During rest, brain activity is synchronized between different regions widely distributed throughout the brain, forming functional networks. However, the molecular mechanisms supporting functional connectivity remain undefined. We show that functional brain networks defined with resting-state functional magnetic resonance imaging can be recapitulated by using measures of correlated gene expression in a post mortem brain tissue data set. The set of 136 genes we identify is significantly enriched for ion channels. Polymorphisms in this set of genes significantly affect resting-state functional connectivity in a large sample of healthy adolescents. Expression levels of these genes are also significantly associated with axonal connectivity in the mouse. The results provide convergent, multimodal evidence that resting-state functional networks correlate with the orchestrated activity of dozens of genes linked to ion channel activity and synaptic function.

Functional connectivity (FC) as measured by correlation between fMRI BOLD time courses of distinct brain regions has revealed meaningful organization of spontaneous fluctuations in the resting brain. However, an increasing amount of evidence points to non-stationarity of FC; i.e., FC dynamically changes over time reflecting additional and rich information about brain organization, but representing new challenges for analysis and interpretation. Here, we propose a data-driven approach based on principal component analysis (PCA) to reveal hidden patterns of coherent FC dynamics across multiple subjects. We demonstrate the feasibility and relevance of this new approach by examining the differences in dynamic FC between 13 healthy control subjects and 15 minimally disabled relapse-remitting multiple sclerosis patients. We estimated whole-brain dynamic FC of regionally-averaged BOLD activity using sliding time windows. We then used PCA to identify FC patterns, termed "eigenconnectivities", that reflect meaningful patterns in FC fluctuations. We then assessed the contributions of these patterns to the dynamic FC at any given time point and identified a network of connections centered on the default-mode network with altered contribution in patients. Our results complement traditional stationary analyses, and reveal novel insights into brain connectivity dynamics and their modulation in a neurodegenerative disease.© 2013 Elsevier Inc. All rights reserved. IntroductionSpontaneous fluctuations of the functional MRI (fMRI) bloodoxygen-level-dependent (BOLD) signal are not random but temporally coherent between distinct brain regions. While these fluctuations were long considered as "noise", Biswal et al. (1995) showed that fluctuations of motor areas were correlated even in the absence of a motor task. Several other networks of coherent BOLD activity between remote brain regions have since been identified, including visual, auditory, language and attention networks, and a network called the "default mode network" (DMN) which reduces its activity during attentiondemanding tasks. These networks of regions with coherent activity during rest are consistent across subjects and closely resemble the brain's functional organization of evoked responses (Damoiseaux et al., 2006;Fox and Raichle, 2007;Laird et al., 2011;Smith et al., 2009). Coherent BOLD activity persists during sleep and in anesthetized monkeys, suggesting that it reflects a fundamental property of the brain's functional organization (Larson-Prior et al., 2009;Vincent et al., 2007).Coherent BOLD activity, known as "functional connectivity" (FC), is modulated by learning (Bassett et al., 2011), cognitive and affective states (Cribben et al., 2012;Ekman et al., 2012;Eryilmaz et al., 2011;Richiardi et al., 2011;Shirer et al., 2012) and also spontaneously Chang and Glover, 2010; Kitzbichler et al., 2009). Chang andGlover (2010) showed that FC between the posterior cingulate cortex, a key region of the default mode network, and various other brain regions was highly dy...

In the past years, mass univariate statistical analyses of neuroimaging data have been complemented by the use of multivariate pattern analyses, especially based on machine learning models. While these allow an increased sensitivity for the detection of spatially distributed effects compared to univariate techniques, they lack an established and accessible software framework. The goal of this work was to build a toolbox comprising all the necessary functionalities for multivariate analyses of neuroimaging data, based on machine learning models. The “Pattern Recognition for Neuroimaging Toolbox” (PRoNTo) is open-source, cross-platform, MATLAB-based and SPM compatible, therefore being suitable for both cognitive and clinical neuroscience research. In addition, it is designed to facilitate novel contributions from developers, aiming to improve the interaction between the neuroimaging and machine learning communities. Here, we introduce PRoNTo by presenting examples of possible research questions that can be addressed with the machine learning framework implemented in PRoNTo, and cannot be easily investigated with mass univariate statistical analysis.