Functional brain networks before the onset of psychosis : a prospective fMRI study with graph theoretical analysis

Individuals with an at-risk mental state (ARMS) have a risk of developing a psychotic disorder significantly greater than the general population. However, it is not currently possible to predict which ARMS individuals will develop psychosis from clinical assessment alone. Comparison of ARMS subjects who do, and do not, develop psychosis can reveal which factors are critical for the onset of illness. In the present study, 37 patients with an ARMS were followed clinically at least 24 months subsequent to initial referral. Functional MRI data were collected at the beginning of the follow-up period during performance of an executive task known to recruit frontal lobe networks and to be impaired in psychosis. Graph theoretical analysis was used to compare the organization of a functional brain network in ARMS patients who developed a psychotic disorder following the scan (ARMS-T) to those who did not become ill during the same follow-up period (ARMS-NT) and aged-matched controls. The global properties of each group's representative network were studied (density, efficiency, global average path length) as well as regionally-specific contributions of network nodes to the organization of the system (degree, farness-centrality, betweenness-centrality). We focused our analysis on the dorsal anterior cingulate cortex (ACC), a region known to support executive function that is structurally and functionally impaired in ARMS patients. In the absence of between-group differences in global network organization, we report a significant reduction in the topological centrality of the ACC in the ARMS-T group relative to both ARMS-NT and controls. These results provide evidence that abnormalities in the functional organization of the brain predate the onset of psychosis, and suggest that loss of ACC topological centrality is a potential biomarker for transition to psychosis

Effects of chronic sleep restriction on the brain functional network, as revealed by graph theory

Sleep is a complex and dynamic process for maintaining homeostasis, and a lack of sleep can disrupt whole-body functioning. No organ is as vulnerable to the loss of sleep as the brain. Accordingly, we examined a set of task-based functional magnetic resonance imaging (fMRI) data by using graph theory to assess brain topological changes in subjects in a state of chronic sleep restriction, and then identified diurnal variability in the graph-theoretic measures. Task-based fMRI data were collected in a 1.5T MR scanner from the same participants on two days: after a week of fully restorative sleep and after a week with 35% sleep curtailment. Each day included four scanning sessions throughout the day (at approximately 10:00 AM, 2:00 PM, 6:00 PM, and 10:00 PM). A modified spatial cueing task was applied to evaluate sustained attention. After sleep restriction, the characteristic path length significantly increased at all measurement times, and small-worldness significantly decreased. Assortativity, a measure of network fault tolerance, diminished over the course of the day in both conditions. Local graph measures were altered primarily across the limbic system (particularly in the hippocampus, parahippocampal gyrus, and amygdala), default mode network, and visual network

Disrupted Small-World Brain Networks in Moderate Alzheimer's Disease: A Resting-State fMRI Study

The small-world organization has been hypothesized to reflect a balance between local processing and global integration in the human brain. Previous multimodal imaging studies have consistently demonstrated that the topological architecture of the brain network is disrupted in Alzheimer's disease (AD). However, these studies have reported inconsistent results regarding the topological properties of brain alterations in AD. One potential explanation for these inconsistent results lies with the diverse homogeneity and distinct progressive stages of the AD involved in these studies, which are thought to be critical factors that might affect the results. We investigated the topological properties of brain functional networks derived from resting functional magnetic resonance imaging (fMRI) of carefully selected moderate AD patients and normal controls (NCs). Our results showed that the topological properties were found to be disrupted in AD patients, which showing increased local efficiency but decreased global efficiency. We found that the altered brain regions are mainly located in the default mode network, the temporal lobe and certain subcortical regions that are closely associated with the neuropathological changes in AD. Of note, our exploratory study revealed that the ApoE genotype modulates brain network properties, especially in AD patients

Graph theoretical framework of brain networks in multiple sclerosis: a review of concepts

Network science provides powerful access to essential organizational principles of the human brain. It has been applied in combination with graph theory to characterize brain connectivity patterns. In multiple sclerosis (MS), analysis of the brain networks derived from either structural or functional imaging provides new insights into pathological processes within the gray and white matter. Beyond focal lesions and diffuse tissue damage, network connectivity patterns could be important for closely tracking and predicting the disease course. In this review, we describe concepts of graph theory, highlight novel issues of tissue reorganization in acute and chronic neuroinflammation and address pitfalls with regard to network analysis in MS patients. We further provide an outline of functional and structural connectivity patterns observed in MS, spanning from disconnection and disruption on one hand to adaptation and compensation on the other. Moreover, we link network changes and their relation to clinical disability based on the current literature. Finally, we discuss the perspective of network science in MS for future research and postulate its role in the clinical framework

SEARCHING NEUROIMAGING BIOMARKERS IN MENTAL DISORDERS WITH GRAPH AND MULTIMODAL FUSION ANALYSIS OF FUNCTIONAL CONNECTIVITY

Mental disorders such as schizophrenia (SZ), bipolar (BD), and major depression disorders (MDD) can cause severe symptoms and life disruption. They share some symptoms, which can pose a major clinical challenge to their differentiation. Objective biomarkers based on neuroimaging may help to improve diagnostic accuracy and facilitate optimal treatment for patients. Over the last decades, non-invasive in-vivo neuroimaging techniques such as magnetic resonance imaging (MRI) have been increasingly applied to measure structure and function in human brains. With functional MRI (fMRI) or structural MRI (sMRI), studies have identified neurophysiological deficits in patients’ brain from different perspective. Functional connectivity (FC) analysis is an approach that measures functional integration in brains. By assessing the temporal coherence of the hemodynamic activity among brain regions, FC is considered capable of characterizing the large-scale integrity of neural activity. In this work, we present two data analysis frameworks for biomarker detection on brain imaging with FC, 1) graph analysis of FC and 2) multimodal fusion analysis, to better understand the human brain. Graph analysis reveals the interaction among brain regions based on graph theory, while the multimodal fusion framework enables us to utilize the strength of different imaging modalities through joint analysis. Four applications related to FC using these frameworks were developed. First, FC was estimated using a model-based approach, and revealed altered the small-world network structure in SZ. Secondly, we applied graph analysis on functional network connectivity (FNC) to differentiate BD and MDD during resting-state. Thirdly, two functional measures, FNC and fractional amplitude of low frequency fluctuations (fALFF), were spatially overlaid to compare the FC and spatial alterations in SZ. And finally, we utilized a multimodal fusion analysis framework, multi-set canonical correlation analysis + joint independent component analysis (mCCA+jICA) to link functional and structural abnormalities in BD and MDD. We also evaluated the accuracy of predictive diagnosis through classifiers generated on the selected features. In summary, via the two frameworks, our work has made several contributions to advance FC analysis, which improves our understanding of underlying brain function and structure, and our findings may be ultimately useful for the development of biomarkers of mental disease

Attention Performance Measured by Attention Network Test Is Correlated with Global and Regional Efficiency of Structural Brain Networks

Functional neuroimaging studies have indicated the involvement of separate brain areas in three distinct attention systems: alerting, orienting and executive control (EC). However, the structural correlates underlying attention remains unexplored. Here, we utilized graph theory to examine the neuroanatomical substrates of the three attention systems measured by attention network test (ANT) in 65 healthy subjects. White matter connectivity, assessed with DTI deterministic tractography was modeled as a structural network comprising 90 nodes defined by the Automated Anatomical Labeling (AAL) template. Linear regression analyses were conducted to explore the relationship between topological parameters and the three attentional effects. We found a significant positive correlation between EC function and global efficiency of the whole brain network. At the regional level, node-specific correlations were discovered between regional efficiency and all three ANT components, including dorsolateral superior frontal gyrus, thalamus and parahippocampal gyrus for EC, thalamus and inferior parietal gyrus for alerting, and paracentral lobule and inferior occipital gyrus for orienting. Our findings highlight the fundamental architecture of interregional structural connectivity involved in attention and could provide new insights into the anatomical basis underlying human behavior

Neural correlates of post-traumatic brain injury (TBI) attention deficits in children

Traumatic brain injury (TBI) in children is a major public health concern worldwide. Attention deficits are among the most common neurocognitive and behavioral consequences in children post-TBI which have significant negative impacts on their educational and social outcomes and compromise the quality of their lives. However, there is a paucity of evidence to guide the optimal treatment strategies of attention deficit related symptoms in children post-TBI due to the lack of understanding regarding its neurobiological substrate. Thus, it is critical to understand the neural mechanisms associated with TBI-induced attention deficits in children so that more refined and tailored strategies can be developed for diagnoses and long-term treatments and interventions. This dissertation is the first study to investigate neurobiological substrates associated with post-TBI attention deficits in children using both anatomical and functional neuroimaging data. The goals of this project are to discover the quantitatively measurable markers utilizing diffusion tensor imaging (DTI), structural magnetic resonance imaging (MRI), and functional MRI (fMRI) techniques, and to further identify the most robust neuroimaging features in predicting severe post-TBI attention deficits in children, by utilizing machine learning and deep learning techniques. A total of 53 children with TBI and 55 controls from age 9 to 17 are recruited. The results show that the systems-level topological properties in left frontal regions, parietal regions, and medial occipitotemporal regions in structural and functional brain network are significantly associated with inattentive and/or hyperactive/impulsive symptoms in children post-TBI. Semi-supervised deep learning modeling further confirms the significant contributions of these brain features in the prediction of elevated attention deficits in children post-TBI. The findings of this project provide valuable foundations for future research on developing neural markers for TBI-induced attention deficits in children, which may significantly assist the development of more effective and individualized diagnostic and treatment strategies

Effect of rs1344706 in the ZNF804A gene on the brain network.

ZNF804A rs1344706 (A/C) was the first SNP that reached genome-wide significance for schizophrenia. Recent studies have linked rs1344706 to functional connectivity among specific brain regions. However, no study thus far has examined the role of this SNP in the entire functional connectome. In this study, we used degree centrality to test the role of rs1344706 in the whole-brain voxel-wise functional connectome during the resting state. 52 schizophrenia patients and 128 healthy controls were included in the final analysis. In our whole-brain analysis, we found a significant interaction effect of genotype × diagnosis at the precuneus (PCU) (cluster size = 52 voxels, peak voxel MNI coordinates: x = 9, y = - 69, z = 63, F = 32.57, FWE corrected P < 0.001). When we subdivided the degree centrality network according to anatomical distance, the whole-brain analysis also found a significant interaction effect of genotype × diagnosis at the PCU with the same peak in the short-range degree centrality network (cluster size = 72 voxels, F = 37.29, FWE corrected P < 0.001). No significant result was found in the long-range degree centrality network. Our results elucidated the contribution of rs1344706 to functional connectivity within the brain network, and may have important implications for our understanding of this risk gene's role in functional dysconnectivity in schizophrenia