The relationship between long-term blood pressure variability and cortical thickness in older adults.

High blood pressure variability (BPV) is a risk factor for cognitive decline and dementia, but its association with cortical thickness is not well understood. Here we use a topographical approach, to assess links between long-term BPV and cortical thickness in 478 (54% men at baseline) community dwelling older adults (70-88 years) from the ASPirin in Reducing Events in the Elderly NEURO sub-study. BPV was measured as average real variability, based on annual visits across three years. Higher diastolic BPV was significantly associated with reduced cortical thickness in multiple areas, including temporal (banks of the superior temporal sulcus), parietal (supramarginal gyrus, post-central gyrus), and posterior frontal areas (pre-central gyrus, caudal middle frontal gyrus), while controlling for mean BP. Higher diastolic BPV was associated with faster progression of cortical thinning across the three years. Diastolic BPV is an important predictor of cortical thickness, and trajectory of cortical thickness, independent of mean blood pressure. This finding suggests an important biological link in the relationship between BPV and cognitive decline in older age.

The spatial and temporal dynamics of anticipatory preparation and response inhibition in task-switching.

We investigated ERP and fMRI correlates of anticipatory preparation and response inhibition in a cued task-switching paradigm with informatively cued, non-informatively cued and no-go trials. Cue-locked ERPs showed evidence for a multicomponent preparation process. An early cue-locked differential positivity was larger for informative vs. non-informative cues and its amplitude correlated with differential activity for informatively vs. non-informatively cued trials in the dorsolateral prefrontal cortex (DLPFC), consistent with a goal activation process. A later differential positivity was larger for informatively cued switch vs. repeat trials and its amplitude correlated with informatively cued switch vs. repeat activity in the posterior parietal cortex (PPC), compatible with a category-response (C-R) rule activation process. No-go trials elicited a frontal P3, whose amplitude was negatively correlated with activity in the ventrolateral prefrontal cortex (VLPFC) and basal ganglia motor network, suggesting that a network responsible for response execution was inhibited in the course of a no-go trial. These findings indicate that anticipatory preparation in task-switching is comprised of at least two processes: goal activation and C-R rule activation. They also support a functional dissociation between DLPFC and VLPFC, with the former involved in top-down biasing and the latter involved in response inhibition.

Memantine, an NMDA receptor antagonist, differentially influences Go/No-Go performance and fMRI activity in individuals with and without a family history of alcoholism.

RATIONALE: Individuals with a family history of alcoholism (family history positive [FHP]) show higher alcoholism rates and are more impulsive than those without such a family history (family history negative [FHN]), possibly due to altered N-methyl-D-aspartate (NMDA) receptor function. OBJECTIVES: We investigated whether memantine, an NMDA receptor antagonist, differentially influences impulsivity measures and Go/No-Go behavior and fMRI activity in matched FHP and FHN individuals. METHODS: On separate days, participants received a single dose of 40 mg memantine or identical-appearing placebo. RESULTS: No group performance differences were observed on placebo for Go correct hit or No-Go false alarm reaction time on the Go/No-Go task. During fMRI, right cingulate activation differed for FHP vs. FHN subjects during No-Go correct rejects. Memantine had attenuated effects in FHP vs. FHN subjects: For No-Go false alarms, memantine was associated with limited reduction in subcortical, cingulate, and temporal regions in FHP subjects and reduced activity in fronto-striatal-parietal networks in FHN subjects. For No-Go correct rejects, memantine (relative to placebo) reduced activity in left cingulate and caudate in FHP but not FHN subjects. CONCLUSIONS: Lower sensitivity to the effects of memantine in FHP subjects is consistent with greater NMDA receptor function in this group.

Genetic influences of cortical gray matter in language-related regions in healthy controls and schizophrenia.

Individuals with schizophrenia show a broad range of language impairments, including reading difficulties. A recent structural MRI (sMRI) study linked these difficulties to structural abnormalities in language-related regions (Leonard et al., 2008). Similar regions have been implicated in primary reading disability (RD). Major hypotheses of RD implicate abnormal embryonic neuronal migration in the cortex, and genetic linkage and association studies have identified a number of candidate RD genes that are associated with neuronal migration (Paracchini et al., 2007). Interestingly, evidence suggests at least some individuals with schizophrenia also show impaired neuronal migration in the cortex (Akbarian et al., 1996). Thus the aim of this study was to examine the link between RD-related genes and gray matter volumes in healthy controls and schizophrenia. We used parallel independent component analysis (parallel-ICA) to examine the relationship between gray matter volumes extracted using voxel-based morphometry (VBM) and 16 single nucleotide polymorphisms (SNPs) spanning FOXP2 and four RD-related genes, DCDC2, DYX1C1, KIAA0319 and TTRAP. Parallel-ICA identified five sMRI-SNP relationships. Superior and inferior cerebellar networks were related to DYX1C1 and DCDC2/KIAA0319 respectively in both groups. The superior prefrontal, temporal and occipital networks were positively related to DCDC2 in the schizophrenia, but not the control group. The identified networks closely correspond to the known distribution of language processes in the cortex. Thus, reading and language difficulties in schizophrenia may be related to distributed cortical structural abnormalities associated with RD-related genes.

Compensatory mechanisms underlie intact task-switching performance in schizophrenia.

Individuals with schizophrenia tend to perform poorly on many measures of cognitive control. However, recent task-switching studies suggest that they show intact task-switching performance, despite the fact that the regions involved in task-switching are known to be structurally and functionally impaired in the disorder. Behavioral, event-related potential (ERP) and functional magnetic resonance imaging (fMRI) measures were used to compare the temporal and spatial dynamics of task-switching performance in individuals with schizophrenia and controls. Consistent with previous studies, reaction time (RT) switch cost and its reduction with anticipatory preparation did not differ between groups. There were also no group differences on cue-locked ERP components associated with anticipatory preparation processes. However, both stimulus- and response-locked ERPs were significantly disrupted in schizophrenia, suggesting difficulty with task-set implementation. fMRI analyses indicated that individuals with schizophrenia showed hyperactivity in the dorsolateral prefrontal cortex and posterior parietal cortex. RT-fMRI and ERP-fMRI associations suggested that individuals with schizophrenia employ compensatory mechanisms to overcome difficulties in task-set implementation and thereby achieve the same behavioral outcomes as controls.