Objective biomarkers of depression: A study of Granger causality and wavelet coherence in resting-state fMRI.

BACKGROUND AND PURPOSE: The lack of a robust diagnostic biomarker makes understanding depression from a neurobiological standpoint an important goal, especially in the context of brain imaging. METHODS: In this study, we aim to create novel image-based features for objective diagnosis of depression. Resting-state network time series are used to investigate neurodynamics with the help of wavelet coherence and Granger causality (G-causality). Three new features are introduced: total wavelet coherence, wavelet lead coherence, and wavelet coherence blob analysis. The fourth feature, pair-wise conditional G-causality, is used to establish the causality between resting-state networks. We use the proposed features to classify depression in adult subjects. RESULTS: We obtained an accuracy of 86% in the wavelet lead coherence, 80% in Granger causality, and 86% in wavelet coherence blob analysis. Subjects with depression showed hyperconnectivity between the dorsal attention network and the auditory network as well as between the posterior default mode network and the dorsal attention network. Hypoconnectivity was found between the anterior default mode network and the auditory network as well as the right frontoparietal network and the lateral visual network. An abnormal co-activation pattern was found between cerebellum and the lateral motor network according to the wavelet coherence blob analysis. CONCLUSION: Based on abnormal functional dynamics between brain networks, we were able to identify subjects with depression with high accuracy. The findings of this study contribute to the understanding of the impaired emotional and attention processing associated with depression, as well as decreased motor activity.

Emulative, coherent, and causal dynamics between large-scale brain networks are neurobiomarkers of Accelerated Cognitive Ageing in epilepsy.

Accelerated cognitive ageing (ACA) is an ageing co-morbidity in epilepsy that is diagnosed through the observation of an evident IQ decline of more than 1 standard deviation (15 points) around the age of 50 years old. To understand the mechanism of action of this pathology, we assessed brain dynamics with the use of resting-state fMRI data. In this paper, we present novel and promising methods to extract brain dynamics between large-scale resting-state networks: the emulative power, wavelet coherence, and granger causality between the networks were extracted in two resting-state sessions of 24 participants (10 ACA, 14 controls). We also calculated the widely used static functional connectivity to compare the methods. To find the best biomarkers of ACA, and have a better understanding of this epilepsy co-morbidity we compared the aforementioned between-network neurodynamics using classifiers and known machine learning algorithms; and assessed their performance. Results show that features based on the evolutionary game theory on networks approach, the emulative powers, are the best descriptors of the co-morbidity, using dynamics associated with the default mode and dorsal attention networks. With these dynamic markers, linear discriminant analysis could identify ACA patients at 82.9% accuracy. Using wavelet coherence features with decision-tree algorithm, and static functional connectivity features with support vector machine, ACA could be identified at 77.1% and 77.9% accuracy respectively. Granger causality fell short of being a relevant biomarker with best classifiers having an average accuracy of 67.9%. Combining the features based on the game theory, wavelet coherence, Granger-causality, and static functional connectivity- approaches increased the classification performance up to 90.0% average accuracy using support vector machine with a peak accuracy of 95.8%. The dynamics of the networks that lead to the best classifier performances are known to be challenged in elderly. Since our groups were age-matched, the results are in line with the idea of ACA patients having an accelerated cognitive decline. This classification pipeline is promising and could help to diagnose other neuropsychiatric disorders, and contribute to the field of psychoradiology.

A Bayesian method for inference of effective connectivity in brain networks for detecting the Mozart effect.

Several studies claim that listening to Mozart music affects cognition and can be used to treat neurological conditions like epilepsy. Research into this Mozart effect has not addressed how dynamic interactions between brain networks, i.e. effective connectivity, are affected. The Granger-causality analysis is often used to infer effective connectivity. First, we investigate if a new method, Bayesian topology identification, can be used as an alternative. Both methods are evaluated on simulation data, where the Bayesian method outperforms the Granger-causality analysis in the inference of connectivity graphs of dynamic networks, especially for short data lengths. In the second part, the Bayesian method is extended to enable the inference of changes in effective connectivity between groups of subjects. Next, we apply both methods to fMRI scans of 16 healthy subjects, who were scanned before and after the exposure to Mozart's sonata K448 at least 2 hours a day for 7 days. Here, we investigate if the effective connectivity of the subjects significantly changed after listening to Mozart music. The Bayesian method detected changes in effective connectivity between networks related to cognitive processing and control in the connection from the central executive to the superior sensori-motor network, in the connection from the posterior default mode to the fronto-parietal right network, and in the connection from the anterior default mode to the dorsal attention network. This last connection was only detected in a subgroup of subjects with a longer listening duration. Only in this last connection, an effect was found by the Granger-causality analysis.

Accelerated Cognitive Ageing in Epilepsy: A Neuropsychological Evaluation of Cognitive Deterioration.

OBJECTIVE: Shed light on cognitive deterioration in Accelerated Cognitive Ageing (ACA) in epilepsy from a neuropsychological point of view in order to improve clinical diagnostics. METHODS: We compared the IQ-profile including GAI, OPIE IV-premorbid IQ and deterioration-scores of 21 epilepsy patients with ACA with 21 matched epilepsy patients without ACA (Epilepsy Controls) and 16 age- and education-matched Healthy Controls. Memory was also evaluated. RESULTS: Premorbid IQs were equal in all groups. Deterioration was apparent in the ACA-group in the WAIS-IV FSIQ and PRI, whereas no deterioration was found in the two control groups. PSI was impaired in both epilepsy groups, though with more impairment seen in the ACA-group. The VCI remained unimpaired. The FSIQ-GAI discrepancy was equal in both patient groups and significantly larger than in the Healthy Controls. WMS-IV memory indices were of average level in all groups. Memory impairment in ACA was not statistically different from the Epilepsy Controls. 85.7% of ACA-patients could be correctly classified through factors DET_FSIQ and PSI. CONCLUSIONS: Cognitive deterioration in ACA is characterized by an average drop of 19 IQ-points in FSIQ and PRI. Verbal abilities remain unimpaired. Impairments in fluid functions compromise cognitive abilities in epilepsy, but only partially contribute to cognitive deterioration in ACA. PSI proved to have some diagnostic value in differentiating epilepsy patients from healthy controls, but fails to differentiate between ACA and Epilepsy Controls. A comparison made between OPIE-IV equations and obtained IQs leads to a significant better detection of cognitive deterioration in epilepsy than the use of GAI-FSIQ discrepancies alone.

Brain resting-state networks in adolescents with high-functioning autism: Analysis of spatial connectivity and temporal neurodynamics.

Introduction: Autism spectrum disorder (ASD) is mainly characterized by functional and communication impairments as well as restrictive and repetitive behavior. The leading hypothesis for the neural basis of autism postulates globally abnormal brain connectivity, which can be assessed using functional magnetic resonance imaging (fMRI). Even in the absence of a task, the brain exhibits a high degree of functional connectivity, known as intrinsic, or resting-state, connectivity. Global default connectivity in individuals with autism versus controls is not well characterized, especially for a high-functioning young population. The aim of this study is to test whether high-functioning adolescents with ASD (HFA) have an abnormal resting-state functional connectivity. Materials and Methods: We performed spatial and temporal analyses on resting-state networks (RSNs) in 13 HFA adolescents and 13 IQ- and age-matched controls. For the spatial analysis, we used probabilistic independent component analysis (ICA) and a permutation statistical method to reveal the RSN differences between the groups. For the temporal analysis, we applied Granger causality to find differences in temporal neurodynamics. Results: Controls and HFA display very similar patterns and strengths of resting-state connectivity. We do not find any significant differences between HFA adolescents and controls in the spatial resting-state connectivity. However, in the temporal dynamics of this connectivity, we did find differences in the causal effect properties of RSNs originating in temporal and prefrontal cortices. Conclusion: The results show a difference between HFA and controls in the temporal neurodynamics from the ventral attention network to the salience-executive network: a pathway involving cognitive, executive, and emotion-related cortices. We hypothesized that this weaker dynamic pathway is due to a subtle trigger challenging the cognitive state prior to the resting state.

Wavelet coherence-based classifier: A resting-state functional MRI study on neurodynamics in adolescents with high-functioning autism.

BACKGROUND AND OBJECTIVE: The autism spectrum disorder (ASD) diagnosis requires a long and elaborate procedure. Due to the lack of a biomarker, the procedure is subjective and is restricted to evaluating behavior. Several attempts to use functional MRI as an assisting tool (as classifier) have been reported, but they barely reach an accuracy of 80%, and have not usually been replicated or validated with independent datasets. Those attempts have used functional connectivity and structural measurements. There is, nevertheless, evidence that not the topology of networks, but their temporal dynamics is a key feature in ASD. We therefore propose a novel MRI-based ASD biomarker by analyzing temporal brain dynamics in resting-state fMRI. METHODS: We investigate resting-state fMRI data from 2 independent datasets of adolescents: our in-house data (12 ADS, 12 controls), and the Leuven dataset (12 ASD, 18 controls, from Leuven university). Using independent component analysis we obtain relevant socio-executive resting-state networks (RSNs) and their associated time series. Upon these time series we extract wavelet coherence maps. Using these maps, we calculate our dynamics metric: time of in-phase coherence. This novel metric is then used to train classifiers for autism diagnosis. Leave-one-out cross validation is applied for performance evaluation. To assess inter-site robustness, we also train our classifiers on the in-house data, and test them on the Leuven dataset. RESULTS: We distinguished ASD from non-ASD adolescents at 86.7% accuracy (91.7% sensitivity, 83.3% specificity). In the second experiment, using Leuven dataset, we also obtained the classification performance at 86.7% (83.3% sensitivity, and 88.9% specificity). Finally we classified the Leuven dataset, with classifiers trained with our in-house data, resulting in 80% accuracy (100% sensitivity, 66.7% specificity). CONCLUSIONS: This study shows that change in the coherence of temporal neurodynamics is a biomarker of ASD, and wavelet coherence-based classifiers lead to robust and replicable results and could be used as an objective diagnostic tool for ASD.