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Register a new userA neural marker of obsessive-compulsive disorder from whole-brain functional connectivity
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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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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 neuronal circuit that controls obsessive and compulsive behaviors involves a complex network of brain regions (some with known involvement in reward processing). Among these are cortical regions, the striatum and the thalamus (which compose the CSTC pathway), limbic areas such as the amygdala and the hippocampus, and well as dopamine pathways. Abnormal dynamic behavior in this brain network is a hallmark feature of patients with increased anxiety and motor activity, like the ones affected by OCD. There is currently no clear understanding of precisely what mechanisms generates these behaviors. We attempt to investigate a collection of connectivity hypotheses of OCD by means of a computational model of the brain circuitry that governs reward and motion execution. Mathematically, we use methods from ordinary differential equations and continuous time dynamical systems. We use classical analytical methods as well as computational approaches to study phenomena in the phase plane (e.g., behavior of the systems solutions when given certain initial conditions) and in the parameter space (e.g., sensitive dependence of initial conditions). We find that different obsessive-compulsive subtypes may correspond to different abnormalities in the network connectivity profiles. We suggest that it is combinations of parameters (connectivity strengths between regions), rather the than the value of any one parameter taken independently, that provides the best basis for predicting behavior, and for understanding the heterogeneity of the illness.
Functional brain network has been widely studied to understand the relationship between brain organization and behavior. In this paper, we aim to explore the functional connectivity of brain network under a emph{multi-step} cognitive task involving with consecutive behaviors, and further understand the effect of behaviors on the brain organization. The functional brain networks are constructed base on a high spatial and temporal resolution fMRI dataset and analyzed via complex network based approach. We find that at voxel level the functional brain network shows robust small-worldness and scale-free characteristics, while its assortativity and rich-club organization are slightly restricted to order of behaviors performed. More interestingly, the functional connectivity of brain network in activated ROIs strongly correlates with behaviors and behaves obvious differences restricted to order of behaviors performed. These empirical results suggest that the brain organization has the generic properties of small-worldness and scale-free characteristics, and its diverse function connectivity emerging from activated ROIs is strongly driven by these behavioral activities via the plasticity of brain.
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.
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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