Computational and Mathematical Methods in Medicine
Volume 2012 (2012), Article ID 967380, 14 pages
http://dx.doi.org/10.1155/2012/967380
Research Article

A Computationally Efficient, Exploratory Approach to Brain Connectivity Incorporating False Discovery Rate Control, A Priori Knowledge, and Group Inference

Aiping Liu,1 Junning Li,2 Z. Jane Wang,1 and Martin J. McKeown1,3

1Department of Electrical and Computer Engineering, University of British Columbia, Vancouver, BC, Canada V6T 1Z4
2Laboratory of Neuro Imaging, Department of Neurology, UCLA School of Medicine, Los Angeles, CA 90095, USA
3Division of Neurology, Department of Medicine and Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada V5Z 1M9

Received 18 March 2012; Revised 6 July 2012; Accepted 10 July 2012

Academic Editor: Tianzi Jiang

Copyright © 2012 Aiping Liu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Graphical models appear well suited for inferring brain connectivity from fMRI data, as they can distinguish between direct and indirect brain connectivity. Nevertheless, biological interpretation requires not only that the multivariate time series are adequately modeled, but also that there is accurate error-control of the inferred edges. The PCfdr algorithm, which was developed by Li and Wang, was to provide a computationally efficient means to control the false discovery rate (FDR) of computed edges asymptotically. The original PCfdr algorithm was unable to accommodate a priori information about connectivity and was designed to infer connectivity from a single subject rather than a group of subjects. Here we extend the original PCfdr algorithm and propose a multisubject, error-rate-controlled brain connectivity modeling approach that allows incorporation of prior knowledge of connectivity. In simulations, we show that the two proposed extensions can still control the FDR around or below a specified threshold. When the proposed approach is applied to fMRI data in a Parkinson’s disease study, we find robust group evidence of the disease-related changes, the compensatory changes, and the normalizing effect of L-dopa medication. The proposed method provides a robust, accurate, and practical method for the assessment of brain connectivity patterns from functional neuroimaging data.