High resolution evoked potential imaging of the cortical dynamics of human working memory.

High resolution evoked potentials (EPs), sampled from 115 channels and spatially sharpened with the finite element deblurring method, were recorded from 8 subjects during working memory (WM) and control tasks. The tasks required matching each stimulus with a preceding stimulus on either verbal or spatial attributes. All stimuli elicited a central P200 potential that was larger in the spatial tasks than in the verbal tasks, and larger in the WM tasks than in the control tasks. Frequent, non-matching stimuli elicited a frontal, positive peak at 305 msec that was larger in the spatial WM task relative to the other tasks. Irrespective of whether subjects attended to verbal or spatial stimulus attributes, non-matching stimuli in the WM tasks also elicited an enhanced P450 potential over the left frontal cortex, followed by a sustained potential over the superior parietal cortex. A posterior P390 potential elicited by infrequent, matching stimuli was smaller in amplitude for both spatial and verbal WM tasks compared to control tasks, as was a central prestimulus CNV. These results indicate that WM is a function of a distributed system with both task-specific and task-independent components. Lesion studies and course temporal resolution functional imaging methods, such as PET and fMRI, tend to paint a fairly static picture of the cortical regions which participate in the performance of WM tasks. In contrast, the fine-grain time resolution provided by imaging brain function with EP methods provides a dynamic picture of subsecond changes in the spatial distribution of WM effects over the course of individual trials, as well as evidence for differences in the activity elicited by matching and non-matching stimuli within sequences of trials. This information about the temporal dynamics of WM provides a critical complement to the fine-grain spatial resolution provided by other imaging modalities.

Anticonvulsant prolongation of survival in adult murine lymphocytic choriomeningitis. II. Ultrastructural observations of pathogenetic events.

Because previous ultrastructural studies of murine lymphocytic choriomeningitis (LCM) had revealed only mononuclear cell infiltration with no cytopathology of target cells in the choroid plexus, ependyma, and leptomeninges, diazepam treatment was used to prolong survival for characterization of late pathogenetic events. Mice which were treated with diazepam and sacrificed 8, 9, and 10 days after intracerebral inoculation with LCM virus showed an increasing amount of inflammatory infiltration into choroid plexuses, leptomeninges, Virchow-Robin spaces, and ependyma. Mononuclear cells, lymphocytes, and polymorphonuclear (PMN) leukocytes increased in number as compared with terminally infected mice sacrificed 7 days after inoculation. Ultrastructurally, choroidal epithelial cells showed cytopathological changes varying from dilated endoplasmic reticulum through necrosis. Greater numbers of PMN leukocytes, macrophages, and activated macrophages and fewer undifferentiated mononuclear cells were seen in choroid plexuses of the drug-treated survivors. Virions and larger, more numerous arenavirus inclusions were present in choroid plexus and ependyma. Ultrastructurally the leptomeningitis was characterized by large numbers of activated macrophages. Choroidal epithelial necrosis appears to be the in vivo correlate of T-cell-mediated cytotoxicity in vitro.