Previously, we demonstrated that enhancing cholinergic activity during a working memory (WM) task improves performance and reduces blood flow in the right anterior middle/superior frontal cortex, an area known to be important for WM. The purpose of this study was to evaluate the interaction between WM task demands and cholinergic enhancement on neural responses in the prefrontal cortex. Regional cerebral blood flow (rCBF) was measured using H 2 15 O and positron emission tomography, as 10 young healthy volunteers performed a parametrically varied match-to-sample WM for faces task. For each item, a picture of a face was presented, followed by a delay (1, 6, 11, or 16 sec), then by the presentation of two faces. Subjects were instructed to identify which face they previously had seen. For control items, nonsense pictures were presented in the same spatial and temporal manner. All conditions were performed during an intravenous infusion of saline and physostigmine (1 mg/hr). Subjects were blind to the substance being infused. Reaction time increased significantly with WM delay, and physostigmine decreased reaction time across delay conditions. Significant task-related rCBF increases during saline infusion were seen in superior frontal, middle frontal, and inferior frontal regions, and the response magnitudes in the regions increased systematically with task difficulty. In all of these prefrontal regions, physostigmine administration significantly reduced rCBF during task, particularly at longer task delays, so that no correlation between task delay and rCBF was observed. In the ventral visual cortex, physostigmine increased rCBF at longer task delays in medial regions, and decreased rCBF over delay conditions in lateral cortical areas. These results indicate that, during cholinergic potentiation, brain activity in prefrontal regions is not modulated by increases in WM task demands, and lends further support to the hypothesis that cholinergic modulation enhances visual processing, making the task easier to perform, and thus, compensate for the need to recruit prefrontal cortical regions as task demands increase.

Primate extrastriate visual cortex is organized into an occipitotemporal pathway for object vision and an occipitoparietal pathway for spatial vision. Correlations between normalized regional cerebral blood flow values (regional divided by global flows), obtained using H 2 15 O and positron emission tomography, were used to examine functional associations among posterior brain regions for these two pathways in 17 young men during performance of a face matching task and a dot-location matching task. During face matching, there was a significant correlation in the right hemisphere between an extrastriate occipital region that was equally activated during both the face matching and dot-location matching tasks and a region in inferior occipitotemporal cortex that was activated more during the face matching task. The corresponding correlation in the left hemisphere was not significantly different from zero. Significant intrahemispheric correlations among posterior regions were observed more often for the right than for the left hemisphere. During dot-location matching, many significant correlations were found among posterior regions in both hemispheres, but significant correlations between specific regions in occipital and parietal cortex shown to be reliably activated during this spatial vision test were found only in the right cerebral hemisphere. These results suggest that (1) correlational analysis of normalized rCBF can detect functional interactions between components of proposed brain circuits, and (2) face and dot-location matching depend primarily on functional interactions between posterior cortical areas in the right cerebral hemisphere. At the same time, left hemisphere cerebral processing may contribute more to dot-location matching than to face matching.

We previously reported selective activation of regional cerebral blood flow (rCBF) in occipitotemporal cortex during a face matching task (object vision) and activation in superior parietal cortex during a dot-location matching task (spatial vision) in young subjects, The purpose of the present study was to determine the effects of aging on these extrastriate visual processing systems. Eleven young (mean age 27 ± 4 years) and nine old (mean age 72 ± 7 years) male subjects were studied. Positron emission tomographic scans were performed using a Scanditronix PC1024–7B tomograph and H 2 15 O to measure rCBF. To locate brain areas that were activated by the visual tasks, pixel-by-pixel difference images were computed between images from a control task and images from the face and dot-location matching tasks. Both young and old subjects showed rCBF activation during face matching primarily in occipitotemporal cortex, and activation of superior parietal cortex during dot-location matching. Statistical comparisons of these activations showed that the old subjects had more activation of occipitotemporal cortex during the spatial task and more activation of superior parietal cortex during the object task than did the young subjects. These results show less functional separation of the dorsal and ventral visual pathways in older subjects, and may reflect an age-related reduction in the processing efficiency of these visual cortical areas.