has been stymied by an overly restrictive concern with the falsification of scientific theories. We advocate instead for a more expansive view that frames adversarial collaboration in terms of Bayesian belief updating, model comparison, and evidence accumulation. This framework broadens the scope of adversarial collaboration to accommodate a wide range of informative (but not necessarily definitive) studies while affording the requisite formal tools to guide experimental design and data analysis in the adversarial setting. We provide worked examples that demonstrate how these tools can be deployed to score theoretical models in terms of a common metric of evidence, thereby furnishing a means of tracking the amount of empirical support garnered by competing theories over time.

Self-regulation learning as active inference: dynamic causal modeling of an fMRI neurofeedback task.

Introduction: Learning to self-regulate brain activity by neurofeedback has been shown to lead to changes in the brain and behavior, with beneficial clinical and non-clinical outcomes. Neurofeedback uses a brain-computer interface to guide participants to change some feature of their brain activity. However, the neural mechanism of self-regulation learning remains unclear, with only 50% of the participants succeeding in achieving it. To bridge this knowledge gap, our study delves into the neural mechanisms of self-regulation learning via neurofeedback and investigates the brain processes associated with successful brain self-regulation. Methods: We study the neural underpinnings of self-regulation learning by employing dynamical causal modeling (DCM) in conjunction with real-time functional MRI data. The study involved a cohort of 18 participants undergoing neurofeedback training targeting the supplementary motor area. A critical focus was the comparison between top-down hierarchical connectivity models proposed by Active Inference and alternative bottom-up connectivity models like reinforcement learning. Results: Our analysis revealed a crucial distinction in brain connectivity patterns between successful and non-successful learners. Particularly, successful learners evinced a significantly stronger top-down effective connectivity towards the target area implicated in self-regulation. This heightened top-down network engagement closely resembles the patterns observed in goal-oriented and cognitive control studies, shedding light on the intricate cognitive processes intertwined with self-regulation learning. Discussion: The findings from our investigation underscore the significance of cognitive mechanisms in the process of self-regulation learning through neurofeedback. The observed stronger top-down effective connectivity in successful learners indicates the involvement of hierarchical cognitive control, which aligns with the tenets of Active Inference. This study contributes to a deeper understanding of the neural dynamics behind successful self-regulation learning and provides insights into the potential cognitive architecture underpinning this process.

An Active-Inference Approach to Second-Person Neuroscience.

Social neuroscience has often been criticized for approaching the investigation of the neural processes that enable social interaction and cognition from a passive, detached, third-person perspective, without involving any real-time social interaction. With the emergence of second-person neuroscience, investigators have uncovered the unique complexity of neural-activation patterns in actual, real-time interaction. Social cognition that occurs during social interaction is fundamentally different from that unfolding during social observation. However, it remains unclear how the neural correlates of social interaction are to be interpreted. Here, we leverage the active-inference framework to shed light on the mechanisms at play during social interaction in second-person neuroscience studies. Specifically, we show how counterfactually rich mutual predictions, real-time bodily adaptation, and policy selection explain activation in components of the default mode, salience, and frontoparietal networks of the brain, as well as in the basal ganglia. We further argue that these processes constitute the crucial neural processes that underwrite bona fide social interaction. By placing the experimental approach of second-person neuroscience on the theoretical foundation of the active-inference framework, we inform the field of social neuroscience about the mechanisms of real-life interactions. We thereby contribute to the theoretical foundations of empirical second-person neuroscience.

Experimental validation of the free-energy principle with in vitro neural networks.

Empirical applications of the free-energy principle are not straightforward because they entail a commitment to a particular process theory, especially at the cellular and synaptic levels. Using a recently established reverse engineering technique, we confirm the quantitative predictions of the free-energy principle using in vitro networks of rat cortical neurons that perform causal inference. Upon receiving electrical stimuli-generated by mixing two hidden sources-neurons self-organised to selectively encode the two sources. Pharmacological up- and downregulation of network excitability disrupted the ensuing inference, consistent with changes in prior beliefs about hidden sources. As predicted, changes in effective synaptic connectivity reduced variational free energy, where the connection strengths encoded parameters of the generative model. In short, we show that variational free energy minimisation can quantitatively predict the self-organisation of neuronal networks, in terms of their responses and plasticity. These results demonstrate the applicability of the free-energy principle to in vitro neural networks and establish its predictive validity in this setting.

Predictive coding and stochastic resonance as fundamental principles of auditory phantom perception.

Mechanistic insight is achieved only when experiments are employed to test formal or computational models. Furthermore, in analogy to lesion studies, phantom perception may serve as a vehicle to understand the fundamental processing principles underlying healthy auditory perception. With a special focus on tinnitus-as the prime example of auditory phantom perception-we review recent work at the intersection of artificial intelligence, psychology and neuroscience. In particular, we discuss why everyone with tinnitus suffers from (at least hidden) hearing loss, but not everyone with hearing loss suffers from tinnitus. We argue that intrinsic neural noise is generated and amplified along the auditory pathway as a compensatory mechanism to restore normal hearing based on adaptive stochastic resonance. The neural noise increase can then be misinterpreted as auditory input and perceived as tinnitus. This mechanism can be formalized in the Bayesian brain framework, where the percept (posterior) assimilates a prior prediction (brain's expectations) and likelihood (bottom-up neural signal). A higher mean and lower variance (i.e. enhanced precision) of the likelihood shifts the posterior, evincing a misinterpretation of sensory evidence, which may be further confounded by plastic changes in the brain that underwrite prior predictions. Hence, two fundamental processing principles provide the most explanatory power for the emergence of auditory phantom perceptions: predictive coding as a top-down and adaptive stochastic resonance as a complementary bottom-up mechanism. We conclude that both principles also play a crucial role in healthy auditory perception. Finally, in the context of neuroscience-inspired artificial intelligence, both processing principles may serve to improve contemporary machine learning techniques.

Neurochemistry-enriched dynamic causal models of magnetoencephalography, using magnetic resonance spectroscopy.

We present a hierarchical empirical Bayesian framework for testing hypotheses about neurotransmitters' concertation as empirical prior for synaptic physiology using ultra-high field magnetic resonance spectroscopy (7T-MRS) and magnetoencephalography data (MEG). A first level dynamic causal modelling of cortical microcircuits is used to infer the connectivity parameters of a generative model of individuals' neurophysiological observations. At the second level, individuals' 7T-MRS estimates of regional neurotransmitter concentration supply empirical priors on synaptic connectivity. We compare the group-wise evidence for alternative empirical priors, defined by monotonic functions of spectroscopic estimates, on subsets of synaptic connections. For efficiency and reproducibility, we used Bayesian model reduction (BMR), parametric empirical Bayes and variational Bayesian inversion. In particular, we used Bayesian model reduction to compare alternative model evidence of how spectroscopic neurotransmitter measures inform estimates of synaptic connectivity. This identifies the subset of synaptic connections that are influenced by individual differences in neurotransmitter levels, as measured by 7T-MRS. We demonstrate the method using resting-state MEG (i.e., task-free recording) and 7T-MRS data from healthy adults. Our results confirm the hypotheses that GABA concentration influences local recurrent inhibitory intrinsic connectivity in deep and superficial cortical layers, while glutamate influences the excitatory connections between superficial and deep layers and connections from superficial to inhibitory interneurons. Using within-subject split-sampling of the MEG dataset (i.e., validation by means of a held-out dataset), we show that model comparison for hypothesis testing can be highly reliable. The method is suitable for applications with magnetoencephalography or electroencephalography, and is well-suited to reveal the mechanisms of neurological and psychiatric disorders, including responses to psychopharmacological interventions.