2002), and further intensity normalization was conducted. This was followed by white matter segmentation, tessellation of the gray–white matter boundary, and automated RG7204 cost topology correction (Fischl et al. 2001). Then surface deformation following intensity gradients optimally placed the gray/white and gray/cerebrospinal fluid borders at the Inhibitors,research,lifescience,medical location where the greatest shift in intensity defines the transition to the other tissue class (Fischl et al. 2001). Once the cortical models were complete, deformable

procedures performed additional data processing and analysis, including parcellation of the cerebral cortex into 34 conventional gyral-and sulcal-based neuroanatomical regions in each hemisphere (Desikan et al. 2006). This

parcellation method demonstrates diagnostic sensitivity in other diseases (Desikan et al. 2009). Intensity and continuity information from the segmentation and deformation procedures produced representations Inhibitors,research,lifescience,medical of cortical thickness, which were calculated as the closest distance from the gray–white matter boundary to the gray–CSF boundary at each vertex on the tessellated surface (Fischl and Dale 2000). Cortical thickness was used in this study as it accounts for most volumetric changes in prHD (Nopoulos et al. 2010) and is influenced Inhibitors,research,lifescience,medical by genetic factors (Winkler et al. 2010). Statistical analyses We employed the random forest method (Breiman 2001) to identify the relationships between brain morphometric Inhibitors,research,lifescience,medical measures and cognition for several reasons. First, there are a large number of variables (brain regions) and many of them are highly correlated. It is important to include correlated brain regions in the same model, but under the traditional regression framework the

simultaneous inclusion of highly correlated variables can Inhibitors,research,lifescience,medical cause a severe multicollinearity problem and lead to invalid statistical inference. A second issue is that brain regions interact with each other to fulfill a cognitive function. However, for a standard regression analysis, an exhaustive specification of all the interactions among brain regions is near impossible. A third consideration is that it may be overly simplified to assume that all brain regions relate to a cognitive function in a linear fashion. The random forest method is well equipped to handle these challenges. Random forest is an ensemble method that works by Isotretinoin generating a large number of data sets via resampling with replacement from the original data set (bootstrap samples) and making a collective decision (e.g., association) by combining results from the analyses of all resampled data sets. Random forest has a built-in training and testing mechanism to overcome overfitting problems associated with traditional machine learning methods (Smialowski et al. 2010).