Xilin Shen

Groupwise whole-brain parcellation from resting-state fMRI data for network node identification.

In this paper, we present a groupwise graph-theory-based parcellation approach to define nodes for network analysis. The application of network-theory-based analysis to extend the utility of functional MRI has recently received increased attention. Such analyses require first and foremost a reasonable definition of a set of nodes as input to the network analysis. To date many applications have used existing atlases based on cytoarchitecture, task-based fMRI activations, or anatomic delineations. A potential pitfall in using such atlases is that the mean timecourse of a node may not represent any of the constituent timecourses if different functional areas are included within a single node. The proposed approach involves a groupwise optimization that ensures functional homogeneity within each subunit and that these definitions are consistent at the group level. Parcellation reproducibility of each subunit is computed across multiple groups of healthy volunteers and is demonstrated to be high. Issues related to the selection of appropriate number of nodes in the brain are considered. Within typical parameters of fMRI resolution, parcellation results are shown for a total of 100, 200, and 300 subunits. Such parcellations may ultimately serve as a functional atlas for fMRI and as such three atlases at the 100-, 200- and 300-parcellation levels derived from 79 healthy normal volunteers are made freely available online along with tools to interface this atlas with SPM, BioImage Suite and other analysis packages.

A neuromarker of sustained attention from whole-brain functional connectivity

Although attention plays a ubiquitous role in perception and cognition, researchers lack a simple way to measure a persons overall attentional abilities. Because behavioral measures are diverse and difficult to standardize, we pursued a neuromarker of an important aspect of attention, sustained attention, using functional magnetic resonance imaging. To this end, we identified functional brain networks whose strength during a sustained attention task predicted individual differences in performance. Models based on these networks generalized to previously unseen individuals, even predicting performance from resting-state connectivity alone. Furthermore, these same models predicted a clinical measure of attention—symptoms of attention deficit hyperactivity disorder—from resting-state connectivity in an independent sample of children and adolescents. These results demonstrate that whole-brain functional network strength provides a broadly applicable neuromarker of sustained attention.

Graph-Theory Based Parcellation of Functional Subunits in the Brain from Resting-State fMRI data

Resting-state fMRI provides a method to examine the functional network of the brain under spontaneous fluctuations. A number of studies have proposed using resting-state BOLD data to parcellate the brain into functional subunits. In this work, we present two state-of-the-art graph-based partitioning approaches, and investigate their application to the problem of brain network segmentation using resting-state fMRI. The two approaches, the normalized cut (Ncut) and the modularity detection algorithm, are also compared to the Gaussian mixture model (GMM) approach. We show that the Ncut approach performs consistently better than the modularity detection approach, and it also outperforms the GMM approach for in vivo fMRI data. Resting-state fMRI data were acquired from 43 healthy subjects, and the Ncut algorithm was used to parcellate several different cortical regions of interest. The group-wise delineation of the functional subunits based on resting-state fMRI was highly consistent with the parcellation results from two task-based fMRI studies (one with 18 subjects and the other with 20 subjects). The findings suggest that whole-brain parcellation of the cortex using resting-state fMRI is feasible, and that the Ncut algorithm provides the appropriate technique for this task.

A whole-brain voxel based measure of intrinsic connectivity contrast reveals local changes in tissue connectivity with anesthetic without a priori assumptions on thresholds or regions of interest

The analysis of spontaneous fluctuations of functional magnetic resonance imaging (fMRI) signals has recently gained attention as a powerful tool for investigating brain circuits in a non-invasive manner. Correlation-based connectivity analysis investigates the correlations of spontaneous fluctuations of the fMRI signal either between a single seed region of interest (ROI) and the rest of the brain or between multiple ROIs. To do this, a priori knowledge is required for defining the ROI(s) and without such knowledge functional connectivity fMRI cannot be used as an exploratory tool for investigating the functional organization of the brain and its modulation under different conditions. In this work we examine two indices that provide voxel based maps reflecting the intrinsic connectivity contrast (ICC) of individual tissue elements without the need for defining ROIs and hence require no a priori information or assumptions. These voxel based ICC measures can also be used to delineate regions of interest for further functional or network analyses. The indices were applied to the study of sevoflurane anesthesia-induced alterations in intrinsic connectivity. In concordance with previous studies, the results show that sevoflurane affects different brain circuits in a heterogeneous manner. In addition ICC analyses revealed changes in regions not previously identified using conventional ROI connectivity analyses, probably because of an inappropriate choice of the ROI in the earlier studies. This work highlights the importance of such voxel based connectivity methodology.

Detection and Segmentation of Concealed Objects in Terahertz Images

Terahertz imaging makes it possible to acquire images of objects concealed underneath clothing by measuring the radiometric temperatures of different objects on a human subject. The goal of this work is to automatically detect and segment concealed objects in broadband 0.1-1 THz images. Due to the inherent physical properties of passive terahertz imaging and associated hardware, images have poor contrast and low signal to noise ratio. Standard segmentation algorithms are unable to segment or detect concealed objects. Our approach relies on two stages. First, we remove the noise from the image using the anisotropic diffusion algorithm. We then detect the boundaries of the concealed objects. We use a mixture of Gaussian densities to model the distribution of the temperature inside the image. We then evolve curves along the isocontours of the image to identify the concealed objects. We have compared our approach with two state-of-the-art segmentation methods. Both methods fail to identify the concealed objects, while our method accurately detected the objects. In addition, our approach was more accurate than a state-of-the-art supervised image segmentation algorithm that required that the concealed objects be already identified. Our approach is completely unsupervised and could work in real-time on dedicated hardware.

The (in)stability of functional brain network measures across thresholds.

The large-scale organization of the brain has features of complex networks that can be quantified using network measures from graph theory. However, many network measures were designed to be calculated on binary graphs, whereas functional brain organization is typically inferred from a continuous measure of correlations in temporal signal between brain regions. Thresholding is a necessary step to use binary graphs derived from functional connectivity data. However, there is no current consensus on what threshold to use, and network measures and group contrasts may be unstable across thresholds. Nevertheless, whole-brain network analyses are being applied widely with findings typically reported at an arbitrary threshold or range of thresholds. This study sought to evaluate the stability of network measures across thresholds in a large resting state functional connectivity dataset. Network measures were evaluated across absolute (correlation-based) and proportional (sparsity-based) thresholds, and compared between sex and age groups. Overall, network measures were found to be unstable across absolute thresholds. For example, the direction of group differences in a given network measure may change depending on the threshold. Network measures were found to be more stable across proportional thresholds. These results demonstrate that caution should be used when applying thresholds to functional connectivity data and when interpreting results from binary graph models.

Sex differences in normal age trajectories of functional brain networks

Resting‐state functional magnetic resonance image (rs‐fMRI) is increasingly used to study functional brain networks. Nevertheless, variability in these networks due to factors such as sex and aging is not fully understood. This study explored sex differences in normal age trajectories of resting‐state networks (RSNs) using a novel voxel‐wise measure of functional connectivity, the intrinsic connectivity distribution (ICD). Males and females showed differential patterns of changing connectivity in large‐scale RSNs during normal aging from early adulthood to late middle‐age. In some networks, such as the default‐mode network, males and females both showed decreases in connectivity with age, albeit at different rates. In other networks, such as the fronto‐parietal network, males and females showed divergent connectivity trajectories with age. Main effects of sex and age were found in many of the same regions showing sex‐related differences in aging. Finally, these sex differences in aging trajectories were robust to choice of preprocessing strategy, such as global signal regression. Our findings resolve some discrepancies in the literature, especially with respect to the trajectory of connectivity in the default mode, which can be explained by our observed interactions between sex and aging. Overall, results indicate that RSNs show different aging trajectories for males and females. Characterizing effects of sex and age on RSNs are critical first steps in understanding the functional organization of the human brain. Hum Brain Mapp 36:1524–1535, 2015.

Using connectome-based predictive modeling to predict individual behavior from brain connectivity

Neuroimaging is a fast-developing research area in which anatomical and functional images of human brains are collected using techniques such as functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), and electroencephalography (EEG). Technical advances and large-scale data sets have allowed for the development of models capable of predicting individual differences in traits and behavior using brain connectivity measures derived from neuroimaging data. Here, we present connectome-based predictive modeling (CPM), a data-driven protocol for developing predictive models of brain-behavior relationships from connectivity data using cross-validation. This protocol includes the following steps: (i) feature selection, (ii) feature summarization, (iii) model building, and (iv) assessment of prediction significance. We also include suggestions for visualizing the most predictive features (i.e., brain connections). The final result should be a generalizable model that takes brain connectivity data as input and generates predictions of behavioral measures in novel subjects, accounting for a considerable amount of the variance in these measures. It has been demonstrated that the CPM protocol performs as well as or better than many of the existing approaches in brain-behavior prediction. As CPM focuses on linear modeling and a purely data-driven approach, neuroscientists with limited or no experience in machine learning or optimization will find it easy to implement these protocols. Depending on the volume of data to be processed, the protocol can take 10-100 min for model building, 1-48 h for permutation testing, and 10-20 min for visualization of results.

Potential Use and Challenges of Functional Connectivity Mapping in Intractable Epilepsy

This review focuses on the use of resting-state functional magnetic resonance imaging data to assess functional connectivity in the human brain and its application in intractable epilepsy. This approach has the potential to predict outcomes for a given surgical procedure based on the pre-surgical functional organization of the brain. Functional connectivity can also identify cortical regions that are organized differently in epilepsy patients either as a direct function of the disease or through indirect compensatory responses. Functional connectivity mapping may help identify epileptogenic tissue, whether this is a single focal location or a network of seizure-generating tissues. This review covers the basics of connectivity analysis and discusses particular issues associated with analyzing such data. These issues include how to define nodes, as well as differences between connectivity analyses of individual nodes, groups of nodes, and whole-brain assessment at the voxel level. The need for arbitrary thresholds in some connectivity analyses is discussed and a solution to this problem is reviewed. Overall, functional connectivity analysis is becoming an important tool for assessing functional brain organization in epilepsy.

Intrinsic Brain Connectivity Related to Age in Young and Middle Aged Adults

Age-related variations in resting state connectivity of the human brain were examined from young adulthood through middle age. A voxel-based network measure, degree, was used to assess age-related differences in tissue connectivity throughout the brain. Increases in connectivity with age were found in paralimbic cortical and subcortical regions. Decreases in connectivity were found in cortical regions, including visual areas and the default mode network. These findings differ from those of recent developmental studies examining earlier growth trajectories, and are consistent with known changes in cognitive function and emotional processing during mature aging. The results support and extend previous findings that relied on a priori definitions of regions of interest for their analyses. This approach of applying a voxel-based measure to examine the functional connectivity of individual tissue elements over time, without the need for a priori region of interest definitions, provides an important new tool in brain science.