Moreover, it is reasonable to infer that the structure–function relationships identified by our study are more expressed as disease burden advances. However, longitudinal studies are needed to directly evaluate this supposition. Our results build upon reports of cognitive-sMRI associations in combined samples of prHD and HD individuals (Bechtel et al. 2010; Say et al. 2011; Scahill et al. 2013) by elucidating sMRI correlates of Inhibitors,research,lifescience,medical cognitive functioning in different domains that are specific to the premanifest period. One notable finding was that attention and information processing speed, as measured

by the SDMT, was uniquely associated with thickness of both the motor (precentral gyrus) and sensory Inhibitors,research,lifescience,medical (postcentral gyrus) cortices and bilateral RO4929097 clinical trial putamen volume. In fact, the bilateral putamen and right precentral gyrus were highly ranked correlates of performance. These results are compatible with the stronger sensorimotor component of the SDMT relative to most other cognitive measures except timing,

which was also associated with sensory cortex thickness. The results also comport with the correlation Inhibitors,research,lifescience,medical of motor measures, such as maximum tapping speed (Bechtel et al. 2010) and visuomotor integration (Say et al. 2011), with sensorimotor cortex thinning in combined samples of prHD and HD participants, and the correlation of putamen, but not caudate volume, with SDMT performance in prHD (Jurgens et al. 2008). SDMT performance also depends on the capacity to selectively attend to and integrate symbol–digit pairs. This is consistent with its relationship to thickness in mostly right PFC executive-control Inhibitors,research,lifescience,medical centers and in an articulatory/semantic Inhibitors,research,lifescience,medical processing center (bilateral superior temporal cortex), which was also a highly ranked correlate of performance, perhaps because it assists in integrating symbol–digit pairs. A distinctly different

regional pattern of sMRI variables was associated with Rutecarpine letter-number sequencing, which emphasizes executive components of working memory (i.e., manipulation of information) more so than the other tests. Performance was associated with thinning in elements of an executive working memory network, including the inferior parietal cortex and bilateral rostral PFC, which is thought to be engaged by more abstract or complex executive processes than caudal PFC (Badre 2008). Unlike the other cognitive domains, the highest ranked cortical correlates of performance were the right rostral middle-frontal cortex and the right lateral occipital and middle-temporal cortices, which by way of interactions with the PFC, selectively enhance the processing and maintenance of information in working memory (Lee and D’Esposito 2012).