Edge time series are increasingly used in brain imaging to study the node functional connectivity (nFC) dynamics at the finest temporal resolution while avoiding sliding windows. Here, we lay the ...mathematical foundations for the edge-centric analysis of neuroimaging time series, explaining why a few high-amplitude cofluctuations drive the nFC across datasets. Our exposition also constitutes a critique of the existing edge-centric studies, showing that their main findings can be derived from the nFC under a static null hypothesis that disregards temporal correlations. Testing the analytic predictions on functional MRI data from the Human Connectome Project confirms that the nFC can explain most variation in the edge FC matrix, the edge communities, the large cofluctuations, and the corresponding spatial patterns. We encourage the use of dynamic measures in future research, which exploit the temporal structure of the edge time series and cannot be replicated by static null models.
Neural information flow is inherently directional. To date, investigation of directional communication in the human structural connectome has been precluded by the inability of non-invasive ...neuroimaging methods to resolve axonal directionality. Here, we demonstrate that decentralized measures of network communication, applied to the undirected topology and geometry of brain networks, can infer putative directions of large-scale neural signalling. We propose the concept of send-receive communication asymmetry to characterize cortical regions as senders, receivers or neutral, based on differences between their incoming and outgoing communication efficiencies. Our results reveal a send-receive cortical hierarchy that recapitulates established organizational gradients differentiating sensory-motor and multimodal areas. We find that send-receive asymmetries are significantly associated with the directionality of effective connectivity derived from spectral dynamic causal modeling. Finally, using fruit fly, mouse and macaque connectomes, we provide further evidence suggesting that directionality of neural signalling is significantly encoded in the undirected architecture of nervous systems.
Recently, there has been a lot of interest in characterising the connectivity of resting state brain networks. Most of the literature uses functional connectivity to examine these intrinsic brain ...networks. Functional connectivity has well documented limitations because of its inherent inability to identify causal interactions. Dynamic causal modelling (DCM) is a framework that allows for the identification of the causal (directed) connections among neuronal systems — known as effective connectivity. This technical note addresses the validity of a recently proposed DCM for resting state fMRI – as measured in terms of their complex cross spectral density – referred to as spectral DCM. Spectral DCM differs from (the alternative) stochastic DCM by parameterising neuronal fluctuations using scale free (i.e., power law) forms, rendering the stochastic model of neuronal activity deterministic. Spectral DCM not only furnishes an efficient estimation of model parameters but also enables the detection of group differences in effective connectivity, the form and amplitude of the neuronal fluctuations or both. We compare and contrast spectral and stochastic DCM models with endogenous fluctuations or state noise on hidden states. We used simulated data to first establish the face validity of both schemes and show that they can recover the model (and its parameters) that generated the data. We then used Monte Carlo simulations to assess the accuracy of both schemes in terms of their root mean square error. We also simulated group differences and compared the ability of spectral and stochastic DCMs to identify these differences. We show that spectral DCM was not only more accurate but also more sensitive to group differences. Finally, we performed a comparative evaluation using real resting state fMRI data (from an open access resource) to study the functional integration within default mode network using spectral and stochastic DCMs.
•This paper provides construct validation of spectral DCM against stochastic DCM.•Spectral DCM is shown to be more accurate than stochastic DCM in terms of root mean square error.•Spectral DCM is shown to be more sensitive at identifying group differences.
Integrating neurons into digital systems may enable performance infeasible with silicon alone. Here, we develop DishBrain, a system that harnesses the inherent adaptive computation of neurons in a ...structured environment. In vitro neural networks from human or rodent origins are integrated with in silico computing via a high-density multielectrode array. Through electrophysiological stimulation and recording, cultures are embedded in a simulated game-world, mimicking the arcade game “Pong.” Applying implications from the theory of active inference via the free energy principle, we find apparent learning within five minutes of real-time gameplay not observed in control conditions. Further experiments demonstrate the importance of closed-loop structured feedback in eliciting learning over time. Cultures display the ability to self-organize activity in a goal-directed manner in response to sparse sensory information about the consequences of their actions, which we term synthetic biological intelligence. Future applications may provide further insights into the cellular correlates of intelligence.
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•Improvements in performance or “learning” over time following closed-loop feedback•Learning observed from both human and primary mouse cortical neurons•Systems with stimulus but no feedback show no learning•Dynamic changes observed in neural electrophysiological activity during embodiment
The DishBrain system is the first real-time synthetic biological intelligence platform that demonstrates that biological neurons can adjust firing activity in a way that suggests the ability to learn to perform goal-oriented tasks when provided with simple electrophysiological sensory input and feedback while embodied in a game-world.
Abstract
An important characteristic of spontaneous brain activity is the anticorrelation between the core default network (cDN) and the dorsal attention network (DAN) and the salience network (SN). ...This anticorrelation may constitute a key aspect of functional anatomy and is implicated in several brain disorders. We used dynamic causal modeling to assess the hypothesis that a causal hierarchy underlies this anticorrelation structure, using resting-state fMRI of healthy adolescent and young adults (N = 404). Our analysis revealed an asymmetric effective connectivity, such that the regions in the SN and DAN exerted an inhibitory influence on the cDN regions; whereas the cDN exerted an excitatory influence on the SN and DAN regions. The relative strength of efferent versus afferent connections places the SN at the apex of the hierarchy, suggesting that the SN modulates anticorrelated networks with descending hierarchical connections. In short, this study of directed neuronal coupling reveals a causal hierarchical architecture that generates or orchestrates anticorrelation of brain activity. These new findings shed light on functional integration of intrinsic brain networks at rest and speak to future dynamic causal modeling studies of large-scale networks.
Context-sensitive and activity-dependent fluctuations in connectivity underlie functional integration in the brain and have been studied widely in terms of synaptic plasticity, learning and ...condition-specific (e.g., attentional) modulations of synaptic efficacy. This dynamic aspect of brain connectivity has recently attracted a lot of attention in the resting state fMRI community. To explain dynamic functional connectivity in terms of directed effective connectivity among brain regions, we introduce a novel method to identify dynamic effective connectivity using spectral dynamic causal modelling (spDCM). We used parametric empirical Bayes (PEB) to model fluctuations in directed coupling over consecutive windows of resting state fMRI time series. Hierarchical PEB can model random effects on connectivity parameters at the second (between-window) level given connectivity estimates from the first (within-window) level. In this work, we used a discrete cosine transform basis set or eigenvariates (i.e., expression of principal components) to model fluctuations in effective connectivity over windows. We evaluated the ensuing dynamic effective connectivity in terms of the consistency of baseline connectivity within default mode network (DMN), using the resting state fMRI from Human Connectome Project (HCP). To model group-level baseline and dynamic effective connectivity for DMN, we extended the PEB approach by conducting a multilevel PEB analysis of between-session and between-subject group effects. Model comparison clearly spoke to dynamic fluctuations in effective connectivity – and the dynamic functional connectivity these changes explain. Furthermore, baseline effective connectivity was consistent across independent sessions – and notably more consistent than estimates based upon conventional models. This work illustrates the advantage of hierarchical modelling with spDCM, in characterizing the dynamics of effective connectivity.
•We describe efficient estimation of dynamics in resting state effective connectivity.•Spectral DCM and PEB are used to model fluctuations in neuronal coupling over time.•Dynamics in responses are explained in terms of its causes (effective connectivity).•Baseline and dynamic components of the default mode connectivity are identified.
Abstract
This technical report describes the dynamic causal modelling of mitigated epidemiological outcomes during the COVID-9 coronavirus outbreak in 2020. Dynamic causal modelling is a form of ...complex system modelling, which uses ‘real world’ timeseries to estimate the parameters of an underlying state space model using variational Bayesian procedures. Its key contribution—in an epidemiological setting—is to embed conventional models within a larger model of sociobehavioural responses—in a way that allows for (relatively assumption-free) forecasting. One advantage of using variational Bayes is that one can progressively optimise the model via Bayesian model selection: generally, the most likely models become more expressive as more data becomes available. This report summarises the model (on 6-Nov-20), eight months after the inception of dynamic causal modelling for COVID-19. This model—and its subsequent updates—is used to provide nowcasts and forecasts of latent behavioural and epidemiological variables as an open science resource. The current report describes the underlying model structure and the rationale for the variational procedures that underwrite Bayesian model selection.
The rostral anterior cingulate cortex (rACC) is consistently implicated in the neurobiology of depression. While the functional connectivity of the rACC has been previously associated with treatment ...response, there is a paucity of work investigating the specific directional interactions underpinning these associations. We compared the fMRI resting-state effective connectivity of 94 young people with major depressive disorder and 91 healthy controls. Following the fMRI scan, patients were randomized to receive cognitive behavioral therapy for 12 weeks, plus either fluoxetine or a placebo. Using spectral dynamic causal modelling, we examined the effective connectivity of the rACC with eight other regions implicated in depression: the left and right anterior insular cortex (AIC), amygdalae, and dorsolateral prefrontal cortex (dlPFC); and in the midline, the subgenual (sgACC) and dorsal anterior cingulate cortex (dACC). Parametric empirical Bayes was used to compare baseline differences between controls and patients and responders and non-responders to treatment. Depressed patients demonstrated greater inhibitory connectivity from the rACC to the dlPFC, AIC, dACC and left amygdala. Moreover, treatment responders illustrated greater inhibitory connectivity from the rACC to dACC, greater excitatory connectivity from the dACC to sgACC and reduced inhibitory connectivity from the sgACC to amygdalae at baseline. The inhibitory hyperconnectivity of the rACC in depressed patients aligns with hypotheses concerning the dominance of the default mode network over other intrinsic brain networks. Surprisingly, treatment responders did not demonstrate connectivity which was more similar to healthy controls, but rather distinct alterations that may have predicated their enhanced treatment response.
The maintenance of wellbeing across the lifespan depends on the preservation of cognitive function. We propose that successful cognitive aging is determined by interactions both within and between ...large-scale functional brain networks. Such connectivity can be estimated from task-free functional magnetic resonance imaging (fMRI), also known as resting-state fMRI (rs-fMRI). However, common correlational methods are confounded by age-related changes in the neurovascular signaling. To estimate network interactions at the neuronal rather than vascular level, we used generative models that specified both the neural interactions and a flexible neurovascular forward model. The networks' parameters were optimized to explain the spectral dynamics of rs-fMRI data in 602 healthy human adults from population-based cohorts who were approximately uniformly distributed between 18 and 88 years (www.cam-can.com). We assessed directed connectivity within and between three key large-scale networks: the salience network, dorsal attention network, and default mode network. We found that age influences connectivity both within and between these networks, over and above the effects on neurovascular coupling. Canonical correlation analysis revealed that the relationship between network connectivity and cognitive function was age-dependent: cognitive performance relied on neural dynamics more strongly in older adults. These effects were driven partly by reduced stability of neural activity within all networks, as expressed by an accelerated decay of neural information. Our findings suggest that the balance of excitatory connectivity between networks, and the stability of intrinsic neural representations within networks, changes with age. The cognitive function of older adults becomes increasingly dependent on these factors.
Maintaining cognitive function is critical to successful aging. To study the neural basis of cognitive function across the lifespan, we studied a large population-based cohort (n = 602, 18-88 years), separating neural connectivity from vascular components of fMRI signals. Cognitive ability was influenced by the strength of connection within and between functional brain networks, and this positive relationship increased with age. In older adults, there was more rapid decay of intrinsic neuronal activity in multiple regions of the brain networks, which related to cognitive performance. Our data demonstrate increased reliance on network flexibility to maintain cognitive function, in the presence of more rapid decay of neural activity. These insights will facilitate the development of new strategies to maintain cognitive ability.
Given the rapid advancement of artificial intelligence, understanding the foundations of intelligent behaviour is increasingly important. Active inference, regarded as a general theory of behaviour, ...offers a principled approach to probing the basis of sophistication in planning and decision-making. This paper examines two decision-making schemes in active inference based on “planning” and “learning from experience”. Furthermore, we also introduce a mixed model that navigates the data complexity trade-off between these strategies, leveraging the strengths of both to facilitate balanced decision-making. We evaluate our proposed model in a challenging grid-world scenario that requires adaptability from the agent. Additionally, our model provides the opportunity to analyse the evolution of various parameters, offering valuable insights and contributing to an explainable framework for intelligent decision-making.
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