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

Connectivity analyses and computational modeling of human brain function from fMRI data frequently require the specification of regions of interests (ROIs). Several analyses have relied on atlases derived from anatomical or cyto-architectonic boundaries to specify these ROIs, yet the suitability of atlases for resting state functional connectivity (FC) studies has yet to be established. This article introduces a data-driven method for generating an ROI atlas by parcellating whole brain resting-state fMRI data into spatially coherent regions of homogeneous FC. Several clustering statistics are used to compare methodological trade-offs as well as determine an adequate number of clusters. Additionally, we evaluate the suitability of the parcellation atlas against four ROI atlases (Talairach and Tournoux, Harvard-Oxford, Eickoff-Zilles, and Automatic Anatomical Labeling) and a random parcellation approach. The evaluated anatomical atlases exhibit poor ROI homogeneity and do not accurately reproduce FC patterns present at the voxel scale. In general, the proposed functional and random parcellations perform equivalently for most of the metrics evaluated. ROI size and hence the number of ROIs in a parcellation had the greatest impact on their suitability for FC analysis. With 200 or fewer ROIs, the resulting parcellations consist of ROIs with anatomic homology, and thus offer increased interpretability. Parcellation results containing higher numbers of ROIs (600 or 1,000) most accurately represent FC patterns present at the voxel scale and are preferable when interpretability can be sacrificed for accuracy. The resulting atlases and clustering software have been made publicly available at: http://www.nitrc.org/projects/cluster_roi/. Copyright © 2011 Wiley Periodicals, Inc.

The increase in spatiotemporal resolution of neuroimaging devices is accompanied by a trend towards more powerful multivariate analysis methods. Often it is desired to interpret the outcome of these methods with respect to the cognitive processes under study. Here we discuss which methods allow for such interpretations, and provide guidelines for choosing an appropriate analysis for a given experimental goal: For a surgeon who needs to decide where to remove brain tissue it is most important to determine the origin of cognitive functions and associated neural processes. In contrast, when communicating with paralyzed or comatose patients via brain-computer interfaces, it is most important to accurately extract the neural processes specific to a certain mental state. These equally important but complementary objectives require different analysis methods. Determining the origin of neural processes in time or space from the parameters of a data-driven model requires what we call a forward model of the data; such a model explains how the measured data was generated from the neural sources. Examples are general linear models (GLMs). Methods for the extraction of neural information from data can be considered as backward models, as they attempt to reverse the data generating process. Examples are multivariate classifiers. Here we demonstrate that the parameters of forward models are neurophysiologically interpretable in the sense that significant nonzero weights are only observed at channels the activity of which is related to the brain process under study. In contrast, the interpretation of backward model parameters can lead to wrong conclusions regarding the spatial or temporal origin of the neural signals of interest, since significant nonzero weights may also be observed at channels the activity of which is statistically independent of the brain process under study. As a remedy for the linear case, we propose a procedure for transforming backward models into forward models. This procedure enables the neurophysiological interpretation of the parameters of linear backward models. We hope that this work raises awareness for an often encountered problem and provides a theoretical basis for conducting better interpretable multivariate neuroimaging analyses. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

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. Copyright © 2013 Elsevier Inc. All rights reserved.