The rhinal cortex (areas 28, 35 and 36) has received increased attention because of neuropathological reports linking pathology to this region to such debilitating illnesses as Alzheimer's disease and schizophrenia. We have been investigating the role of the entorhinal (area 28) and perirhinal (areas 35 and 36) cortices in information processing to understand how pathology in this region might result in cognitive and anatomical defects associated with schizophrenia. One of the proposed primary deficits associated with the medial temporal pathology is a problem with temporal lobe - prefrontal cortical functional interaction. We previously demonstrated that in the absence of each cortical region the monkey is capable, though mildly impaired, of learning the recognition memory task delayed non-matching to sample, however, with combined removal the monkey becomes incapable of relearning the task. While this confirms functional interaction between the two cortical regions it does not demonstrate information transfer from one region to the other. We have also begun to study the effects of maldevelopment of this interaction by examining anatomical and functional changes as a result of neonatal removal of the temporal lobe limbic areas including the entorhinal cortex. We examined the performance of monkeys with neonatal limbic lesions on tasks known to be sensitive to, frontal damage, or temporal lobe damage or to either frontal or temporal lobe damage. Our data suggest that on tasks sensitive to temporal lobe damage the pattern and severity of cognitive impairment after neonatal limbic lesions is somewhat less than that after similar lesions as an adult. However, in contrast, we have preliminary evidence that indicates that on tasks known to be sensitive to frontal damage (e.g. recency) that monkeys with neonatal lesions may show a greater impairment compared with animals with adult lesions. Thus, in addition to the social and emotional deficits reported after neonatal lesions but not after adult lesions, there may also be a cognitive impairment related to frontal dysfunction. We have also examined, using proton magnetic spectroscopy (1H-MRS), whether the neonatal limbic lesions result in abnormal prefrontal levels of N-acetyl-aspartate, an amino acid compound found exclusively in neurons. Monkeys with the neonatal limbic lesions were found to have a significantly reduced NAA ratios in the prefrontal cortex as compared with normal controls and monkeys with limbic lesions during adulthood. Similar decreases in the prefrontal cortex had been reported for schizophrenic patients. This result again demonstrates functional maldevelopment of the prefrontal cortex after neonatal temporal lobe limbic lesions. These data taken together with our neurobehavioral findings and the neurochemistry results (see Z01 MH 02575-05 CBDB) is consistent with the proposal that early limbic damage may be critical for the pathophysiology of schizophrenia. The increased functional role of the rhinal cortex has directed our study of its anatomical connections outside of the hippocampus to further understand important information processing pathways. We have shown that the entorhinal (area 28) and some of the perirhinal cortex (areas 35 and 26) have extensive projections to the medial thalamic region (e.g. anterior nuclei, medial dorsal nucleus), as well as other structures in the striatum such as the nucleus accumbens and caudate nucleus. These subcortical projections of the rhinal cortex are much more extensive than previously demonstrated and provide an extensive anatomical system by which the rhinal cortex and the prefrontal cortex may interact. We have begun to study the cortico- cortical connections of the rhinal cortex in order to define the afferent input to the perirhinal cortex since many of the cortical connections including those to the prefrontal cortex arise from this region. Perirhinal cortex (areas 35 and 36) receives converging sensory input as well as projections from the entorhinal, parahippocampal, and hippocampal cortices. This region, critically important for cognitive processes often associated with the hippocampus, may not be as extensive as recently reported.
