Zening Fu

Many mental illnesses share overlapping or similar clinical symptoms, confounding the diagnosis. It is important to systematically characterize the degree to which unique and similar changing patterns are reflective of brain disorders. Increasing sharing initiatives on neuroimaging data have provided unprecedented opportunities to study brain disorders. However, it is still an open question on replicating and translating findings across studies. Standardized approaches for capturing reproducible and comparable imaging markers are greatly needed. Here, we propose a pipeline based on the priori-driven independent component analysis, NeuroMark, which is capable of estimating brain functional network measures from functional magnetic resonance imaging (fMRI) data that can be used to link brain network abnormalities among different datasets, studies, and disorders. NeuroMark automatically estimates features adaptable to each individual subject and comparable across datasets/studies/disorders by taking advantage of the reliable brain network templates extracted from 1828 healthy controls as guidance. Four studies including 2442 subjects were conducted spanning six brain disorders (schizophrenia, autism spectrum disorder, mild cognitive impairment, Alzheimer's disease, bipolar disorder, and major depressive disorder) to evaluate validity of the proposed pipeline from different perspectives (replication of brain abnormalities, cross-study comparison, identification of subtle brain changes, and multi-disorder classification using identified biomarkers). Our results highlight that NeuroMark effectively identified replicated brain network abnormalities of schizophrenia across different datasets; revealed interesting neural clues on the overlap and specificity between autism and schizophrenia; demonstrated brain functional impairments present to varying degrees in mild cognitive impairments and Alzheimer's disease; and captured biomarkers that achieved good performance in classifying bipolar disorder and major depressive disorder.

Brain functional imaging data, especially functional magnetic resonance imaging (fMRI) data, have been employed to reflect functional integration of the brain. Alteration in brain functional connectivity (FC) is expected to provide potential biomarkers for classifying or predicting brain disorders. In this paper, we present a comprehensive review in order to provide guidance about the available brain FC measures and typical classification strategies. We survey the state-of-the-art FC analysis methods including widely used static functional connectivity (SFC) and more recently proposed dynamic functional connectivity (DFC). Temporal correlations among regions of interest (ROIs), data-driven spatial network and functional network connectivity (FNC) are often computed to reflect SFC from different angles. SFC can be extended to DFC using a sliding-window framework, and intrinsic connectivity states along the time-varying connectivity patterns are typically extracted using clustering or decomposition approaches. We also briefly summarize window-less DFC approaches. Subsequently, we highlight various strategies for feature selection including the filter, wrapper and embedded methods. In terms of model building, we include traditional classifiers as well as more recently applied deep learning methods. Moreover, we review representative applications with remarkable classification accuracy for psychosis and mood disorders, neurodevelopmental disorder, and neurological disorders using fMRI data. Schizophrenia, bipolar disorder, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), Alzheimer's disease and mild cognitive impairment (MCI) are discussed. Finally, challenges in the field are pointed out with respect to the inaccurate diagnosis labeling, the abundant number of possible features and the difficulty in validation. Some suggestions for future work are also provided.

Abstract Recent critical commentaries unfavorably compare deep learning (DL) with standard machine learning (SML) approaches for brain imaging data analysis. However, their conclusions are often based on pre-engineered features depriving DL of its main advantage — representation learning. We conduct a large-scale systematic comparison profiled in multiple classification and regression tasks on structural MRI images and show the importance of representation learning for DL. Results show that if trained following prevalent DL practices, DL methods have the potential to scale particularly well and substantially improve compared to SML methods, while also presenting a lower asymptotic complexity in relative computational time, despite being more complex. We also demonstrate that DL embeddings span comprehensible task-specific projection spectra and that DL consistently localizes task-discriminative brain biomarkers. Our findings highlight the presence of nonlinearities in neuroimaging data that DL can exploit to generate superior task-discriminative representations for characterizing the human brain.

OBJECTIVE: To investigate the dynamic functional connectivity of thalamocortical networks in interictal migraine patients and whether clinical features are associated with abnormal connectivity. METHODS: We investigated dynamic functional network connectivity (dFNC) of the migraine brain in 89 interictal migraine patients and 70 healthy controls. We focused on the temporal properties of thalamocortical connectivity using sliding window cross-correlation, clustering state analysis, and graph-theory methods. Relationships between clinical symptoms and abnormal dFNC were evaluated using a multivariate linear regression model. RESULTS: Five dFNC brain states were identified to characterize and compare dynamic functional connectivity patterns. We demonstrated that migraineurs spent more time in a strongly interconnected between-network state, but they spent less time in a sparsely connected state. Interestingly, we found that abnormal posterior thalamus (pulvinar nucleus) dFNC with the visual cortex and the precuneus were significantly correlated with headache frequency of migraine. Further topologic measures revealed that migraineurs had significantly lower efficiency of information transfer in both global and local dFNC. CONCLUSION: Our results demonstrated a transient pathologic state with atypical thalamocortical connectivity in migraineurs and extended current findings regarding abnormal thalamocortical networks and dysrhythmia in migraine.