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To understand neuronal mechanisms for manipulating and/or integrating information in working memory processes, we examined functional interactions among prefrontal neurons exhibiting various task-related activities by cross-correlation analysis. Among 168 neuron pairs isolated, 84 (50%) had significant peaks in cross-correlograms (CCGs); 30 had excitatory central peaks at time 0, 38 had excitatory peaks displaced from time 0, 13 had inhibitory central peaks, and three had both excitatory and inhibitory peaks displaced from time 0. Although significant interactions were observed among prefrontal neurons having various task-related activities, the information flow is present from prefrontal neurons having cue-period activity to neurons having oculomotor activity through neurons having delay-period activity. In addition, neuron pairs both having delay-period activity tended to have significant excitatory peaks in CCGs. Further, neuron pairs that had excitatory central peaks in CCGs tended to have similar directional preferences in task-related activities, and this similarity was the highest in neuron pairs both having cue-period activity. Neuron pairs that had displaced peaks in CCGs also showed similarity in directional preferences in task-related activities, and this similarity was also higher in neuron pairs both having cue-period activity. Interactions between neurons exhibiting task-related activity with different directional preferences increase as the temporal sequence of the task progresses. These results suggest that these interactions play an important role for manipulating and integrating information.

Neuronal Interactions Related to Working Memory Processes in the Primate Prefrontal Cortex Revealed by Cross-correlation Analysis