Many investigators have described olfactory dysfunction among migraineurs. Olfactory stimuli can precipitate migraine, and olfactory hallucinations can occur as auras of migraines or as part of the symptom complex. Despite many reports linking olfactory phenomena and migraine, no evaluations of the olfactory abilities of migraineurs have been documented. To begin such assessments, sixty-seven consecutive migraine patients were given Pyridine odor threshold tests. Twelve of them (18%) scored as hyposmic or anosmic. In comparison, 1% of the general population of the U.S. is hyposmic or anosmic. Aside from possible diagnostic or methodological error, several possibilities may account for our result: migraine may induce olfactory pathology; olfactory pathology may induce migraine, or; a common pathogen may induce both olfactory dysfunction and migraine. The association of migraine with the emotional component of the limbic system has long been recognized, and our results strengthen its association with the olfactory component as well. Headache patients should be tested for olfactory loss and warned of such risks as inability to detect gas leaks and spoiled food.

The human brain is organized into functional networks, whose spatial layout can be described with functional magnetic resonance imaging (fMRI). Interactions among these networks are highly dynamic and nonlinear, and evidence suggests that distinct functional network configurations interact on different levels of complexity. To gain new insights into topological properties of constellations interacting on different levels of complexity, we analyze a resting state fMRI dataset from the human connectome project. We first measure the complexity of correlational time series among resting state networks, obtained from sliding window analysis, by calculating their sample entropy. We then use graph analysis to create two functional representations of the network: A ‘high complexity network’ (HCN), whose inter-node interactions display irregular fast changes, and a ‘low complexity network’ (LCN), whose interactions are more self-similar and change more slowly in time. Graph analysis shows that the HCNs structure is significantly more globally efficient, compared to the LCNs, indicative of an architecture that allows for more integrative information processing. The LCNs layout displays significantly higher modularity than the HCNs, indicative of an architecture lending itself to segregated information processing. In the HCN, subcortical thalamic and basal ganglia networks display global hub properties, whereas cortical networks act as connector hubs in the LCN. These results can be replicated in a split sample dataset. Our findings show that investigating nonlinear properties of resting state dynamics offers new insights regarding the relative importance of specific brain regions to the two fundamental requirements for healthy brain functioning, that is, integration and segregation.

Organized patterns of system-wide neural activity adapt fluently within the brain to adjust behavioral performance to environmental demands. In major depressive disorder (MD), markedly different co-activation patterns across the brain emerge from a rather similar structural substrate. Despite the application of advanced methods to describe the functional architecture, e.g., between intrinsic brain networks (IBNs), the underlying mechanisms mediating these differences remain elusive. Here we propose a novel complementary approach for quantifying the functional relations between IBNs based on the Kuramoto model. We directly estimate the Kuramoto coupling parameters (K) from IBN time courses derived from empirical fMRI data in 24 MD patients and 24 healthy controls. We find a large pattern with a significant number of Ks depending on the disease severity score Hamilton D, as assessed by permutation testing. We successfully reproduced the dependency in an independent test data set of 44 MD patients and 37 healthy controls. Comparing the results to functional connectivity from partial correlations (FC), to phase synchrony (PS) as well as to first order auto-regressive measures (AR) between the same IBNs did not show similar correlations. In subsequent validation experiments with artificial data we find that a ground truth of parametric dependencies on artificial regressors can be recovered. The results indicate that the calculation of Ks can be a useful addition to standard methods of quantifying the brain's functional architecture.

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