The highest level of cerebral glucose metabolism occurs in PCC and RSC. The highest level of basal glucose metabolism in the monkey brain is in RSC and the anterior thalamus and these levels are elevated during performance of a delayed-response task (Matsunami et al., 1981). We have discussed the close laminar association of both high levels of glucose metabolism determined with the 2-deoxy-D-glucose method and anterior thalamic projections assessed with tritiated-amino acid injections (Vogt et al., 1997
). repeat these latter findings and provide the context of high cytochrome oxidase activity (). Thalamic termination is greatest to the granular layer of area 29 (undifferentiated layer III/IV) and layers III-IV of area 30. Projections to area 23 arise mainly from the medial pulvinar and lateroposterior nuclei and these were not included in the amino acid injection shown in ; hence thalamocortical connections to area 23 are not demonstrated in this case.
Figure 2 Morphological context of metabolic activity in PCC in monkeys. A. 2-deoxy-D-glucose utilization coded for four levels of utilization and thalamic projections to RSC shown with a tritiated-amino acid injection (hatched) into the anterior thalamic nuclei (more ...)
High basal glucose metabolism overlaps with these latter layers on the ventral bank of the cingulate gyrus. Cytochrone c oxidase is a mitochondrial enzyme involved in oxidative phosphorylation and the density of activity generated by this enzyme is related to the density of mitochondria in a layer (Carroll and Wong-Riley, 1984
). Axon terminals arising from neurons in the anterior thalamic nuclei in rat have a large diameter, are very dense with mitochondria, and they form asymmetric, excitatory synapses in RSC (Vogt et al., 1981
). Moreover, thalamic lesions greatly reduce this enzyme’s activity in thalamoreceptive layers I–IV of RSC (Van Groen et al., 1993
) suggesting that thalamic driving is critical to metabolic processes in RSC.
The rodent findings are extended for monkey in . The highest level of cytochrome c oxidase activity is in RSC and adjacent area 23. A section of area 24 is provided at the asterisk in B for comparative purposes and it shows that ACC has only about 40% of the cytochrome c oxidase activity of areas 23 and 30. Area 7m (not shown) has a level of activity similar to that of area 23b. This figure also shows the effects of a midcingulotomy lesion in the contralateral hemisphere on cytochrome c oxidase activity (). Notice in this section the elevated gliosis in the white matter, general shrinkage of the ventral cingulate gyrus and massive reduction in cytochrome c oxidase activity. Reduced cytochrome activity is most prominent in the thalamorecipient layers III/IV of areas 29, 30, and 23 as emphasized with the arrows in the figure. Thus, midcingulotomy lesions de-afferent PCC and RSC and this includes sectioning of thalamic afferents that travel through the cingulum bundle to terminate in the PCC.
The PCC/PrCC has the highest level of metabolism in human brain (Andreasen et al., 1995
; Maquet et al., 1997
; Minoshima et al., 1997
). We evaluated rCMRGlu in 32 resting control subjects in regions of interest selected from the medial surface and three levels of the thalamus as shown in . Although the highest level of activity was in the PrCC, it was also quite high in PCC and the three samples from thalamus. The ACC and MCC were much lower and that in RSC was strikingly low. In view of the observations above for monkey, the latter observation for human RSC either reflects a substantial species difference or the limits of PET resolution in defining RSC have been reached. The latter is suspected both because this is a small region and it winds around the splenium and includes a variable amount of white matter that is likely proportionately greater than for the other regions and reduces the apparent level of glucose metabolism (i.e., partial volume effect bias). The slide-autoradiographic measure of glucose uptake in the monkey has a much greater precision and demonstrates laminar localizations that are not possible with human PET imaging. The most important conclusion from this histochemical analysis is that RSC likely has a similar or even higher level of glucose metabolism to PCC/PrCC and the RSC provides a critical link between the brainstem arousal system and cortical mechanisms of conscious awareness as discussed in the next section.
Analysis of rCMRGlu in the vegetative state shows reduced activity in a large region of prefrontal cortex and a posterior, medial reduction in PCC/PrCC that might include RSC. In spite of the large prefrontal reductions, the crucial connection with this region that was disrupted in vegetative state was in PCC. As the relevant area overlaps the callosal sulcus, it is quite possible that the critically impaired connection is actually with RSC. Additionally, the thalamus also has reduced rCMRGlu in vegetative state (S. Laureys, unpublished observations) and this emphasizes further the critical linkage between the thalamus and PCC/PrCC from brainstem arousal systems.