To provide an effective substrate for cognitive processes, functional brain networks should be able to reorganize and coordinate on a sub-second temporal scale. We used magnetoencephalography recordings of spontaneous activity to characterize whole-brain functional connectivity dynamics at high temporal resolution. Using a novel approach that identifies the points in time at which unique patterns of activity recur, we reveal transient (100–200 ms) brain states with spatial topographies similar to those of well-known resting state networks. By assessing temporal changes in the occurrence of these states, we demonstrate that within-network functional connectivity is underpinned by coordinated neuronal dynamics that fluctuate much more rapidly than has previously been shown. We further evaluate cross-network interactions, and show that anticorrelation between the default mode network and parietal regions of the dorsal attention network is consistent with an inability of the system to transition directly between two transient brain states.DOI: http://dx.doi.org/10.7554/eLife.01867.001

BackgroundDespite many successes, the case-control approach is problematic in biomedical science. It introduces an artificial symmetry whereby all clinical groups (e.g., patients and control subjects) are assumed to be well defined, when biologically they are often highly heterogeneous. By definition, it also precludes inference over the validity of the diagnostic labels. In response, the National Institute of Mental Health Research Domain Criteria proposes to map relationships between symptom dimensions and broad behavioral and biological domains, cutting across diagnostic categories. However, to date, Research Domain Criteria have prompted few methods to meaningfully stratify clinical cohorts.MethodsWe introduce normative modeling for parsing heterogeneity in clinical cohorts, while allowing predictions at an individual subject level. This approach aims to map variation within the cohort and is distinct from, and complementary to, existing approaches that address heterogeneity by employing clustering techniques to fractionate cohorts. To demonstrate this approach, we mapped the relationship between trait impulsivity and reward-related brain activity in a large healthy cohort (N = 491).ResultsWe identify participants who are outliers within this distribution and show that the degree of deviation (outlier magnitude) relates to specific attention-deficit/hyperactivity disorder symptoms (hyperactivity, but not inattention) on the basis of individualized patterns of abnormality.ConclusionsNormative modeling provides a natural framework to study disorders at the individual participant level without dichotomizing the cohort. Instead, disease can be considered as an extreme of the normal range or as—possibly idiosyncratic—deviation from normal functioning. It also enables inferences over the degree to which behavioral variables, including diagnostic labels, map onto biology.

A completely automated algorithm to detect poor-quality electrocardiograms (ECGs) is described. The algorithm is based on both novel and previously published signal quality metrics, originally designed for intensive care monitoring. The algorithms have been adapted for use on short (5-10 s) single- and multi-lead ECGs. The metrics quantify spectral energy distribution, higher order moments and inter-channel and inter-algorithm agreement. Seven metrics were calculated for each channel (84 features in all) and presented to either a multi-layer perceptron artificial neural network or a support vector machine (SVM) for training on a multiple-annotator labelled and adjudicated training dataset. A single-lead version of the algorithm was also developed in a similar manner. Data were drawn from the PhysioNet Challenge 2011 dataset where binary labels were available, on 1500 12-lead ECGs indicating whether the entire recording was acceptable or unacceptable for clinical interpretation. We re-annotated all the leads in both the training set (1000 labelled ECGs) and test dataset (500 12-lead ECGs where labels were not publicly available) using two independent annotators, and a third for adjudication of differences. We found that low-quality data accounted for only 16% of the ECG leads. To balance the classes (between high and low quality), we created extra noisy data samples by adding noise from PhysioNet's noise stress test database to some of the clean 12-lead ECGs. No data were shared between training and test sets. A classification accuracy of 98% on the training data and 97% on the test data were achieved. Upon inspection, incorrectly classified data were found to be borderline cases which could be classified either way. If these cases were more consistently labelled, we expect our approach to achieve an accuracy closer to 100%.

We propose a methodology for extracting social network structure from spatio-temporal datasets that describe timestamped occurrences of individuals. Our approach identifies temporal regions of dense agent activity and links are drawn between individuals based on their cooccurrences across these 'gathering events'. The statistical significance of these connections is then tested against an appropriate null model. Such a framework allows us to exploit the wealth of analytical and computational tools of network analysis in settings where the underlying connectivity pattern between interacting agents (commonly termed the adjacency matrix) is not given a priori. We perform experiments on two large-scale datasets (greater than 10 6 points) of great tit Parus major wild bird foraging records and illustrate the use of this approach by examining the temporal dynamics of pairing behaviour, a process that was previously very hard to observe. We show that established pair bonds are maintained continuously, whereas new pair bonds form at variable times before breeding, but are characterized by a rapid development of network proximity. The method proposed here is general, and can be applied to any system with information about the temporal co-occurrence of interacting agents.