WAVELET-DOMAIN REGRESSION AND PREDICTIVE INFERENCE IN PSYCHIATRIC NEUROIMAGING.

An increasingly important goal of psychiatry is the use of brain imaging data to develop predictive models. Here we present two contributions to statistical methodology for this purpose. First, we propose and compare a set of wavelet-domain procedures for fitting generalized linear models with scalar responses and image predictors: sparse variants of principal component regression and of partial least squares, and the elastic net. Second, we consider assessing the contribution of image predictors over and above available scalar predictors, in particular via permutation tests and an extension of the idea of confounding to the case of functional or image predictors. Using the proposed methods, we assess whether maps of a spontaneous brain activity measure, derived from functional magnetic resonance imaging, can meaningfully predict presence or absence of attention deficit/hyperactivity disorder (ADHD). Our results shed light on the role of confounding in the surprising outcome of the recent ADHD-200 Global Competition, which challenged researchers to develop algorithms for automated image-based diagnosis of the disorder.