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Register a new userThe role of node dynamics in shaping emergent functional connectivity patterns in the brain
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The contribution of structural connectivity to functional brain states remains poorly understood. We present a mathematical and computational study suited to assess the structure--function issue, treating a system of Jansen--Rit neural-mass nodes with heterogeneous structural connections estimated from diffusion MRI data provided by the Human Connectome Project. Via direct simulations we determine the similarity of functional (inferred from correlated activity between nodes) and structural connectivity matrices under variation of the parameters controlling single-node dynamics, highlighting a non-trivial structure--function relationship in regimes that support limit cycle oscillations. To determine their relationship, we firstly calculate network instabilities giving rise to oscillations, and the so-called `false bifurcations (for which a significant qualitative change in the orbit is observed, without a change of stability) occurring beyond this onset. We highlight that functional connectivity (FC) is inherited robustly from structure when node dynamics are poised near a Hopf bifurcation, whilst near false bifurcations, structure only weakly influences FC. Secondly, we develop a weakly-coupled oscillator description to analyse oscillatory phase-locked states and, furthermore, show how the modular structure of FC matrices can be predicted via linear stability analysis. This study thereby emphasises the substantial role that local dynamics can have in shaping large-scale functional brain states.
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The goal of the present study is to identify autism using machine learning techniques and resting-state brain imaging data, leveraging the temporal variability of the functional connections (FC) as the only information. We estimated and compared the FC variability across brain regions between typical, healthy subjects and autistic population by analyzing brain imaging data from a world-wide multi-site database known as ABIDE (Autism Brain Imaging Data Exchange). Our analysis revealed that patients diagnosed with autism spectrum disorder (ASD) show increased FC variability in several brain regions that are associated with low FC variability in the typical brain. We then used the enhanced FC variability of brain regions as features for training machine learning models for ASD classification and achieved 65% accuracy in identification of ASD versus control subjects within the dataset. We also used node strength estimated from number of functional connections per node averaged over the whole scan as features for ASD classification.The results reveal that the dynamic FC measures outperform or are comparable with the static FC measures in predicting ASD.
During slow-wave sleep, the brain is in a self-organized regime in which slow oscillations (SOs) between up- and down-states propagate across the cortex. We address the mechanism of how SOs emerge and can recruit large parts of the brain using a whole-brain model based on empirical connectivity data. Individual brain areas generate SOs that are induced by a local adaptation mechanism. Optimal fits to human resting-state fMRI data and EEG during deep sleep are found at critical values of the adaptation strength where the model produces a balance between local and global SOs with realistic spatiotemporal statistics. Local oscillations are more frequent, last shorter, and have a lower amplitude. Global oscillations spread as waves of silence across the brain, traveling from anterior to posterior regions due to the heterogeneous network structure of the human brain. Our results demonstrate the utility of whole-brain models for explaining the origin of large-scale cortical oscillations and how they are shaped by the connectome.
By focusing on melancholic features with biological homogeneity, this study aimed to identify a small number of critical functional connections (FCs) that were specific only to the melancholic type of MDD. On the resting-state fMRI data, classifiers were developed to differentiate MDD patients from healthy controls (HCs). The classification accuracy was improved from 50 % (93 MDD and 93 HCs) to 70% (66 melancholic MDD and 66 HCs), when we specifically focused on the melancholic MDD with moderate or severer level of depressive symptoms. It showed 65% accuracy for the independent validation cohort. The biomarker score distribution showed improvements with escitalopram treatments, and also showed significant correlations with depression symptom scores. This classifier was specific to melancholic MDD, and it did not generalize in other mental disorders including autism spectrum disorder (ASD, 54% accuracy) and schizophrenia spectrum disorder (SSD, 45% accuracy). Among the identified 12 FCs from 9,316 FCs between whole brain anatomical node pairs, the left DLPFC / IFG region, which has most commonly been targeted for depression treatments, and its functional connections between Precuneus / PCC, and between right DLPFC / SMA areas had the highest contributions. Given the heterogeneity of the MDD, focusing on the melancholic features is the key to achieve high classification accuracy. The identified FCs specifically predicted the melancholic MDD and associated with subjective depressive symptoms. These results suggested key FCs of melancholic depression, and open doors to novel treatments targeting these regions in the future.
The theory of communication through coherence (CTC) proposes that brain oscillations reflect changes in the excitability of neurons, and therefore the successful communication between two oscillating neural populations depends not only on the strength of the signal emitted but also on the relative phases between them. More precisely, effective communication occurs when the emitting and receiving populations are properly phase locked so the inputs sent by the emitting population arrive at the phases of maximal excitability of the receiving population. To study this setting, we consider a population rate model consisting of excitatory and inhibitory cells modelling the receiving population, and we perturb it with a time-dependent periodic function modelling the input from the emitting population. We consider the stroboscopic map for this system and compute numerically the fixed and periodic points of this map and their bifurcations as the amplitude and the frequency of the perturbation are varied. From the bifurcation diagram, we identify the phase-locked states as well as different regions of bistability. We explore carefully the dynamics emphasizing its implications for the CTC theory. In particular, we study how the input gain depends on the timing between the input and the inhibitory action of the receiving population. Our results show that naturally an optimal phase locking for CTC emerges, and provide a mechanism by which the receiving population can implement selective communication. Moreover, the presence of bistable regions, suggests a mechanism by which different communication regimes between brain areas can be established without changing the structure of the network
Obsessive-compulsive disorder (OCD) is a common psychiatric disorder with a lifetime prevalence of 2-3 percent. Recently, brain activity in the resting state is gathering attention as a new means of exploring altered functional connectivity in psychiatric disorders. Although previous resting-state functional magnetic resonance imaging studies investigated neurobiological abnormalities of patients with OCD, there are concerns that should be addressed. One concern is the validity of the hypothesis employed. Most studies used seed-based analysis of the fronto-striatal circuit, despite the potential for abnormalities in other regions. A hypothesis-free study is a promising approach in such a case, while it requires researchers to handle a dataset with large dimensions. Another concern is the reliability of biomarkers derived from a single dataset, which may be influenced by cohort-specific features. Here, by employing a recently developed machine-learning algorithm to avoid these concerns, we identified the first OCD biomarker that is generalized to an external dataset. We also demonstrated that the functional connectivities that contributed to the classification were widely distributed rather than locally constrained. Our generalizable classifier has the potential not only to deepen our understanding of the abnormal neural substrates of OCD but also to find use in clinical applications.
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