In this regard, it is JNK inhibitor in vivo important to identify the brain centers that govern core cognitive functions, as the suitability of a cognitive measure will likely depend on the target of a treatment intervention. The brain mechanisms of cognitive impairment in prHD are not well understood partly due to the dearth of structural imaging investigations into neurocognitive relationships. Despite progressive changes in the striatum and in cortical gray and white matter that begin decades before a manifest

diagnosis (Nopoulos et al. 2010; Paulsen et al. 2010; Aylward et al. 2011; Tabrizi Inhibitors,research,lifescience,medical et al. 2011, 2012), much less is known about how they relate to functioning in different cognitive domains. Several studies of prHD have Inhibitors,research,lifescience,medical reported that striatal volume (Campodonico et al. 1998; Jurgens et al. 2008; Paulsen et al. 2010; Papp et al. 2013; Wolf et al. 2013) and/or white matter volume (Paulsen et al. 2010; Papp et al. 2013) correlate with measures of executive functioning including the Inhibitors,research,lifescience,medical Symbol Digits Modality Test (SDMT), Stroop Interference, Verbal Fluency, the Trial Making Test Part B, and the Towers Task. Yet few studies of prHD have

investigated whether cortical gray matter morphometry correlates in meaningful ways with functioning in different cognitive domains. In an early study of 15 prHD individuals Inhibitors,research,lifescience,medical that used whole-brain voxel-based morphometry (VBM) (Rosas et al. 2005), linear regression analyses

revealed that Verbal Fluency, Stroop Interference, and SDMT performances correlated with cortical thinning in some spatially different regions, suggesting that structural changes were functionally meaningful. Yet a recent study of 20 prHD individuals found no statistically significant relationships between cortical morphometry and cognitive functioning on tests of alertness, divided attention, verbal and spatial working memory, inhibition, or executive dysfunction Inhibitors,research,lifescience,medical (Wisconsin Card Sorting Test, WCST), irrespective of the structural magnetic Tryptophan synthase resonance imaging (sMRI) method employed (i.e., VBM and cortical surface modeling) (Wolf et al. 2013). These discrepant findings may relate to the small sample sizes, which is problematic given the heterogeneity of symptoms and disease progression in prHD. Other studies of large combined samples of prHD and manifest HD have revealed relationships between cortical thinning and cognition (e.g., timing, visuomotor integration, emotion recognition) (Bechtel et al. 2010; Say et al. 2011; Scahill et al. 2013). However, the results do not address the neurocognitive relationships in the premanifest period, wherein structural changes in the brain may exhibit more regionally specific relationships with different cognitive functions rather than potentially relate more to global neurodegeneration.