Visuospatial and Attentional Abilities Predict Driving Simulator Performance Among Older HIV-infected Adults.

OBJECTIVES: To examine the effects of aging and neuropsychological (NP) impairment on driving simulator performance within a human immunodeficiency virus (HIV)-infected cohort. METHODS: Participants included 79 HIV-infected adults (n = 58 > age 50, n = 21 ≤ 40) who completed a NP battery and a personnel computer-based driving simulator task. Outcome variables included total completion time (time) and number of city blocks to complete the task (blocks). RESULTS: Compared to the younger group, the older group was less efficient in their route finding (blocks over optimum: 25.9 [20.1] vs 14.4 [16.9]; P = .02) and took longer to complete the task (time: 1297.6 [577.6] vs 804.4 [458.5] seconds; P = .001). Regression models within the older adult group indicated that visuospatial abilities (blocks: b = -0.40, P <.001; time: b = -0.40, P = .001) and attention (blocks: b = -0.49, P = .001; time: b = -0.42, P = .006) independently predicted simulator performance. The NP-impaired group performed more poorly on both time and blocks, compared to the NP normal group. CONCLUSIONS: Older HIV-infected adults may be at risk of driving-related functional compromise secondary to HIV-associated neurocognitive decline.

Relative shift in activity from medial to lateral frontal cortex during internally versus externally guided word generation.

Goldberg (1985) hypothesized that as language output changes from internally to externally guided production, activity shifts from supplementary motor area (SMA) to lateral premotor areas, including Broca's area. To test this hypothesis, 15 right-handed native English speakers performed three word generation tasks varying in the amount of internal guidance and a repetition task during functional magnetic resonance imaging (fMRI). Volumes of significant activity for each task versus a resting state were derived using voxel-by-voxel repeated-measures t tests (p <.001) across subjects. Changes in the size of activity volumes for left medial frontal regions (SMA and pre-SMA/BA 32) versus left lateral frontal regions (Broca's area, inferior frontal sulcus) were assessed as internal guidance of word generation decreased and external guidance increased. Comparing SMA to Broca's area, Goldberg's hypothesis was not verified. However, pre-SMA/BA 32 activity volumes decreased significantly and inferior frontal sulcus activity volumes increased significantly as word generation tasks moved from internally to externally guided.

Left-hemisphere processing of emotional connotation during word generation.

Areas of the brain's left hemisphere involved in retrieving words with emotional connotations were studied with fMRI. Participants silently generated words from different semantic categories which evoked either words with emotional connotations or emotionally neutral words. Participants repeated emotionally neutral words as a control task. Compared with generation of emotionally neutral words, generation of words with emotional connotations engaged cortices near the left frontal and temporal poles which are connected to the limbic system. Thus, emotional connotations of words are processed in or near cortices with access to emotional experience.

Activity in the paracingulate and cingulate sulci during word generation: an fMRI study of functional anatomy.

The supracallosal medial frontal cortex can be divided into three functional domains: a ventral region with connections to the limbic system, an anterior dorsal region with connections to lateral prefrontal systems, and a posterior dorsal region with connections to lateral motor systems. Lesion and functional imaging studies implicate this medial frontal cortex in speech and language generation. The current functional magnetic resonance imaging (fMRI) study of word generation was designed to determine which of these three functional domains was substantially involved by mapping individual subjects' functional activity onto structural images of their left medial frontal cortex. Of 28 neurologically normal right-handed participants, 21 demonstrated a prominent paracingu- late sulcus (PCS), which lies in the anterior dorsal region with connections to lateral prefrontal systems. Activity increases for word generation centered in the PCS in 18 of these 21 cases. The posterior dorsal region also demonstrated significant activity in a majority of participants (16/28 cases). Activity rarely extended into the cingulate sulcus (CS) (3/21 cases) when there was a prominent PCS. If there was no prominent PCS, however, activity did extend into the CS (6/7 cases). In no case was activity present on the crest of the cingulate gyrus, which is heavily connected to the limbic system. Thus, current findings suggest that medial frontal activity during word generation reflects cognitive and motor rather than limbic system participation. The current study demonstrates that suitably designed fMRI studies can be used to determine the functional significance of anatomic variants in human cortex.

Distinct cognitive profiles of cortical and subcortical dementia in advanced illness.

We administered the Mattis Dementia Rating Scale (DRS) to 120 patients to evaluate the effect of dementia severity on distinct cognitive profiles. Sixty patients with Huntington's disease (HD) and 60 patients with Alzheimer's disease (AD) were separated by dementia severity into three groups: mildly demented (DRS mean total = 129), moderately demented (DRS mean total = 117), and severely demented (DRS mean total = 102). At all levels of dementia severity, HD patients demonstrated greater impairment than AD patients on the Initiation/Perseveration subscale, whereas AD patients demonstrated greater impairment than HD patients on the Memory subscale. At moderate and severe levels of dementia, HD patients demonstrated an additional impairment in constructional praxis. These profile differences were independent of dementia severity and continued to differentiate between so-called cortical and subcortical dementias in later stages of dementia severity.

The nature of learning and memory impairments in schizophrenia.

The California Verbal Learning Test was used to characterize the learning and memory impairment in schizophrenia (SC) and to evaluate potential clinical and demographic factors associated with this impairment. SC patients (n = 175) performed worse than normal comparison (NC) subjects (n = 229) on all learning, recall, and recognition memory measures. The most important clinical correlates of these impairments were earlier age of onset, more negative symptoms, and greater anticholinergic medication dosage. SC patients showed a prominent retrieval deficit as indicated by disproportionate improvement when tested in a recognition, rather than a free recall, format. A residual impairment seen with recognition testing suggests a mild encoding deficit as well. In contrast, the relative absence of a storage deficit is suggested by the lack of rapid forgetting. Using a discriminant function analysis that differentiates cortical dementia [i.e., Alzheimer's disease (AD)], subcortical dementia [i.e., Huntington's disease (HD)], and normals, it was found that 50% of the SC patients were classified as having a subcortical memory profile and 35% were classified as having a normal profile, whereas only 15% were classified as having a cortical memory profile. Although these findings reflect the clinical heterogeneity often found in SC, results suggest that most SC patients demonstrate a pattern of learning and memory impairments that resembles the pattern seen in patients with primary subcortical (specifically striatal) pathology.