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Because of the high dimensionality of neuroimaging data, identifying a statistical test that is both valid and maximally sensitive is an important challenge. Here, we present a combination of two approaches for functional magnetic resonance imaging (fMRI) data analysis that together result in substantial improvements of the sensitivity of cluster-based statistics. The first approach is to create novel cluster definitions that optimize sensitivity to plausible effect patterns. The second is to adopt a new approach to combine test statistics with different sensitivity profiles, which we call the min(p) method. These innovations are made possible by using the randomization inference framework. In this article, we report on a set of simulations and analyses of real task fMRI data that demonstrate (a) that the proposed methods control the false-alarm rate, (b) that the sensitivity profiles of cluster-based test statistics vary depending on the cluster defining thresholds and cluster definitions, and (c) that the min(p) method for combining these test statistics results in a drastic increase of sensitivity (up to fivefold), compared to existing fMRI analysis methods. This increase in sensitivity is not at the expense of the spatial specificity of the inference.

The brain can be modelled as a network with nodes and edges derived from a range of imaging modalities: the nodes correspond to spatially distinct regions and the edges to the interactions between them. Whole-brain connectivity studies typically seek to determine how network properties change with a given categorical phenotype such as age-group, disease condition or mental state. To do so reliably, it is necessary to determine the features of the connectivity structure that are common across a group of brain scans. Given the complex interdependencies inherent in network data, this is not a straightforward task. Some studies construct a group-representative network (GRN), ignoring individual differences, while other studies analyse networks for each individual independently, ignoring information that is shared across individuals. We propose a Bayesian framework based on exponential random graph models (ERGM) extended to multiple networks to characterise the distribution of a entire population of networks. Using resting-state fMRI data from the Cam-CAN project, a study on healthy ageing, we demonstrate how our method can be used to characterise and compare the brain's functional connectivity structure across a group of young individuals and a group of old individuals.