Lubin Wang

Identifying major depression using whole-brain functional connectivity: a multivariate pattern analysis

Recent resting-state functional connectivity magnetic resonance imaging studies have shown significant group differences in several regions and networks between patients with major depressive disorder and healthy controls. The objective of the present study was to investigate the whole-brain resting-state functional connectivity patterns of depressed patients, which can be used to test the feasibility of identifying major depressive individuals from healthy controls. Multivariate pattern analysis was employed to classify 24 depressed patients from 29 demographically matched healthy volunteers. Permutation tests were used to assess classifier performance. The experimental results demonstrate that 94.3% (P < 0.0001) of subjects were correctly classified by leave-one-out cross-validation, including 100% identification of all patients. The majority of the most discriminating functional connections were located within or across the default mode network, affective network, visual cortical areas and cerebellum, thereby indicating that the disease-related resting-state network alterations may give rise to a portion of the complex of emotional and cognitive disturbances in major depression. Moreover, the amygdala, anterior cingulate cortex, parahippocampal gyrus and hippocampus, which exhibit high discriminative power in classification, may play important roles in the pathophysiology of this disorder. The current study may shed new light on the pathological mechanism of major depression and suggests that whole-brain resting-state functional connectivity magnetic resonance imaging may provide potential effective biomarkers for its clinical diagnosis.

Discriminative analysis of resting-state functional connectivity patterns of schizophrenia using low dimensional embedding of fMRI

Recently, a functional disconnectivity hypothesis of schizophrenia has been proposed for the physiological explanation of behavioral syndromes of this complex mental disorder. In this paper, we aim at further examining whether syndromes of schizophrenia could be decoded by some special spatiotemporal patterns of resting-state functional connectivity. We designed a data-driven classifier based on machine learning to extract highly discriminative functional connectivity features and to discriminate schizophrenic patients from healthy controls. The proposed classifier consisted of two separate steps. First, we used feature selection based on a correlation coefficient method to extract highly discriminative regions and construct the optimal feature set for classification. Then, an unsupervised-learning classifier combining low-dimensional embedding and self-organized clustering of fMRI was trained to discriminate schizophrenic patients from healthy controls. The performance of the classifier was tested using a leave-one-out cross-validation strategy. The experimental results demonstrated not only high classification accuracy (93.75% for schizophrenic patients, 75.0% for healthy controls), but also good generalization and stability with respect to the number of extracted features. In addition, some functional connectivities between certain brain regions of the cerebellum and frontal cortex were found to exhibit the highest discriminative power, which might provide further evidence for the cognitive dysmetria hypothesis of schizophrenia. This primary study demonstrated that machine learning could extract exciting new information from the resting-state activity of a brain with schizophrenia, which might have potential ability to improve current diagnosis and treatment evaluation of schizophrenia.

A Treatment-Resistant Default Mode Subnetwork in Major Depression

BACKGROUND Previous studies have suggested that the default mode network (DMN) plays a central role in the physiopathology of major depressive disorder (MDD). However, the effect of antidepressant treatment on functional connectivity within the DMN has yet to be established. Considering the very high rates of relapse in recovered subjects, we hypothesized that abnormalities in DMN functional connectivity would persist in recovered MDD subjects. METHODS Resting state functional magnetic resonance imaging images were collected from 24 MDD patients and 29 healthy control subjects. After 12 weeks of antidepressant treatment, 18 recovered MDD subjects were scanned again. Group independent component analysis was performed to decompose the resting state images into spatially independent components. Default mode subnetworks were identified using a template based on previous studies. Group differences in the ensuing subnetworks were tested using two-sample t tests. RESULTS Two spatially independent default mode subnetworks were detected in all subjects: the anterior subnetwork and the posterior subnetwork. Both subnetworks showed increased functional connectivity in pretreatment MDD subjects, relative to control subjects. Differences in the posterior subnetwork were normalized after antidepressant treatment, while abnormal functional connectivity persisted within the anterior subnetwork. CONCLUSIONS Our findings suggest a dissociation of the DMN into subnetworks, where persistent abnormal functional connectivity within the anterior subnetwork in recovered MDD subjects may constitute a biomarker of asymptomatic depression and potential for relapse.

Combined structural and resting-state functional MRI analysis of sexual dimorphism in the young adult human brain: An MVPA approach

There has been growing interest recently in the use of multivariate pattern analysis (MVPA) to decode information from high-dimensional neuroimaging data. The present study employed a support vector machine-based MVPA approach to identify the complex patterns of sex differences in brain structure and resting-state function. We also aimed to assess the role of anatomy on functional sex differences during rest. One hundred and forty healthy young Chinese adults (70 men and 70 women) underwent structural and resting-state functional MRI scans. Gray matter density and regional homogeneity (ReHo) were used to map brain structure and resting-state function, respectively. After combining these two feature vectors into one union-vector, a pattern classifier was designed using principal component analysis and linear support vector machine to identify brain areas that had distinct characteristics between the groups. We found that: (1) male and female brains were different with a mean classification accuracy of 89%; (2) sex differences in gray matter density were widely distributed in the brain, notably in the occipital lobe and the cerebellum; (3) men primarily showed higher ReHo in their right hemispheres and women tended to show greater ReHo in their left hemispheres; (4) about 50% of brain areas with functional sex differences exhibited significant positive correlations between gray matter density and ReHo. Our results suggest that sex is an important factor that account for interindividual variability in the healthy brain.

Increased Cortical-Limbic Anatomical Network Connectivity in Major Depression Revealed by Diffusion Tensor Imaging

Magnetic resonance imaging studies have reported significant functional and structural differences between depressed patients and controls. Little attention has been given, however, to the abnormalities in anatomical connectivity in depressed patients. In the present study, we aim to investigate the alterations in connectivity of whole-brain anatomical networks in those suffering from major depression by using machine learning approaches. Brain anatomical networks were extracted from diffusion magnetic resonance images obtained from both 22 first-episode, treatment-naive adults with major depressive disorder and 26 matched healthy controls. Using machine learning approaches, we differentiated depressed patients from healthy controls based on their whole-brain anatomical connectivity patterns and identified the most discriminating features that represent between-group differences. Classification results showed that 91.7% (patients = 86.4%, controls = 96.2%; permutation test, p<0.0001) of subjects were correctly classified via leave-one-out cross-validation. Moreover, the strengths of all the most discriminating connections were increased in depressed patients relative to the controls, and these connections were primarily located within the cortical-limbic network, especially the frontal-limbic network. These results not only provide initial steps toward the development of neurobiological diagnostic markers for major depressive disorder, but also suggest that abnormal cortical-limbic anatomical networks may contribute to the anatomical basis of emotional dysregulation and cognitive impairments associated with this disease.

Altered default mode and fronto-parietal network subsystems in patients with schizophrenia and their unaffected siblings

The complex symptoms of schizophrenia have recently been linked to disrupted neural circuits and corresponding malfunction of two higher-order intrinsic brain networks: The default mode network (DMN) and the fronto-parietal network (FPN). These networks are both functionally heterogeneous and consist of multiple subsystems. However, the extent to which these subsystems make differential contributions to disorder symptoms and to what degree such abnormalities occur in unaffected siblings have yet to be clarified. We used resting-state functional MRI (rs-fMRI) to examine group differences in intra- and inter-connectivity of subsystems within the two neural networks, across a sample of patients with schizophrenia (n=24), their unaffected siblings (n=25), and healthy controls (n=22). We used group independent component analysis (gICA) to identify four network subsystems, including anterior and posterior portions of the DMN (aDMN, pDMN) as well as left- and right-lateralized portions of the FPN (lFPN, rFPN). Intra-connectivity is defined as neural coherence within a subsystem whereas inter-connectivity refers to functional connectivity between subsystems. In terms of intra-connectivity, patients and siblings shared dysconnection within the aDMN and two FPN subsystems, while both groups preserved connectivity within the pDMN. In terms of inter-connectivity, all groups exhibited positive connections between FPN and DMN subsystems, with patients having even stronger interaction between rFPN and aDMN than the controls, a feature that may underlie their psychotic symptoms. Our results implicate that DMN subsystems exhibit different liabilities to the disease risk while FPN subsystems demonstrate distinct inter-connectivity alterations. These dissociating manners between network subsystems explicitly suggest their differentiating roles to the disease susceptibility and manifestation.

Decreased Thalamocortical Functional Connectivity after 36 Hours of Total Sleep Deprivation: Evidence from Resting State fMRI

Objectives The thalamus and cerebral cortex are connected via topographically organized, reciprocal connections, which hold a key function in segregating internally and externally directed awareness information. Previous task-related studies have revealed altered activities of the thalamus after total sleep deprivation (TSD). However, it is still unclear how TSD impacts on the communication between the thalamus and cerebral cortex. In this study, we examined changes of thalamocortical functional connectivity after 36 hours of total sleep deprivation by using resting state function MRI (fMRI). Materials and Methods Fourteen healthy volunteers were recruited and performed fMRI scans before and after 36 hours of TSD. Seed-based functional connectivity analysis was employed and differences of thalamocortical functional connectivity were tested between the rested wakefulness (RW) and TSD conditions. Results We found that the right thalamus showed decreased functional connectivity with the right parahippocampal gyrus, right middle temporal gyrus and right superior frontal gyrus in the resting brain after TSD when compared with that after normal sleep. As to the left thalamus, decreased connectivity was found with the right medial frontal gyrus, bilateral middle temporal gyri and left superior frontal gyrus. Conclusion These findings suggest disruptive changes of the thalamocortical functional connectivity after TSD, which may lead to the decline of the arousal level and information integration, and subsequently, influence the human cognitive functions.

Altered Resting-State Amygdala Functional Connectivity after 36 Hours of Total Sleep Deprivation

Objectives Recent neuroimaging studies have identified a potentially critical role of the amygdala in disrupted emotion neurocircuitry in individuals after total sleep deprivation (TSD). However, connectivity between the amygdala and cerebral cortex due to TSD remains to be elucidated. In this study, we used resting-state functional MRI (fMRI) to investigate the functional connectivity changes of the basolateral amygdala (BLA) and centromedial amygdala (CMA) in the brain after 36 h of TSD. Materials and Methods Fourteen healthy adult men aged 25.9±2.3 years (range, 18–28 years) were enrolled in a within-subject crossover study. Using the BLA and CMA as separate seed regions, we examined resting-state functional connectivity with fMRI during rested wakefulness (RW) and after 36 h of TSD. Results TSD resulted in a significant decrease in the functional connectivity between the BLA and several executive control regions (left dorsolateral prefrontal cortex [DLPFC], right dorsal anterior cingulate cortex [ACC], right inferior frontal gyrus [IFG]). Increased functional connectivity was found between the BLA and areas including the left posterior cingulate cortex/precuneus (PCC/PrCu) and right parahippocampal gyrus. With regard to CMA, increased functional connectivity was observed with the rostral anterior cingulate cortex (rACC) and right precentral gyrus. Conclusion These findings demonstrate that disturbance in amygdala related circuits may contribute to TSD psychophysiology and suggest that functional connectivity studies of the amygdala during the resting state may be used to discern aberrant patterns of coupling within these circuits after TSD.

Discriminative analysis of non-linear brain connectivity in schizophrenia: an fMRI Study

Background: Dysfunctional integration of distributed brain networks is believed to be the cause of schizophrenia, and resting-state functional connectivity analyses of schizophrenia have attracted considerable attention in recent years. Unfortunately, existing functional connectivity analyses of schizophrenia have been mostly limited to linear associations. Objective: The objective of the present study is to evaluate the discriminative power of non-linear functional connectivity and identify its changes in schizophrenia. Method: A novel measure utilizing the extended maximal information coefficient was introduced to construct non-linear functional connectivity. In conjunction with multivariate pattern analysis, the new functional connectivity successfully discriminated schizophrenic patients from healthy controls with relative higher accuracy rate than the linear measure. Result: We found that the strength of the identified non-linear functional connections involved in the classification increased in patients with schizophrenia, which was opposed to its linear counterpart. Further functional network analysis revealed that the changes of the non-linear and linear connectivity have similar but not completely the same spatial distribution in human brain. Conclusion: The classification results suggest that the non-linear functional connectivity provided useful discriminative power in diagnosis of schizophrenia, and the inverse but similar spatial distributed changes between the non-linear and linear measure may indicate the underlying compensatory mechanism and the complex neuronal synchronization underlying the symptom of schizophrenia.

Sparse Representation of Brain Aging: Extracting Covariance Patterns from Structural MRI

An enhanced understanding of how normal aging alters brain structure is urgently needed for the early diagnosis and treatment of age-related mental diseases. Structural magnetic resonance imaging (MRI) is a reliable technique used to detect age-related changes in the human brain. Currently, multivariate pattern analysis (MVPA) enables the exploration of subtle and distributed changes of data obtained from structural MRI images. In this study, a new MVPA approach based on sparse representation has been employed to investigate the anatomical covariance patterns of normal aging. Two groups of participants (group 1∶290 participants; group 2∶56 participants) were evaluated in this study. These two groups were scanned with two 1.5 T MRI machines. In the first group, we obtained the discriminative patterns using a t-test filter and sparse representation step. We were able to distinguish the young from old cohort with a very high accuracy using only a few voxels of the discriminative patterns (group 1∶98.4%; group 2∶96.4%). The experimental results showed that the selected voxels may be categorized into two components according to the two steps in the proposed method. The first component focuses on the precentral and postcentral gyri, and the caudate nucleus, which play an important role in sensorimotor tasks. The strongest volume reduction with age was observed in these clusters. The second component is mainly distributed over the cerebellum, thalamus, and right inferior frontal gyrus. These regions are not only critical nodes of the sensorimotor circuitry but also the cognitive circuitry although their volume shows a relative resilience against aging. Considering the voxels selection procedure, we suggest that the aging of the sensorimotor and cognitive brain regions identified in this study has a covarying relationship with each other.