V. K. Kruchinin

Neurophysiological correlates of delayed visual differentiation tasks in monkeys: the effects of the site of intracortical blockade of NMDA receptors.

A delayed visual differentiation task using stimuli of different colors was used in rhesus macaques to study the characteristics of visual recognition, short-term memory, and the responses of neurons recorded simultaneously in the visual and prefrontal areas of the cortex, along with their relationships with the site of intracortical (fields 17 or 46) perfusion of the glutamate receptor antagonist 2-amino-5-phosphonovaleric acid (APV). The behavioral characteristics and spike activity of individual cells in cortical fields 17 and 46 were recorded before and after perfusion with APV and after washing away of traces of APV. Multifactor dispersion analysis showed that the effect of APV in monkeys consisted of decreases in the probability of correct responses, leading to a decrease (two-fold) in the duration of short-term storage of information and a significant increase in the motor reaction time. The probability of correct solutions depended on the site of APV perfusion in the cortex, while the motor response time was independent of the perfusion site. Perfusion of field 46 with APV, unlike perfusion of field 17, altered the spike activity only of neurons in the prefrontal cortex, while no significant changes were seen in the neuron activity of the visual cortex. The actions of APV were accompanied by significant desynchronization of neuron activity in these two areas as compared with the level of synchronization in normal conditions; after traces of APV were washed away, the extent of desynchronization decreased. The neurophysiological correlates of cognitive dysfunctions associated with degradation of visual recognition and short-term memory due to modification of glutamatergic structures by blockade of NMDA receptors are discussed.

Effect of NMDA on the activity of cortical glutaminergic structures in delayed visual differentiation in monkeys.

The effect of intracortical perfusion with the glutamate agonist NMDA on visual recognition and short-term memory, as well as on the responses of visual cortex neurons, were studied in rhesus macaques. A microdialysis technique was used in combination with multichannel microelectrode recording of single cortical cells in the immediate vicinity of the dialysis tube in a behavioral experiment in which the monkey had to solve a task involving delayed visual differentiation of stimuli of different colors. NMDA altered the characteristics of recognition in monkeys. The duration of information storage in short-term memory was increased significantly (2–4-fold), and there was a significant reduction in the motor response time for all delay periods. These changes were accompanied by a significant rearrangement of neuron activity in the visual cortex at all stages of the behavioral task. At different stages of the task, 70–85% of the neurons showed 2–5-fold increases in activity, while 6–20% showed reductions in activity. These results demonstrate an involvement of visual cortex glutaminergic structures in the processes of visual recognition and short-term memory, as well as a nootropic effect obtained by intracortical administration of NMDA.

Neurophysiological correlates of improvements in cognitive characteristics in monkeys during modification of NMDA-ergic structures of the prefrontal cortex

The effects of modification of NMDA-ergic structures by microdialysis perfusion in the prefrontal cortex (field 8) with NMDA glutamate (2 mM) on visual recognition and short-term memory (STM) were studied in rhesus macaques, using methods based on the deferred differentiation of stimuli of different colors. Impulse activity of neurons in the prefrontal and visual cortex was measured during these experiments, both before and after administration of NMDA. NMDA increased (2-fold) the duration of short-term retention of information and significantly reduced the latent period of the motor response at all delay periods, and also produced significant changes in neuron activity in the prefrontal cortex: depending on the stage of behavior, activity decreased in 60–75% of neurons and increased in 8–26%. NMDA produced significant increases in the cross-correlation coefficients between the responses of neurons in the visual and prefrontal cortex. The results showed that glutaminergic structures in the prefrontal cortex are involved in processes of visual recognition and STM in monkeys. The effect of NMDA, which synchronized cortical neuronal processes, improved the short-term understanding of visual information.

Neurophysiologic correlates of the decision-making processes in the cerebral cortex of monkeys during visual recognition

The impulse activity of groups of neurons of the visual, prefrontal, and inferotemporal cortex was recorded simultaneously in behavioral experiments on monkeys solving a problem of delayed visual differentiation of variously colored stimuli. The neurophysiological correlates of the decision-making processes were studied. Erroneous motoric reactions were accompanied in all monkeys by significant reorganizations of the patterns of impulse activity of the neurons. In the case of correct solutions of the monkeys, synchronization in time and cross-correlation which was significant in magnitude between the activity of the groups of neurons were observed. Incorrect solutions were accompanied by desynchronization and by a decrease in cross-correlation between the activity of these groups of neurons. Possible decision-making mechanisms and the causes of the desynchronization of the informational processes during erroneous reactions are discussed.

An antioxidant-induced improvement in the cognitive characteristics of monkeys: Neurophysiological correlates in the visual cortex

After the injection of the antioxidant, oxymethacil (4–5 μg/kg), in an investigation in monkeys of the processes of delayed visual recognition, their cognitive characteristics were significantly improved.: the duration of the short-term storage of information increased (by a factor of 2–3) and the time of the motor reaction decreased. The improvement of the cognitive characteristics was accompanied by changes in the neuronal activity in the visual cortex at all stages of recognition. The activity of the majority of the neurons increased in the case of discrimination without delay; it decreased significantly in the case of delayed discrimination. The administration of oxymethacil induced an increase in the auto-and cross-correlation coefficients in the respondent reactions of the recorded groups of neurons. The results obtained suggest that oxymethacil possesses nootropic properties, and the participation of the visual cortex of monkeys in the realization of these properties for the improvement of cognitive characteristics.

Influence of an antioxidant on the impulse activity of neurons of the prefrontal and inferotemporal cortex during visual recognition in monkeys

The impulse activity of individual neurons of the prefrontal and inferotemporal cortex was recorded during the performance of a task of delayed visual differentiation of stimuli of various colors in monkeys before and after the systemic administration of the antioxidant, oxymethacil (4–5 mg/kg). The improvement in cognitive characteristics induced by oxymethacil was accompanied by changes in the activity of neurons of the prefrontal cortex in which activation dependant upon the stage of recognition and intensifying during an increase in the duration of the delay predominated. Inhibition of activity predominated during recognition without delay in these neurons; by contrast, activation predominated in neurons of the inferotemporal cortex under these conditions. During delayed differentiation, the activity of these neurons under the influence of oxymethacil changed principally in the same way as in neurons of the prefrontal cortex: activation predominated in the majority of the stages of recognition. Oxymethacil induced a substantial increase in the coefficients of cross correlation between simultaneous respondent reactions of groups of neurons in these different areas of the cortex. The results obtained attest to the contribution of neuronal structures of the prefrontal and inferotemporal cortex to the improvement of cognitive characteristics of monkeys in the presence of the effect of oxymethacil, and to the increase in synchronization of informational processes in these regions of the cortex.

Participation of cholinergic structures of the prefrontal and inferotemporal cortex in the processes of visual recognition in monkeys.

Monkeys performed a task of delayed visual differentiation of differently colored stimuli in behavioral experiments. The impulse activity of individual neurons of the prefrontal and inferotemporal cortex before and after the systemic administration of a blocker of M-cholinoreceptors, amyzil (0.8–1.0 mg/kg), was recorded simultaneously. Deterioration of the characteristics of recognition induced by amyzil was accompanied mainly by a significant increase in the activity of neurons of the prefrontal cortex which was dependant on the stage of recognition, and intensified with an increase in the delay interval. The impulse activity of the neurons of the inferotemporal cortex varied in the process without a regular pattern: at some stages of recognition it increased, at others it was inhibited. Amyzil induced a substantial decrease in the coefficients of cross correlation between the simultaneous respondent reactions of groups of neurons of the prefrontal and inferotemporal cortex. The results obtained point to the fact that the cholinergic structures of the inferotemporal and prefrontal cortex participate, at various stages of visual recognition in monkeys, in the formation of the dynamic functional systems which make their specific contribution to informational processes.

Dynamics of the impulse activity of neurons of the neocortex of monkeys in a visual recognition task after brief oxygen deprivation

A model of brief oxygen supply disruption was created in monkeys trained to a delayed visual spatial choice. A substantial reorganization of the impulse activity of neurons of the visual and prefrontal cerebral cortex, accompanied by disturbances in behavioral reactions, was observed during brief hypoxia (2.5 min); the motor reaction was not restored for several hours in the monkeys during a delayed visual spatial choice. The reorganization of the activity consisted in the appearance of successive phases of hyperactivation and inhibition. The frequency of the impulse activity in the phase of hyperactivation was higher in prefrontal cortex neurons. Successive phases of inhibition and hyperactivation were also identified in the posthypoxic period of restoration in the structure of the activity. The duration of the posthypoxic inhibition and the ratio of the frequencies of posthypoxic hyperactivation to the baseline frequency in the reactions of prefrontal cortex neurons was substantially greater than in the neurons of the visual cortex.

Processes of visual recognition in monkeys and their neuronal correlates in the visual cortex: the influence of a blocker of M-cholinoreceptors.

The activity of individual neurons of the visual cortex was recorded simultaneously in behavioral experiments on monkeys before and after the systemic administration of a blocker of M-cholinoreceptors, amizil (0.8–1.0 mg/kg). The animals were trained to delayed visual differentiation of stimuli of various colors. After the administration of amizil, the characteristics of recognition deteriorated substantially: the duration of the storage of information in short-term memory sharply declined, while the time of the motoric reaction increased. The deterioration of these characteristics was accompanied by inhibition of the activity of the neurons of the visual cortex, inhibition which depended on the stage of recognition, and which intensified when there was an increase in the delay interval. The results obtained suggest that cholinergic mechanisms of the visual cortex are included in visual recognition, and apparently play various functional roles at various stages of behavior.

Correction of a disturbance in visual recognition in monkeys with the aid of an antioxidant

The influence of an effective antioxidant, oxymethacil, was studied in a model of the disruption of visual recognition induced by the antidepressant fluoracyzine. The normal discrimination of black and white visual stimuli in monkeys is restored with the systemic administration of oxymethacil in a dose of 3 mg/ kg following disruption brought about by the effect of fluoracyzine. The discrimination of colored visual stimuli, as in the norm, is restored following the systemic administration of oxymethacil in a dose of 4 mg/kg. The results obtained attest to the corrective properties of oxymethacil.