Improved clinical outcome prediction in depression using neurodynamics in an emotional face-matching functional MRI task

Introduction: Approximately one in six people will experience an episode of major depressive disorder (MDD) in their lifetime. Effective treatment is hindered by subjective clinical decision-making and a lack of objective prognostic biomarkers. Functional MRI (fMRI) could provide such an objective measure but the majority of MDD studies has focused on static approaches, disregarding the rapidly changing nature of the brain. In this study, we aim to predict depression severity changes at 3 and 6 months using dynamic fMRI features.Methods: For our research, we acquired a longitudinal dataset of 32 MDD patients with fMRI scans acquired at baseline and clinical follow-ups 3 and 6 months later. Several measures were derived from an emotion face-matching fMRI dataset: activity in brain regions, static and dynamic functional connectivity between functional brain networks (FBNs) and two measures from a wavelet coherence analysis approach. All fMRI features were evaluated independently, with and without demographic and clinical parameters. Patients were divided into two classes based on changes in depression severity at both follow-ups.Results: The number of coherence clusters (nCC) between FBNs, reflecting the total number of interactions (either synchronous, anti-synchronous or causal), resulted in the highest predictive performance. The nCC-based classifier achieved 87.5% and 77.4% accuracy for the 3- and 6-months change in severity, respectively. Furthermore, regression analyses supported the potential of nCC for predicting depression severity on a continuous scale. The posterior default mode network (DMN), dorsal attention network (DAN) and two visual networks were the most important networks in the optimal nCC models. Reduced nCC was associated with a poorer depression course, suggesting deficits in sustained attention to and coping with emotion-related faces. An ensemble of classifiers with demographic, clinical and lead coherence features, a measure of dynamic causality, resulted in a 3-months clinical outcome prediction accuracy of 81.2%.Discussion: The dynamic wavelet features demonstrated high accuracy in predicting individual depression severity change. Features describing brain dynamics could enhance understanding of depression and support clinical decision-making. Further studies are required to evaluate their robustness and replicability in larger cohorts

Spatial and Temporal Quality of Brain Networks for Different Multi-Echo fMRI Combination Methods

The application of multi-echo functional magnetic resonance imaging (fMRI) studies has considerably increased in the last decade due to superior BOLD sensitivity compared to single-echo fMRI. Various methods have been developed that combine fMRI data derived at different echo times to improve data quality. Here, we evaluated five multi-echo combination schemes: ‘optimal combination’ (OC, ${\text {T}_{2}}^{\ast }$ -weighted), ${\text {T}_{2}}^{\ast }$ -FIT ( ${\text {T}_{2}}^{\ast }$ -weighted, calculated per volume), average-weighted (Avg), temporal Signal-to-Noise Ratio (tSNR) weighted, and temporal Contrast-to-Noise Ratio weighted combination. The effect of these combinations, with and without additional postprocessing, on the quality of functional resting-state networks was assessed. Sixteen healthy volunteers were scanned during a 5-minutes resting-state fMRI session. After network extraction, several quality metrics in the temporal and spatial domain were calculated for their respective time-series and spatial maps. Our results showed that OC and ${\text {T}_{2}}^{\ast }$ -FIT outperformed the other methods in both domains. Whereas the OC and ${\text {T}_{2}}^{\ast }$ -FIT time-series were found to be the least associated with artifacts, OC resulted in the highest quality spatial maps. Furthermore, spatial smoothing, bandpass filtering and ICA-AROMA merely improved networks derived from the least performing combinations (Avg and tSNR). Because similar network quality was obtained following OC and ${\text {T}_{2}}^{\ast }$ -FIT without postprocessing, we recommend future studies to implement these combinations without these postprocessing steps. This minimizes the amount of image modifications and processing, potentially leading to enhanced BOLD contrast. The results highlight the benefits of ${\text {T}_{2}}^{\ast }$ -weighted multi-echo combinations on resting-state network quality and raise its potential value in dynamic fMRI analyses or for diagnosis and prognosis purposes of neuropsychiatric disorders

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

Functional MRI in major depressive disorder:A review of findings, limitations, and future prospects

Objective diagnosis and prognosis in major depressive disorder (MDD) remains a challenge due to the absence of biomarkers based on physiological parameters or medical tests. Numerous studies have been conducted to identify functional magnetic resonance imaging-based biomarkers of depression that either objectively differentiate patients with depression from healthy subjects, predict personalized treatment outcome, or characterize biological subtypes of depression. While there are some findings of consistent functional biomarkers, there is still lack of robust data acquisition and analysis methodology. According to current findings, primarily, the anterior cingulate cortex, prefrontal cortex, and default mode network play a crucial role in MDD. Yet, there are also less consistent results and the involvement of other regions or networks remains ambiguous. We further discuss image acquisition, processing, and analysis limitations that might underlie these inconsistencies. Finally, the current review aims to address and discuss possible remedies and future opportunities that could improve the search for consistent functional imaging biomarkers of depression. Novel acquisition techniques, such as multiband and multiecho imaging, and neural network-based cleaning approaches can enhance the signal quality in limbic and frontal regions. More comprehensive analyses, such as directed or dynamic functional features or the identification of biological depression subtypes, can improve objective diagnosis or treatment outcome prediction and mitigate the heterogeneity of MDD. Overall, these improvements in functional MRI imaging techniques, processing, and analysis could advance the search for biomarkers and ultimately aid patients with MDD and their treatment course

Ultrasound detection of abnormal cerebrovascular morphology in a mouse model of sickle cell disease based on wave reflection

Sickle cell disease (SCD) is associated with a high risk of stroke, and affected individuals often have focal brain lesions termed silent cerebral infarcts. The mechanisms leading to these types of injuries are at present poorly understood. Our group has recently demonstrated a non-invasive measurement of cerebrovascular impedance and wave reflection in mice using high-frequency ultrasound in the common carotid artery. To better understand the pathophysiology in SCD, we used this approach in combination with micro-computed tomography to investigate changes in cerebrovascular morphology in the Townes mouse model of SCD. Relative to controls, the SCD mice demonstrated the following: (i) increased carotid artery diameter, blood flow and vessel wall thickness; (ii) elevated pulse wave velocity; (iii) increased reflection coefficient; and (iv) an increase in the total number of vessel segments in the brain. This study highlights the potential for wave reflection to aid the non-invasive clinical assessment of vascular pathology in SCD