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There is consensus that activation within distributed functional brain networks underlies human thought. The impact of this consensus is limited, however, by a gap that exists between data-driven correlational analyses that specify where functional brain activity is localized using functional magnetic resonance imaging (fMRI), and neural process accounts that specify how neural activity unfolds through time to give rise to behavior. Here, we show how an integrative cognitive neuroscience approach may bridge this gap. In an exemplary study of visual working memory, we use multilevel Bayesian statistics to demonstrate that a neural dynamic model simultaneously explains behavioral data and predicts localized patterns of brain activity, outperforming standard analytic approaches to fMRI. The model explains performance on both correct trials and incorrect trials where errors in change detection emerge from neural fluctuations amplified by neural interaction. Critically, predictions of the model run counter to cognitive theories of the origin of errors in change detection. Results reveal neural patterns predicted by the model within regions of the dorsal attention network that have been the focus of much debate. The model-based analysis suggests that key areas in the dorsal attention network such as the intraparietal sulcus play a central role in change detection rather than working memory maintenance, counter to previous interpretations of fMRI studies. More generally, the integrative cognitive neuroscience approach used here establishes a framework for directly testing theories of cognitive and brain function using the combined power of behavioral and fMRI data. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

We introduce a probabilistic (Bayesian) framework and associated software toolbox for mapping population receptive fields (pRFs) based on fMRI data. This generic approach is intended to work with stimuli of any dimension and is demonstrated and validated in the context of 2D retinotopic mapping. The framework enables the experimenter to specify generative (encoding) models of fMRI timeseries, in which experimental stimuli enter a pRF model of neural activity, which in turns drives a nonlinear model of neurovascular coupling and Blood Oxygenation Level Dependent (BOLD) response. The neuronal and haemodynamic parameters are estimated together on a voxel-by-voxel or region-of-interest basis using a Bayesian estimation algorithm (variational Laplace). This offers several novel contributions to receptive field modelling. The variance/covariance of parameters are estimated, enabling receptive fields to be plotted while properly representing uncertainty about pRF size and location. Variability in the haemodynamic response across the brain is accounted for. Furthermore, the framework introduces formal hypothesis testing to pRF analysis, enabling competing models to be evaluated based on their log model evidence (approximated by the variational free energy), which represents the optimal tradeoff between accuracy and complexity. Using simulations and empirical data, we found that parameters typically used to represent pRF size and neuronal scaling are strongly correlated, which is taken into account by the Bayesian methods we describe when making inferences. We used the framework to compare the evidence for six variants of pRF model using 7 T functional MRI data and we found a circular Difference of Gaussians (DoG) model to be the best explanation for our data overall. We hope this framework will prove useful for mapping stimulus spaces with any number of dimensions onto the anatomy of the brain., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Here we introduce a multivariate framework for characterising longitudinal changes in structural MRI using dynamical systems. The general approach enables modelling changes of states in multiple imaging biomarkers typically observed during brain development, plasticity, ageing and degeneration, e.g. regional gray matter volume of multiple regions of interest (ROIs). Structural brain states follow intrinsic dynamics according to a linear system with additional inputs accounting for potential driving forces of brain development. In particular, the inputs to the system are specified to account for known or latent developmental growth/decline factors, e.g. due to effects of growth hormones, puberty, or sudden behavioural changes etc. Because effects of developmental factors might be region-specific, the sensitivity of each ROI to contributions of each factor is explicitly modelled. In addition to the external effects of developmental factors on regional change, the framework enables modelling and inference about directed (potentially reciprocal) interactions between brain regions, due to competition for space, or structural connectivity, and suchlike. This approach accounts for repeated measures in typical MRI studies of development and aging. Model inversion and posterior distributions are obtained using earlier established variational methods enabling Bayesian evidence-based comparisons between various models of structural change. Using this approach we demonstrate dynamic cortical changes during brain maturation between 6 and 22 years of age using a large openly available longitudinal paediatric dataset with 637 scans from 289 individuals. In particular, we model volumetric changes in 26 bilateral ROIs, which cover large portions of cortical and subcortical gray matter. We account for (1) puberty-related effects on gray matter regions; (2) effects of an early transient growth process with additional time-lag parameter; (3) sexual dimorphism by modelling parameter differences between boys and girls. There is evidence that the regional pattern of sensitivity to dynamic hidden growth factors in late childhood is similar across genders and shows a consistent anterior-posterior gradient with strongest impact to prefrontal cortex (PFC) brain changes. Finally, we demonstrate the potential of the framework to explore the coupling of structural changes across a priori defined subnetworks using an example of previously established resting state functional connectivity., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Neural Mass Models provide a compact description of the dynamical activity of cell populations in neocortical regions. Moreover, models of regional activity can be connected together into networks, and inferences made about the strength of connections, using M/EEG data and Bayesian inference. To date, however, Bayesian methods have been largely restricted to the Variational Laplace (VL) algorithm which assumes that the posterior distribution is Gaussian and finds model parameters that are only locally optimal. This paper explores the use of Annealed Importance Sampling (AIS) to address these restrictions. We implement AIS using proposals derived from Langevin Monte Carlo (LMC) which uses local gradient and curvature information for efficient exploration of parameter space. In terms of the estimation of Bayes factors, VL and AIS agree about which model is best but report different degrees of belief. Additionally, AIS finds better model parameters and we find evidence of non-Gaussianity in their posterior distribution.

In this technical note we compare the performance of four gradient-free MCMC samplers (random walk Metropolis sampling, slice-sampling, adaptive MCMC sampling and population-based MCMC sampling with tempering) in terms of the number of independent samples they can produce per unit computational time. For the Bayesian inversion of a single-node neural mass model, both adaptive and population-based samplers are more efficient compared with random walk Metropolis sampler or slice-sampling; yet adaptive MCMC sampling is more promising in terms of compute time. Slice-sampling yields the highest number of independent samples from the target density - albeit at almost 1000% increase in computational time, in comparison to the most efficient algorithm (i.e., the adaptive MCMC sampler)., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

This paper is about the fitting or inversion of dynamic causal models (DCMs) of fMRI time series. It tries to establish the validity of stochastic DCMs that accommodate random fluctuations in hidden neuronal and physiological states. We compare and contrast deterministic and stochastic DCMs, which do and do not ignore random fluctuations or noise on hidden states. We then compare stochastic DCMs, which do and do not ignore conditional dependence between hidden states and model parameters (generalised filtering and dynamic expectation maximisation, respectively). We first characterise state-noise by comparing the log evidence of models with different a priori assumptions about its amplitude, form and smoothness. Face validity of the inversion scheme is then established using data simulated with and without state-noise to ensure that DCM can identify the parameters and model that generated the data. Finally, we address construct validity using real data from an fMRI study of internet addiction. Our analyses suggest the following. (i) The inversion of stochastic causal models is feasible, given typical fMRI data. (ii) State-noise has nontrivial amplitude and smoothness. (iii) Stochastic DCM has face validity, in the sense that Bayesian model comparison can distinguish between data that have been generated with high and low levels of physiological noise and model inversion provides veridical estimates of effective connectivity. (iv) Relaxing conditional independence assumptions can have greater construct validity, in terms of revealing group differences not disclosed by variational schemes. Finally, we note that the ability to model endogenous or random fluctuations on hidden neuronal (and physiological) states provides a new and possibly more plausible perspective on how regionally specific signals in fMRI are generated., (Copyright © 2011. Published by Elsevier Inc.)

Functional magnetic resonance imaging (fMRI), with blood oxygenation level-dependent (BOLD) contrast, is a widely used technique for studying the human brain. However, it is an indirect measure of underlying neuronal activity and the processes that link this activity to BOLD signals are still a topic of much debate. In order to relate findings from fMRI research to other measures of neuronal activity it is vital to understand the underlying neurovascular coupling mechanism. Currently, there is no consensus on the relative roles of synaptic and spiking activity in the generation of the BOLD response. Here we designed a modelling framework to investigate different neurovascular coupling mechanisms. We use Electroencephalographic (EEG) and fMRI data from a visual stimulation task together with biophysically informed mathematical models describing how neuronal activity generates the BOLD signals. These models allow us to non-invasively infer the degree of local synaptic and spiking activity in the healthy human brain. In addition, we use Bayesian model comparison to decide between neurovascular coupling mechanisms. We show that the BOLD signal is dependent upon both the synaptic and spiking activity but that the relative contributions of these two inputs are dependent upon the underlying neuronal firing rate. When the underlying neuronal firing is low then the BOLD response is best explained by synaptic activity. However, when the neuronal firing rate is high then both synaptic and spiking activity are required to explain the BOLD signal.

Mathematical models of scientific data can be formally compared using Bayesian model evidence. Previous applications in the biological sciences have mainly focussed on model selection in which one first selects the model with the highest evidence and then makes inferences based on the parameters of that model. This "best model" approach is very useful but can become brittle if there are a large number of models to compare, and if different subjects use different models. To overcome this shortcoming we propose the combination of two further approaches: (i) family level inference and (ii) Bayesian model averaging within families. Family level inference removes uncertainty about aspects of model structure other than the characteristic of interest. For example: What are the inputs to the system? Is processing serial or parallel? Is it linear or nonlinear? Is it mediated by a single, crucial connection? We apply Bayesian model averaging within families to provide inferences about parameters that are independent of further assumptions about model structure. We illustrate the methods using Dynamic Causal Models of brain imaging data.

In previous work (Penny et al., [2005]: Neuroimage 24:350-362) we have developed a spatially regularised General Linear Model for the analysis of functional magnetic resonance imaging data that allows for the characterisation of regionally specific effects using Posterior Probability Maps (PPMs). In this paper we show how it also provides an approximation to the model evidence. This is important as it is the basis of Bayesian model comparison and provides a unified framework for Bayesian Analysis of Variance, Cluster of Interest analyses and the principled selection of signal and noise models. We also provide extensions that implement spatial and anatomical regularisation of noise process parameters., ((c) 2006 Wiley-Liss, Inc.)

The mechanisms underlying interhemispheric integration (IHI) remain poorly understood, particularly for lateralized cognitive processes. To test competing theories of IHI, we constructed and fitted dynamic causal models to functional magnetic resonance data from two visual tasks that operated on identical stimuli but showed opposite hemispheric dominance. Using a systematic Bayesian model selection procedure, we found that, in the ventral visual stream, which was activated by letter judgments, interhemispheric connections mediated asymmetric information transfer from the nonspecialized right to the specialized left hemisphere when the latter did not have direct access to stimulus information. Notably, this form of IHI did not engage all areas activated by the task but was specific for areas in the lingual and fusiform gyri. In the dorsal stream, activated by spatial judgments, it did not matter which hemisphere received the stimulus: interhemispheric coupling increased bidirectionally, reflecting recruitment of the nonspecialized left hemisphere. Again, not all areas activated by the task were involved in this form of IHI; instead, it was restricted to interactions between areas in the superior parietal gyrus. Overall, our results provide direct neurophysiological evidence, in terms of effective connectivity, for the existence of context-dependent mechanisms of IHI that are implemented by specific visual areas during task-driven lateralization.

Complex processes resulting from interaction of multiple elements can rarely be understood by analytical scientific approaches alone; additional, mathematical models of system dynamics are required. This insight, which disciplines like physics have embraced for a long time already, is gradually gaining importance in the study of cognitive processes by functional neuroimaging. In this field, causal mechanisms in neural systems are described in terms of effective connectivity. Recently, dynamic causal modelling (DCM) was introduced as a generic method to estimate effective connectivity from neuroimaging data in a Bayesian fashion. One of the key advantages of DCM over previous methods is that it distinguishes between neural state equations and modality-specific forward models that translate neural activity into a measured signal. Another strength is its natural relation to Bayesian model selection (BMS) procedures. In this article, we review the conceptual and mathematical basis of DCM and its implementation for functional magnetic resonance imaging data and event-related potentials. After introducing the application of BMS in the context of DCM, we conclude with an outlook to future extensions of DCM. These extensions are guided by the long-term goal of using dynamic system models for pharmacological and clinical applications, particularly with regard to synaptic plasticity.

The cognitive and neural mechanisms mediating category-selective responses in the human brain remain controversial. Using functional magnetic resonance imaging and effective connectivity analyses (Dynamic Causal Modelling), we investigated animal- and tool-selective responses by manipulating stimulus modality (pictures versus words) and task (implicit versus explicit semantic). We dissociated two distinct mechanisms that engender category selectivity: in the ventral occipito-temporal cortex, tool-selective responses were observed irrespective of task, greater for pictures and mediated by bottom-up effects. In a left temporo-parietal action system, tool-selective responses were observed irrespective of modality, greater for explicit semantic tasks and mediated by top-down modulation from the left prefrontal cortex. These distinct activation and connectivity patterns suggest that the two systems support different cognitive operations, with the ventral occipito-temporal regions engaged in structural processing and the dorsal visuo-motor system in strategic semantic processing. Consistent with current semantic theories, explicit semantic processing of tools might thus rely on reactivating their associated action representations via top-down modulation. In terms of neuronal mechanisms, the category selectivity may be mediated by distinct top-down (task-dependent) and bottom-up (stimulus-dependent) mechanisms.

The anatomy of the corpus callosum has been described in considerable detail. Tracing studies in animals and human postmortem experiments are currently complemented by diffusion-weighted imaging, which enables noninvasive investigations of callosal connectivity to be conducted. In contrast to the wealth of anatomical data, little is known about the principles by which interhemispheric integration is mediated by callosal connections. Most importantly, we lack insights into the mechanisms that determine the functional role of callosal connections in a context-dependent fashion. These mechanisms can now be disclosed by models of effective connectivity that explain neuroimaging data from paradigms that manipulate interhemispheric interactions. In this article, we demonstrate that dynamic causal modeling (DCM), in conjunction with Bayesian model selection (BMS), is a powerful approach to disentangling the various factors that determine the functional role of callosal connections. We first review the theoretical foundations of DCM and BMS before demonstrating the application of these techniques to empirical data from a single subject.