Scaled subprofile modeling of resting state imaging data in Parkinson's disease: methodological issues.

Consistent functional brain abnormalities in Parkinson's disease (PD) are difficult to pinpoint because differences from the normal state are often subtle. In this regard, the application of multivariate methods of analysis has been successful but not devoid of misinterpretation and controversy. The Scaled Subprofile Model (SSM), a principal components analysis (PCA)-based spatial covariance method, has yielded critical information regarding the characteristic abnormalities of functional brain organization that underlie PD and other neurodegenerative disorders. However, the relevance of disease-related spatial covariance patterns (metabolic brain networks) and the most effective methods for their derivation has been a subject of debate. We address these issues here and discuss the inherent advantages of proper application as well as the effects of the misapplication of this methodology. We show that ratio pre-normalization using the mean global metabolic rate (GMR) or regional values from a "reference" brain region (e.g. cerebellum) that may be required in univariate analytical approaches is obviated in SSM. We discuss deviations of the methodology that may yield erroneous or confounding factors.