Music in the brain.

Music is ubiquitous across human cultures - as a source of affective and pleasurable experience, moving us both physically and emotionally - and learning to play music shapes both brain structure and brain function. Music processing in the brain - namely, the perception of melody, harmony and rhythm - has traditionally been studied as an auditory phenomenon using passive listening paradigms. However, when listening to music, we actively generate predictions about what is likely to happen next. This enactive aspect has led to a more comprehensive understanding of music processing involving brain structures implicated in action, emotion and learning. Here we review the cognitive neuroscience literature of music perception. We show that music perception, action, emotion and learning all rest on the human brain's fundamental capacity for prediction - as formulated by the predictive coding of music model. This Review elucidates how this formulation of music perception and expertise in individuals can be extended to account for the dynamics and underlying brain mechanisms of collective music making. This in turn has important implications for human creativity as evinced by music improvisation. These recent advances shed new light on what makes music meaningful from a neuroscientific perspective.

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).

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.

Neural Mechanisms and Psychology of Psychedelic Ego Dissolution.

Neuroimaging studies of psychedelics have advanced our understanding of hierarchical brain organization and the mechanisms underlying their subjective and therapeutic effects. The primary mechanism of action of classic psychedelics is binding to serotonergic 5-HT2A receptors. Agonist activity at these receptors leads to neuromodulatory changes in synaptic efficacy that can have a profound effect on hierarchical message-passing in the brain. Here, we review the cognitive and neuroimaging evidence for the effects of psychedelics: in particular, their influence on selfhood and subject-object boundaries-known as ego dissolution-surmised to underwrite their subjective and therapeutic effects. Agonism of 5-HT2A receptors, located at the apex of the cortical hierarchy, may have a particularly powerful effect on sentience and consciousness. These effects can endure well after the pharmacological half-life, suggesting that psychedelics may have effects on neural plasticity that may play a role in their therapeutic efficacy. Psychologically, this may be accompanied by a disarming of ego resistance that increases the repertoire of perceptual hypotheses and affords alternate pathways for thought and behavior, including those that undergird selfhood. We consider the interaction between serotonergic neuromodulation and sentience through the lens of hierarchical predictive coding, which speaks to the value of psychedelics in understanding how we make sense of the world and specific predictions about effective connectivity in cortical hierarchies that can be tested using functional neuroimaging. SIGNIFICANCE STATEMENT: Classic psychedelics bind to serotonergic 5-HT2A receptors. Their agonist activity at these receptors leads to neuromodulatory changes in synaptic efficacy, resulting in a profound effect on information processing in the brain. Here, we synthesize an abundance of brain imaging research with pharmacological and psychological interpretations informed by the framework of predictive coding. Moreover, predictive coding is suggested to offer more sophisticated interpretations of neuroimaging findings by bridging the role between the 5-HT2A receptors and large-scale brain networks.

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.

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.

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.

Neurophysiological consequences of synapse loss in progressive supranuclear palsy.

Synaptic loss occurs early in many neurodegenerative diseases and contributes to cognitive impairment even in the absence of gross atrophy. Currently, for human disease there are few formal models to explain how cortical networks underlying cognition are affected by synaptic loss. We advocate that biophysical models of neurophysiology offer both a bridge from preclinical to clinical models of pathology and quantitative assays for experimental medicine. Such biophysical models can also disclose hidden neuronal dynamics generating neurophysiological observations such as EEG and magnetoencephalography. Here, we augment a biophysically informed mesoscale model of human cortical function by inclusion of synaptic density estimates as captured by 11C-UCB-J PET, and provide insights into how regional synapse loss affects neurophysiology. We use the primary tauopathy of progressive supranuclear palsy (Richardson's syndrome) as an exemplar condition, with high clinicopathological correlations. Progressive supranuclear palsy causes a marked change in cortical neurophysiology in the presence of mild cortical atrophy and is associated with a decline in cognitive functions associated with the frontal lobe. Using parametric empirical Bayesian inversion of a conductance-based canonical microcircuit model of magnetoencephalography data, we show that the inclusion of regional synaptic density-as a subject-specific prior on laminar-specific neuronal populations-markedly increases model evidence. Specifically, model comparison suggests that a reduction in synaptic density in inferior frontal cortex affects superficial and granular layer glutamatergic excitation. This predicted individual differences in behaviour, demonstrating the link between synaptic loss, neurophysiology and cognitive deficits. The method we demonstrate is not restricted to progressive supranuclear palsy or the effects of synaptic loss: such pathology-enriched dynamic causal models can be used to assess the mechanisms of other neurological disorders, with diverse non-invasive measures of pathology, and is suitable to test the effects of experimental pharmacology.

Altered effective connectivity in sensorimotor cortices is a signature of severity and clinical course in depression.

Functional neuroimaging research on depression has traditionally targeted neural networks associated with the psychological aspects of depression. In this study, instead, we focus on alterations of sensorimotor function in depression. We used resting-state functional MRI data and dynamic causal modeling (DCM) to assess the hypothesis that depression is associated with aberrant effective connectivity within and between key regions in the sensorimotor hierarchy. Using hierarchical modeling of between-subject effects in DCM with parametric empirical Bayes we first established the architecture of effective connectivity in sensorimotor cortices. We found that in (interoceptive and exteroceptive) sensory cortices across participants, the backward connections are predominantly inhibitory, whereas the forward connections are mainly excitatory in nature. In motor cortices these parities were reversed. With increasing depression severity, these patterns are depreciated in exteroceptive and motor cortices and augmented in the interoceptive cortex, an observation that speaks to depressive symptomatology. We established the robustness of these results in a leave-one-out cross-validation analysis and by reproducing the main results in a follow-up dataset. Interestingly, with (nonpharmacological) treatment, depression-associated changes in backward and forward effective connectivity partially reverted to group mean levels. Overall, altered effective connectivity in sensorimotor cortices emerges as a promising and quantifiable candidate marker of depression severity and treatment response.

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.

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.

In the Body's Eye: The computational anatomy of interoceptive inference.

A growing body of evidence highlights the intricate linkage of exteroceptive perception to the rhythmic activity of the visceral body. In parallel, interoceptive inference theories of affective perception and self-consciousness are on the rise in cognitive science. However, thus far no formal theory has emerged to integrate these twin domains; instead, most extant work is conceptual in nature. Here, we introduce a formal model of cardiac active inference, which explains how ascending cardiac signals entrain exteroceptive sensory perception and uncertainty. Through simulated psychophysics, we reproduce the defensive startle reflex and commonly reported effects linking the cardiac cycle to affective behaviour. We further show that simulated 'interoceptive lesions' blunt affective expectations, induce psychosomatic hallucinations, and exacerbate biases in perceptual uncertainty. Through synthetic heart-rate variability analyses, we illustrate how the balance of arousal-priors and visceral prediction errors produces idiosyncratic patterns of physiological reactivity. Our model thus offers a roadmap for computationally phenotyping disordered brain-body interaction.

Bayesian data assimilation for estimating instantaneous reproduction numbers during epidemics: Applications to COVID-19.

Estimating the changes of epidemiological parameters, such as instantaneous reproduction number, Rt, is important for understanding the transmission dynamics of infectious diseases. Current estimates of time-varying epidemiological parameters often face problems such as lagging observations, averaging inference, and improper quantification of uncertainties. To address these problems, we propose a Bayesian data assimilation framework for time-varying parameter estimation. Specifically, this framework is applied to estimate the instantaneous reproduction number Rt during emerging epidemics, resulting in the state-of-the-art 'DARt' system. With DARt, time misalignment caused by lagging observations is tackled by incorporating observation delays into the joint inference of infections and Rt; the drawback of averaging is overcome by instantaneously updating upon new observations and developing a model selection mechanism that captures abrupt changes; the uncertainty is quantified and reduced by employing Bayesian smoothing. We validate the performance of DARt and demonstrate its power in describing the transmission dynamics of COVID-19. The proposed approach provides a promising solution for making accurate and timely estimation for transmission dynamics based on reported data.

Aberrant temporal-spatial complexity of intrinsic fluctuations in major depression.

Accumulating evidence suggests that the brain is highly dynamic; thus, investigation of brain dynamics especially in brain connectivity would provide crucial information that stationary functional connectivity could miss. This study investigated temporal expressions of spatial modes within the default mode network (DMN), salience network (SN) and cognitive control network (CCN) using a reliable data-driven co-activation pattern (CAP) analysis in two independent data sets. We found enhanced CAP-to-CAP transitions of the SN in patients with MDD. Results suggested enhanced flexibility of this network in the patients. By contrast, we also found reduced spatial consistency and persistence of the DMN in the patients, indicating reduced variability and stability in individuals with MDD. In addition, the patients were characterized by prominent activation of mPFC. Moreover, further correlation analysis revealed that persistence and transitions of RCCN were associated with the severity of depression. Our findings suggest that functional connectivity in the patients may not be simply attenuated or potentiated, but just alternating faster or slower among more complex patterns. The aberrant temporal-spatial complexity of intrinsic fluctuations reflects functional diaschisis of resting-state networks as characteristic of patients with MDD.

Brain circuits signaling the absence of emotion in body language.

Adaptive social behavior and mental well-being depend on not only recognizing emotional expressions but also, inferring the absence of emotion. While the neurobiology underwriting the perception of emotions is well studied, the mechanisms for detecting a lack of emotional content in social signals remain largely unknown. Here, using cutting-edge analyses of effective brain connectivity, we uncover the brain networks differentiating neutral and emotional body language. The data indicate greater activation of the right amygdala and midline cerebellar vermis to nonemotional as opposed to emotional body language. Most important, the effective connectivity between the amygdala and insula predicts people's ability to recognize the absence of emotion. These conclusions extend substantially current concepts of emotion perception by suggesting engagement of limbic effective connectivity in recognizing the lack of emotion in body language reading. Furthermore, the outcome may advance the understanding of overly emotional interpretation of social signals in depression or schizophrenia by providing the missing link between body language reading and limbic pathways. The study thus opens an avenue for multidisciplinary research on social cognition and the underlying cerebrocerebellar networks, ranging from animal models to patients with neuropsychiatric conditions.

Estimating anisotropy directly via neural timeseries.

An isotropic dynamical system is one that looks the same in every direction, i.e., if we imagine standing somewhere within an isotropic system, we would not be able to differentiate between different lines of sight. Conversely, anisotropy is a measure of the extent to which a system deviates from perfect isotropy, with larger values indicating greater discrepancies between the structure of the system along its axes. Here, we derive the form of a generalised scalable (mechanically similar) discretized field theoretic Lagrangian that allows for levels of anisotropy to be directly estimated via timeseries of arbitrary dimensionality. We generate synthetic data for both isotropic and anisotropic systems and, by using Bayesian model inversion and reduction, show that we can discriminate between the two datasets - thereby demonstrating proof of principle. We then apply this methodology to murine calcium imaging data collected in rest and task states, showing that anisotropy can be estimated directly from different brain states and cortical regions in an empirical in vivo biological setting. We hope that this theoretical foundation, together with the methodology and publicly available MATLAB code, will provide an accessible way for researchers to obtain new insight into the structural organization of neural systems in terms of how scalable neural regions grow - both ontogenetically during the development of an individual organism, as well as phylogenetically across species.

Waves of prediction.

Predictive processing (e.g., predictive coding) is a predominant paradigm in cognitive neuroscience. This Primer considers the various levels of commitment neuroscientists have to the neuronal process theories that accompany the principles of predictive processing. Specifically, it reviews and contextualises a recent PLOS Biology study of alpha oscillations and travelling waves. We will see that alpha oscillations emerge naturally under the computational architectures implied by predictive coding-and may tell us something profound about recurrent message passing in brain hierarchies. Specifically, the bidirectional nature of forward and backward waves speaks to opportunities to understand attention and how it nuances bottom-up and top-down influences.

Entorhinal transformations in abstract frames of reference.

Knowing how another's preferences relate to our own is a central aspect of everyday decision-making, yet how the brain performs this transformation is unclear. Here, we ask whether the putative role of the hippocampal-entorhinal system in transforming relative and absolute spatial coordinates during navigation extends to transformations in abstract decision spaces. During functional magnetic resonance imaging (fMRI), subjects learned a stranger's preference for an everyday activity-relative to one of three personally known individuals-and subsequently decided how the stranger's preference relates to the other two individuals' preferences. We observed entorhinal/subicular responses to the absolute distance between the ratings of the stranger and the familiar choice options. Notably, entorhinal/subicular signals were sensitive to which familiar individuals were being compared to the stranger. In contrast, striatal signals increased when accurately determining the ordinal position of choice options in relation to the stranger. Paralleling its role in navigation, these data implicate the entorhinal/subicular region in assimilating relatively coded knowledge within abstract metric spaces.

Difficulties with Speech-in-Noise Perception Related to Fundamental Grouping Processes in Auditory Cortex.

In our everyday lives, we are often required to follow a conversation when background noise is present ("speech-in-noise" [SPIN] perception). SPIN perception varies widely-and people who are worse at SPIN perception are also worse at fundamental auditory grouping, as assessed by figure-ground tasks. Here, we examined the cortical processes that link difficulties with SPIN perception to difficulties with figure-ground perception using functional magnetic resonance imaging. We found strong evidence that the earliest stages of the auditory cortical hierarchy (left core and belt areas) are similarly disinhibited when SPIN and figure-ground tasks are more difficult (i.e., at target-to-masker ratios corresponding to 60% rather than 90% performance)-consistent with increased cortical gain at lower levels of the auditory hierarchy. Overall, our results reveal a common neural substrate for these basic (figure-ground) and naturally relevant (SPIN) tasks-which provides a common computational basis for the link between SPIN perception and fundamental auditory grouping.