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In order to investigate the effects of a partial cholinergic deafferentation on the functional activity of the cortex, the cerebral metabolic rate of glucose (CMRGlu) was measured with positron emission tomography and 18F-2-fluoro-2-deoxy-D-glucose in 5 baboons (Papio anubis) both before and serially following stereotaxic electrocoagulation of the left nucleus basalis of Meynert (NbM). Four days postlesion, significant metabolic depression was present in the entire ipsilateral cerebral cortex, most marked in the frontotemporal region, and which slowly recovered close to normal within 6-13 weeks. Postmortem studies showed that the lesions were located largely in the NbM, and that a significant decrease in choline-acetyltransferase (ChAT) activity was present in the ipsilateral frontal, temporal and parietal cortices. The animal with the most limited histological lesion showed the least decrease in both ChAT activity and CMRGlu. There was a highly significant linear correlation between the regional cortical decreases in CMRGlu (early postlesion data) and in ChAT activity. These results indicate that cholinergic deafferentation induces a proportional metabolic depression in the cortex. However, compensatory mechanisms operate to restore the cortical metabolic activity gradually despite sustained cholinergic denervation, pointing to pre- and/or postsynaptic adaptation (plasticity). Moreover, unilateral NbM lesions also induced a significant reduction in contralateral CMRGlu, which also demonstrated recovery. Several mechanisms are discussed to explain this contralateral effect, but the most likely implicates a transcallosal depression of function as a result of ipsilateral effects of the NbM lesion. These metabolic effects of cholinergic deafferentation in the primate provide new insight into the mechanisms of cortical dysfunction, and the recovery thereof, following subcortical lesions. In addition, our findings have some relevance to the cortical consequences of cholinergic deafferentation observed in dementia of Alzheimer type.

The effects of chronic (7 days) intracortical GABA infusions were investigated in both naturally photosensitive and non-photosensitive baboons. Bilateral and unilateral infusions into motor and occipital regions blocked photosensitivity, while premotor and prefrontal cortex infusions had no effect on the electro-clinical manifestations of this type of reflex epilepsy; the monkeys with prefrontal GABA infusions, however, showed selective attention deficits, detected with the delayed response test. In all cases a GABA withdrawal syndrome, appearing as epileptogenic spontaneous activity localized to the infused sites, was found at the cessation of GABA application. We conclude that GABAergic systems localized at discrete cortical areas play an important role in photosensitivity and in the modulation of cognitive processes in the monkey.

Kainic acid (KA) is known as a powerful convulsant and neurotoxic agent. When intracerebrally administered it causes repetitive seizures for about 1 or 2 days and brain damage both locally and in several remote brain regions. In the present paper the long-term effects of intrahippocampal KA administration are reported. Doses from 0.1 to 3.0 micrograms of KA were injected in the right hippocampus of Wistar rats and both the behaviour and EEG were observed during a period of about 3 months. Following KA doses of 0.8-2.0 micrograms, 4 distinct phases were observed: (1) acute phase which lasted 1-2 days and corresponded to the pattern of repetitive seizures as already described; (2) silent phase (5-21 days) which was characterized by a progressive return to apparently normal EEG and behaviour except for some aggressive behaviour in those animals receiving the highest doses; (3) phase of spontaneous recurrent seizures (these seizures started 6-22 days after KA injections and were mostly triggered upon handling and recurred approximately 2 times by day for about 30 days; usually they resembled the amygdaloid kindled seizures); and (4) post-seizure phase where no more seizures were observed but significant spiking activity in the amygdala recordings could be seen. Animals receiving KA doses of 0.1-0.4 microgram did not evolve beyond the acute phase whereas those receiving 3.0 micrograms died during this first phase. Neuropathological examination revealed dose-dependent alterations. These serial events offer a new method to induce spontaneous recurrent seizures with brain damage.

The effect of monocular intermittent light stimulation (ILS) of either hemivisual field (HVF) of the full visual field (FVF) was examined in Papio papio with or without forebrain bisection. ILS of the HVF or the FVF in non-bisected baboons produced bisymmetrical and bisynchronous spike and wave which was followed by a self-sustained seizure without EEG evidence of hemispheric independence. ILS of the FVF in bisected baboons also produced bilateral spike and wave and self-sustained seizures of a similar nature. With ILS of the HVF in bisected baboons, EEG seizures lateralized largely to the contralateral hemisphere and when the ILS of the HVF was switched to the other eye similarly lateralized spike and wave and a self-sustained seizure were produced in the other hemisphere. These findings suggest that (a) the forebrain commissure, most probably the corpus callosum (and possibly the hippocampal commissure), plays a major but not unique role in the bisynchronization and generalization of the ILS-induced spike and wave and the self-sustained seizures, and (b) each hemisphere possesses independent cerebral excitability to the ILS.

400 mg of cimetidine were administered intramuscularly 60 minutes before the beginning of general anesthesia. The double blind experiment was conducted on 84 patients divided in two groups: cimetidine and control. As far as the gastric fluid volumes are concerned there was no difference between the two groups during general anesthesia, but acid secretion decreased significantly in the cimetidine group, pH values lower than 2.5 were observed in 33.3 p. cent at induction time and 34 p. cent at recovery time in the control group against 14.6 p. cent and 0 p. cent in the cimetidine group.

The effects of macular and peripheral retina coagulation were examined in photosensitive baboons, Papio papio (PP), with or without forebrain bisection. The temporal part of the macula and surrounding retina of the left eye were coagulated with an Argon laser and later confirmed histologically. In forebrain nonbisected baboons, intermittent light stimulation of the operated eye produced bisymmetrical and bisynchronous spikes and waves and self-sustained seizures. In forebrain-bisected baboons intermittent light stimulation of the operated eye produced spikes and waves and self-sustained seizures localized to the contralateral hemisphere. Subsequent stimulation of the nonoperated eye in the same animal produced spikes and waves and seizures either bilaterally or only in the opposite hemisphere when stimulation took place during the postictal silent period in the first hemisphere. In both cases, the tonic phase of the seizure was always bilateral but asymmetrical as shown by electromyographic recordings. Based on these data, it has been hypothesized that the tonic phase is mediated, in part, through crossed interreticular pathways, by one or both cerebral hemispheres. However, data are also compatible with a possible origin of the tonic phase of the seizure being partly localized in the medial frontal cortex. Results demonstrated (1) the usefulness of laser coagulation of the temporal portion of the macula and retina for the study of the functional independence between two cerebral hemispheres, (2) the critical role of the corpus callosum (CC) in bisynchronization and generalization of the intermittent light stimulation (ILS)-induced seizure, (3) independent excitability of each cerebral hemisphere by the ILS, and (4) the critical role of cortical visual afferents for inducing epileptic phenomena in this species.

In Papio papio baboons chronically prepared for cortical and deep electroencephalographic recording, injection of kainic acid into the amygdala (7 animals) or temporal pole (2 animals) gave rise to focal epileptic discharges lasting 15 to 150 hours. Electrographically, the seizure activity spread ipsilaterally and contralaterally within the limbic system but did not become generalized. The principal associated motor signs were arrest of movement and oral automatisms. Histological examination after two to ten days demonstrated lesions (neuron loss and gliosis) at the injection site that varied according to the amount of kainic acid injected (2 to 68 microgram). "Remote" lesions occurred in the ipsilateral hippocampus (end-folium and Sommer sector) and neocortex (occipital and frontal regions). The hippocampal lesions were comparable to those previously described as consequent to status epilepticus.