Publications

Good cognitive performance requires adherence to rules specific to the task at hand. Patients with neurological disease often make rule violation (RV) errors, but the anatomical basis for RV during cognitive testing remains debated. The present study examined the neuroanatomical correlates of RV errors made on tests of executive functioning in 166 subjects diagnosed with neurodegenerative disease or as neurologically healthy. Specifically, RV errors were voxel-wisely correlated with gray matter volume derived from high-definition magnetic resonance images using voxel-based morphometry implemented in SPM2. Latent variable analysis showed that RV errors tapped a unitary construct separate from repetition errors. This analysis was used to generate factor scores to represent what is common among RV errors across tests. The extracted RV factor scores correlated with tissue loss in the lateral middle and inferior frontal gyri and the caudate nucleus bilaterally. When a more stringent control for global cognitive functioning was applied using Mini Mental State Exam scores, only the correlations with the right lateral prefrontal cortex (PFC) remained significant. These data underscore the importance of right lateral PFC in behavioral monitoring and highlight the potential of RV error assessment for identifying patients with damage to this region.

OBJECTIVE

Subgroups of mild cognitive impairment (MCI) have been proposed, but few studies have investigated the nonamnestic, single-domain subgroup of MCI. The goal of the study was to compare clinical and neuroimaging characteristics of two single-domain MCI subgroups: amnestic MCI and dysexecutive MCI.

METHODS

We compared the cognitive, functional, behavioral, and brain imaging characteristics of patients with amnestic MCI (n = 26), patients with dysexecutive MCI (n = 32), and age- and education-matched control subjects (n = 36) using analysis of variance and chi(2) tests. We used voxel-based morphometry to examine group differences in brain magnetic resonance imaging atrophy patterns.

RESULTS

Patients with dysexecutive MCI had significantly lower scores on the majority of executive function tests, increased behavioral symptoms, and left prefrontal cortex atrophy on magnetic resonance imaging when compared with control subjects. In contrast, patients with amnestic MCI had significantly lower scores on tests of memory and a pattern of atrophy including bilateral hippocampi and entorhinal cortex, right inferior parietal cortex, and posterior cingulate gyrus when compared with control subjects.

INTERPRETATION

Overall, the clinical and neuroimaging findings provide support for two distinct single-domain subgroups of MCI, one involving executive function and the other involving memory. The brain imaging differences suggest that the two MCI subgroups have distinct patterns of brain atrophy.