Working Memory Task

To examine neuronal mechanisms of working memory processes, singleneuron activities recorded from DLPFC have been analyzed while monkeys performed a variety of working memory tasks. The working memory task often selected for neurophysiological experiments is the delayed-response task, because the delayed-response task requires working memory of spatial position (Goldman-Rakic, 1987; Funahashi and Kubota, 1994; Fuster, 1997) and because delayed-response deficits have been observed by the selective lesion of the cortex within and surrounding the principal sulcus (area 46) (Goldman-Rakic, 1987; Funahashi et al., 1993a; Petrides, 1994; Fuster, 1997). Fuster and Alexander (1971) and Kubota and Niki (1971) were the investigators who first examined single-neuron activity in DLPFC while monkeys performed a manual delayed-response or delayed alternation task. Since then, many studies have been performed to examine the characteristics of memory-related activity and other types of activity in the prefrontal cortex using the delayed-response task.

Funahashi et al. (1989) introduced an oculomotor version of the delayed-response (ODR) task (Fig. 1). In this task, the monkey was sat in a monkey chair and faced a TV monitor in a dark room. After about a 5 sec inter-trial interval, a central fixation target was presented at the center of the TV monitor. While the monkey maintained fixation at the fixation target, a visual cue was briefly (0.5 sec) presented randomly at one of the 4 or 8 predetermined peripheral positions. Then, the delay period (usually 3 sec) was introduced. During the visual cue presentation and the delay period, the monkey was required to maintain fixation at the fixation target. At the end of

And Genome Sequencing

Figure 1: Schematic drawings of an oculomotor version of the delayed-response task (ODR task) and three examples of task-related activity recorded from the prefrontal cortex while monkeys performed the ODR task. C, D, R indicate cue period, delay period, and response period, respectively. Delay length was 3 sec.

Figure 1: Schematic drawings of an oculomotor version of the delayed-response task (ODR task) and three examples of task-related activity recorded from the prefrontal cortex while monkeys performed the ODR task. C, D, R indicate cue period, delay period, and response period, respectively. Delay length was 3 sec.

the delay period, the fixation target was extinguished. This was the go signal for the monkey to make a saccade to the position where the visual cue had been presented. If the monkey made a correct saccade within a limited time (usually 0.4 to 0.5 sec), a liquid reward was given.

As is shown in Figure 1, we could observe three types of task-related activity (cue-period activity, delay-period activity, and response- period activity) while monkeys perfprmed the ODR task (Funahashi et al., 1989, 1990; Takeda and Funahashi, 2002).

2.2 Cue-Period Activity

A large number of neurons in DLPFC showed transient excitation or inhibition when the visual cues were presented during performances of working memory tasks. This transient activation responded to the visual cue presentation is called cue-period activity. Funahashi et al. (1990) found cue-period activity in 28% of task-related neurons while monkeys performed the ODR task. Most (93%) of cue-period activity showed transient excitation, but the remaining (7%) showed transient inhibition. The response latencies of excitatory cue-period activity were distributed from 37 to 309 ms with a median of 116 ms. In addition, most (96%) of cue-period activity were directional, such that cue-period activity was observed only when the visual cues were presented at certain areas in the visual field. Majority (71%) of cue-period activity had the best directions toward the visual field contralateral to the recording hemisphere.

The prefrontal cortex receives strong inputs from the posterior parietal cortex and the inferior temporal cortex (Goldman-Rakic, 1987; Fuster, 1997). Therefore, visual responses were also observed during the tasks in which visual stimuli had no behavioral significance to the monkey (e.g. a visual probe task). Funahashi et al. (1990) found no difference in the response magnitude and the tuning function of visual responses between the ODR task and the visual probe task. It has been shown that prefrontal visual neurons had visual receptive fields in the visual field (Mikami et al., 1982; Suzuki and Azuma, 1983). The centers of the visual receptive fields were located mainly in the visual field contralateral to the recorded hemisphere and the mean width of the receptive field was about 1/4 of the visual field. These characteristics agree with the characteristics of cue-period activity observed during delayed-response performances (Funahashi et al., 1990). Therefore, cue-period activity appears to be a visual response to the visual cue, and the characteristics of cue-period activity would correspond to the characteristics of visual receptive fields of prefrontal neurons.

2.3 Response-Period Activity

Response-period activity includes movement-related activity and post-trial activity. Since Kubota and Niki (1971) first reported movement- related activity in the prefrontal cortex, movement-related activity has been observed in tasks using manual responses (Niki and Watanabe, 1976; Kubota and Funahashi, 1982; Sawaguchi, 1987) as well as oculomotor responses (Joseph and Barone, 1987; Boch and Goldberg, 1989). Movement-related activity usually begins before the initiation of the behavioral response, and often persists during the behavioral execution. Moreover, this activity is often differential (Niki and Watanabe, 1976) or directional (Kubota and Funahashi, 1982), i.e. neuronal activation occurs when the movement directs one or a few particular directions. Therefore, it has been concluded that movement- related activity in the prefrontal cortex is related to the initiation or execution of the response behavior (Fuster, 1997).

However, the neurophysiological study using saccadic eye movements revealed that, although many prefrontal neurons showed saccade- related activity, the great majority of this activity was post-saccadic (Joseph and Barone, 1987; Funahashi et al., 1991). Post-saccadic activity observed in the prefrontal cortex had some features (Funahashi et al., 1991). First, post-saccadic activity was observed only during saccades for the task and not observed during spontaneous saccades outside the task. Second, a great majority of post-saccadic activity exhibited directional selectivity. The evidence that the distributions of preferred directions and tuning widths were similar between post-saccadic activity and pre-saccadic activity in the prefrontal cortex suggests that post-saccadic activity could be a feed-back signal from the oculomotor centers. Third, Goldman-Rakic et al. (1990) showed that the termination of excitatory delay-period activity coincided with the initiation of post-saccadic activity by population analyses of prefrontal activities. As is seen in Figure 1, excitatory delay-period activity usually terminated rapidly once response behavior was initiated. Therefore, post-saccadic activity has been considered to act as a reset signal to terminate delay-period activity, which becomes unnecessary information once the monkey performed a response behavior. Since hand and arm movement disorders and oculomotor disorders are not observed in prefrontal patients (Fuster, 1997; Stuss and Knight, 2002), the prefrontal cortex does not seem to directly participate in the initiation and the execution of motor behavior. Instead, since the prefrontal cortex has been considered to play an important role for executive control (Smith and Jonides, 1999; Funahashi, 2001), the prefrontal cortex might send regulatory signals to other cortical areas and receive feedback information from these cortical areas to perform multiple operations coordinately. Therefore, although some neurons having pre-saccadic activity actually participate in motor controls, we had better consider that a majority of neurons having movement-related response-period activity may participate in executive control processes.

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