Filtering and storage working memory networks in younger and older age.

INTRODUCTION: Working memory (WM) is a multi-component model that among others involves the two processes of filtering and storage. The first reflects the necessity to inhibit irrelevant information from entering memory, whereas the latter refers to the active maintenance of object representations in memory. In this study, we aimed at a) redefining the neuronal networks sustaining filtering and storage within visual working memory by avoiding shortcomings of prior studies, and b) assessing age-related changes in these networks. METHODS: We designed a new paradigm that strictly controlled for perceptual load by presenting the same number of stimuli in each of three conditions. We calculated fMRI contrasts between a baseline condition (low filter and low storage load) and conditions that posed high demands on filtering and storage, respectively, in large samples of younger (n = 40) and elder (n = 38) participants. RESULTS: Our approach of comparing contrasts between groups revealed more extensive filter and storage WM networks than previous studies. In the younger group, filtering involved the bilateral insulae, the right occipital cortex, the right brainstem, and the right cerebellum. In the elder group, filtering was associated with the bilateral insulae, right precuneus, and bilateral ventromedial prefrontal cortex. An extensive neuronal network was also found during storage of information in the bilateral posterior parietal cortex, the left ventromedial prefrontal cortex, and the right precuneus in the younger participants. In addition to these brain regions, elder participants recruited the bilateral ventral prefrontal cortex, the superior, middle and inferior and temporal cortex, the left cingulum and the bilateral parahippocampal cortex. CONCLUSIONS: In general, elder participants recruited more brain regions in comparison to younger participants to reach similar accuracy levels. Furthermore, in elder participants one brain region emerged in both contrasts, namely the left ventromedial prefrontal cortex. Hence, elder participants seem to routinely recruit this brain region in demanding tasks, irrespective of whether filtering or storing is challenged.

Subfield-specific loss of hippocampal N-acetyl aspartate in temporal lobe epilepsy.

PURPOSE: In patients with mesial temporal lobe epilepsy (MTLE) it remains an unresolved issue whether the interictal decrease in N-acetyl aspartate (NAA) detected by proton magnetic resonance spectroscopy ((1)H-MRS) reflects the epilepsy-associated loss of hippocampal pyramidal neurons or metabolic dysfunction. METHODS: To address this problem, we applied high-resolution (1)H-MRS at 14.1 Tesla to measure metabolite concentrations in ex vivo tissue slices from three hippocampal subfields (CA1, CA3, dentate gyrus) as well as from the parahippocampal region of 12 patients with MTLE. RESULTS: In contrast to four patients with lesion-caused MTLE, we found a large variance of NAA concentrations in the individual hippocampal regions of patients with Ammon's horn sclerosis (AHS). Specifically, in subfield CA3 of AHS patients despite of a moderate preservation of neuronal cell densities the concentration of NAA was significantly lowered, while the concentrations of lactate, glucose, and succinate were elevated. We suggest that these subfield-specific alterations of metabolite concentrations in AHS are very likely caused by impairment of mitochondrial function and not related to neuronal cell loss. CONCLUSIONS: A subfield-specific impairment of energy metabolism is the probable cause for lowered NAA concentrations in sclerotic hippocampi of MTLE patients.

Focal thinning of the cerebral cortex in multiple sclerosis.

Brain atrophy as determined by quantitative MRI can be used to characterize disease progression in multiple sclerosis. Many studies have addressed white matter (WM) alterations leading to atrophy, while changes of the cerebral cortex have been studied to a lesser extent. In vivo, the cerebral cortex has been difficult to study due to its complex structure and regional variability. Measurement of cerebral cortex thickness at different disease stages may provide new insights into grey matter (GM) pathology. In the present investigation, we evaluated in vivo cortical thickness and its relationship to disability, disease duration, WM T2 hyper-intense and T1 hypo-intense lesion volumes. High-resolution MRI brain scans were obtained in 20 patients with clinically definite multiple sclerosis and 15 age-matched normal subjects. A novel method of automated surface reconstruction yielded measurements of the cortical thickness for each subject's entire brain and computed cross-subject statistics based on the cortical anatomy. Statistical thickness difference maps were generated by performing t-tests between patient and control groups and individual thickness measures were submitted to analyses of variance to investigate the relationship between cortical thickness and clinical variables. The mean overall thickness of the cortical ribbon was reduced in multiple sclerosis patients compared with controls [2.30 mm (SD 0.14) versus 2.48 mm (SD 0.11)], showing a significant main effect of group (controls versus patients). In patients, we found significant main effects for disability, disease duration, T2 and T1 lesion volumes. The visualization of statistical difference maps of the cortical GM thickness on inflated brains across the cortical surface revealed a distinct distribution of significant focal thinning of the cerebral cortex in addition to the diffuse cortical atrophy. Focal cortical thinning in frontal [2.37 mm (SD 0.17) versus 2.73 mm (SD 0.25)] and in temporal [2.65 mm (SD 0.15) versus 2.95 mm (SD 0.11)] brain regions was observed, even early in the course of the disease or in patients with mild disability. Patients with longstanding disease or severe disability, however, presented additionally with focal thinning of the motor cortex area [2.35 mm (SD 0.19) versus 2.74 mm (SD 0.15)]. We conclude that in vivo measurement of cortical thickness is feasible in patients suffering from multiple sclerosis. The data provide new insight into the cortical pathology in multiple sclerosis patients, revealing focal cortical thinning beside an overall reduction of the cortical thickness with disease progression.