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Abstract: Normal ageing is associated with a decline in episodic memory, and neuroimaging studies in older adults have shown reduced activity in prefrontal cortex and other regions critical for memory function in the young. However, older adults also activate additional regions, suggesting a degree of functional reorganisation that has been attributed variously to detrimental and adaptive changes. Evaluation of these competing hypotheses depends critically upon inferences about the relative location and distribution of activity that are not well supported by current univariate or multivariate analyses. Here, we employed a recently developed model-based multivariate ‘decoding’ approach (Friston et al., 2008) to re-analyse a rich episodic encoding dataset and examine directly how the patterns of activity change in ageing. We assessed which spatial activity patterns, within lateral prefrontal cortex, best predict successful memory formation. Bayesian model comparison showed that the older adults had more distributed and bilateral (fragmented) predictive patterns of activity in anterior inferior frontal gyrus and middle frontal gyrus. With this direct multivariate test for changes in patterns of activity, we replicate and extend earlier findings of reduced prefrontal lateralisation in ageing. These findings extend conclusions based on conventional analyses, and support the notion that ageing alters the spatial deployment of neuronal activity, to render it less spatially coherent and regionally specific. This greater distribution of activity in older adults was also linked to poorer individual memory performance, suggesting that it reflects neural ageing, rather than adaptive compensatory responses. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Abstract 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. Highlights • 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 FROM AUTHOR]

Abstract: Functional integration in the brain rests on anatomical connectivity (the presence of axonal connections) and effective connectivity (the causal influences mediated by these connections). The deployment of anatomical connections provides important constraints on effective connectivity, but does not fully determine it, because synaptic connections can be expressed functionally in a dynamic and context-dependent fashion. Although it is generally assumed that anatomical connectivity data is important to guide the construction of neurobiologically realistic models of effective connectivity; the degree to which these models actually profit from anatomical constraints has not yet been formally investigated. Here, we use diffusion weighted imaging and probabilistic tractography to specify anatomically informed priors for dynamic causal models (DCMs) of fMRI data. We constructed 64 alternative DCMs, which embodied different mappings between the probability of an anatomical connection and the prior variance of the corresponding of effective connectivity, and fitted them to empirical fMRI data from 12 healthy subjects. Using Bayesian model selection, we show that the best model is one in which anatomical probability increases the prior variance of effective connectivity parameters in a nonlinear and monotonic (sigmoidal) fashion. This means that the higher the likelihood that a given connection exists anatomically, the larger one should set the prior variance of the corresponding coupling parameter; hence making it easier for the parameter to deviate from zero and represent a strong effective connection. To our knowledge, this study provides the first formal evidence that probabilistic knowledge of anatomical connectivity can improve models of functional integration. [Copyright &y& Elsevier]

Abstract: Bayesian model selection (BMS) is a powerful method for determining the most likely among a set of competing hypotheses about the mechanisms that generated observed data. BMS has recently found widespread application in neuroimaging, particularly in the context of dynamic causal modelling (DCM). However, so far, combining BMS results from several subjects has relied on simple (fixed effects) metrics, e.g. the group Bayes factor (GBF), that do not account for group heterogeneity or outliers. In this paper, we compare the GBF with two random effects methods for BMS at the between-subject or group level. These methods provide inference on model-space using a classical and Bayesian perspective respectively. First, a classical (frequentist) approach uses the log model evidence as a subject-specific summary statistic. This enables one to use analysis of variance to test for differences in log-evidences over models, relative to inter-subject differences. We then consider the same problem in Bayesian terms and describe a novel hierarchical model, which is optimised to furnish a probability density on the models themselves. This new variational Bayes method rests on treating the model as a random variable and estimating the parameters of a Dirichlet distribution which describes the probabilities for all models considered. These probabilities then define a multinomial distribution over model space, allowing one to compute how likely it is that a specific model generated the data of a randomly chosen subject as well as the exceedance probability of one model being more likely than any other model. Using empirical and synthetic data, we show that optimising a conditional density of the model probabilities, given the log-evidences for each model over subjects, is more informative and appropriate than both the GBF and frequentist tests of the log-evidences. In particular, we found that the hierarchical Bayesian approach is considerably more robust than either of the other approaches in the presence of outliers. We expect that this new random effects method will prove useful for a wide range of group studies, not only in the context of DCM, but also for other modelling endeavours, e.g. comparing different source reconstruction methods for EEG/MEG or selecting among competing computational models of learning and decision-making. [Copyright &y& Elsevier]