Directional Delay-period Activity Research Articles

Change of information represented by thalamic mediodorsal neurons during the delay period.

The thalamic mediodorsal (MD) nucleus plays an important role in transforming visual information into motor information during spatial working-memory performances. To understand the neural mechanism of this transformation process, we examined whether or not the information represented in individual MD neuron's activity changes during a trial of the task. Two monkeys performed two oculomotor delayed-response tasks (an ordinary and a rotatory oculomotor delayed-response task). As MD neurons show directional delay-period activity, we compared the directional selectivity of the same MD neuron between these two tasks and determined whether the activity represented the cue direction or the saccade direction. Among the 26 MD neurons that showed directional delay-period activity, representing information of 27% of neurons gradually altered from the visual domain to the oculomotor domain, while the remaining neurons kept holding either the visual or the oculomotor information throughout the delay period. These results indicate that gradual alteration of information representing in individual MD neurons during the delay period plays an important role in spatial working-memory performance. This alteration could be performed by interactions among MD neurons representing different information during the delay period.

Prefrontal Delay-Period Activity Reflects the Decision Process of a Saccade Direction during a Free-Choice ODR Task

To examine how delay-period activity participates in the decision of a saccade direction, we analyzed prefrontal activity while monkeys performed 2 tasks: oculomotor delayed-response (ODR) and self-selection ODR (S-ODR) tasks. In the ODR task, monkeys were required to make a memory-guided saccade to the cue location after a 3-s delay. In the S-ODR task, 4 identical visual cues were presented simultaneously during the cue period and monkeys were required to make a saccade in any one direction after the delay. Delay-period activity was observed in both tasks in the same neuron with similar directional preferences. Neurons with delay-period activity were classified into several groups based on the temporal pattern of the activity itself and of the strength of the directional selectivity. Among these, neurons with an increasing type of delay-period activity with persistent directional selectivity throughout the delay period in the ODR task also showed directional delay-period activity in the S-ODR task. These results indicate that an increasing type of delay-period activity, which is thought to represent motor information, plays an important role in generating and enhancing directional bias in the S-ODR task and therefore contributes significantly to the decision process of the saccade direction in the S-ODR task.

Contributions of prefrontal cue-, delay-, and response-period activity to the decision process of saccade direction in a free-choice ODR task

To examine how the dorsolateral prefrontal cortex (DLPFC) contributes to the decision process of the saccade direction, we recorded single-neuron activity while two monkeys performed two oculomotor delayed-response (ODR) tasks. In an ordinary ODR task, monkeys were required to make a memory-guided saccade to the cue location after a 3-s delay. In a self-selection version of the ODR task (S-ODR), four identical visual cues were presented simultaneously at the cue period, and monkeys were required to make a saccade toward any one of four directions after a 3-s delay. By comparing the same neuron's activity between two tasks, we found (1) neurons having directional cue-period activity in the ODR task did not show directionally selective activity in the S-ODR task, (2) neurons having directional pre-saccadic activity showed highly similar directional preferences in two tasks and exhibited temporal coupling between the onset of pre-saccadic activity and the initiation of saccadic eye movements, (3) neurons with directional delay-period activity in the ODR task exhibited similar directional preferences and showed gradual increase in the strength of the directional selectivity toward the end of the delay period in the S-ODR task. These results suggest that directional delay-period activity contributes to the decision process of the saccade direction in the S-ODR task, while directional cue-period and pre-saccadic activities do not. The gradual increase of the directional selectivity in delay-period activity might correspond to neural correlates of the decision process of the saccade direction in the S-ODR task.

Properties of delay-period neuronal activity in the primate prefrontal cortex during memory- and sensory-guided saccade tasks.

The dorsolateral prefrontal cortex (DLPFC) is involved in visuospatial short-term (or working) memory. Its cellular basis has been widely examined using the delayed-response paradigm in nonhuman primates. Sustained delay-period activity in DLPFC neurons with directional difference (i.e. directional delay-period activity) has been thought to represent visuospatial short-term (or working) memory. However, little is known about the activity of these neurons during a delay period when the sensory input remains. To address this issue, we examined neuronal activity in the DLPFC while macaque monkeys performed a memory-guided saccade (MGS) task and a delayed visually guided saccade (VGS) task. The MGS task required a memory-guided saccade for a remembered target location. The VGS task had the same temporal sequence as the MGS task, but the sensory stimulus remained during the delay period. We found that most of the DLPFC neurons with directional delay-period activity showed sustained activation during the 'delay' period in the VGS task only ('V-neurons', 49%), or in both tasks ('MV-neurons', 46%). Neurons showing directional delay-period activity in the MGS task only ('M-neurons') were only 5% of the DLPFC neurons with directional delay-period activity. These findings indicate that most DLPFC neurons that are active during the delay period are also active when the sensory stimulus remains, suggesting that DLPFC neurons driven by mnemonic information are also driven by sensory input. Such sustained representation of information should have potential utility in flexible cognitive controls of behaviour.

Neuronal activity representing visuospatial mnemonic processes associated with target selection in the monkey dorsolateral prefrontal cortex.

To investigate how visuospatial mnemonic and target selection processes are represented in the dorsolateral prefrontal cortex (PFC), we studied neuronal attributes of the dorsolateral PFC while monkeys were performing oculomotor delayed visual search (ODVS) and oculomotor delayed-response (ODR) tasks. In the ODVS task, the subject made a memory-guided saccade to a remembered target location that had been presented along with distractors before a delay period; in the ODR task, the target was presented without any distractors. A total of 252 neurons in the dorsolateral PFC showed directional delay-period activity and were divided into two groups; neurons that showed directional delay-period activity predominantly in the ODVS task (n=112), and those that showed such activity similarly in both the ODVS and ODR tasks (n=140). These neuronal groups shared similar temporal properties (i.e. onset latency, peak time of delay-period activity) and spatial tuning. Our findings suggest that the dorsolateral PFC contains a particular visuospatial memory system for information selected by target selection (selective attention), and this attention-memory system (or 'memory system for special use') appears to be represented in the dorsolateral PFC, in parallel with a more 'general' memory system that is not specifically associated with target selection.

Prefrontal Task-Related Activity Representing Visual Cue Location or Saccade Direction in Spatial Working Memory Tasks

To examine what kind of information task-related activity encodes during spatial working memory processes, we analyzed single-neuron activity in the prefrontal cortex while two monkeys performed two different oculomotor delayed-response (ODR) tasks. In the standard ODR task, monkeys were required to make a saccade to the cue location after a 3-s delay, whereas in the rotatory ODR (R-ODR) task, they were required to make a saccade 90 degrees clockwise from the cue location after the 3-s delay. By comparing the same task-related activities in these two tasks, we could determine whether such activities encoded the location of the visual cue or the direction of the saccade. One hundred twenty one neurons exhibited task-related activity in relation to at least one task event in both tasks. Among them, 41 neurons exhibited directional cue-period activity, most of which encoded the location of the visual cue. Among 56 neurons with directional delay-period activity, 86% encoded the location of the visual cue, whereas 13% encoded the direction of the saccade. Among 57 neurons with directional response-period activity, 58% encoded the direction of the saccade, whereas 35% encoded the location of the visual cue. Most neurons whose response-period activity encoded the location of the visual cue also exhibited directional delay-period activity that encoded the location of the visual cue as well. The best directions of these two activities were identical, and most of these response-period activities were postsaccadic. Therefore this postsaccadic activity can be considered a signal to terminate unnecessary delay-period activity. Population histograms encoding the location of the visual cue showed tonic sustained activation during the delay period. However, population histograms encoding the direction of the saccade showed a gradual increase in activation during the delay period. These results indicate that the transformation from visual input to motor output occurs in the dorsolateral prefrontal cortex. The analysis using population histograms suggests that this transformation occurs gradually during the delay period.

The effects of dopamine and its antagonists on directional delay-period activity of prefrontal neurons in monkeys during an oculomotor delayed-response task.

To examine the role of dopamine receptors in the memory field of neurons for visuospatial working memory in the prefrontal cortex (PFC), dopamine and its antagonists (SCH23390 for the D1-antagonist and sulpiride for the D2-antagonist) were applied iontophoretically to neurons of the dorsolateral PFC in monkeys that performed an oculomotor delayed-response task. In this task, the subject made a memory-guided saccade to a remembered target location that had been cued by a visuospatial stimulus (right, up, left, or down; 15 degrees in eccentricity) prior to a 4-s delay period. We focused here on PFC neurons that showed directional delay-period activity; i.e., an increased activity during the delay period, the magnitude of which varied significantly with the target location. Iontophoretic application of SCH23390 (usually 50 nA) decreased or increased the activities of most of these neurons (n=48/62, 77%); most neurons showed a decrease (n=43/62, 69%). For the neurons affected by SCH23390, a directional index of directional delay-period activity was attenuated by SCH23390, whereas the preferred direction was not greatly affected. The decreasing effect of SCH23390 was dose-dependent; the extent of the decrease was less with a lower dose (20-nA current) than with the ordinary dose (50-nA current), although the effect of the lower dose of SCH23390 on delay-period activity was similar in nature to that of the ordinary dose of SCH23390. Furthermore, the application of dopamine itself augmented directional delay-period activity in most of the neurons tested (n=12/16, 75%). Sulpiride did not have any significant effects in most of the neurons tested (n=15/17). These results suggest that the activation of D1-dopamine receptors play a facilitating role in the memory field of PFC neurons for visuospatial working memory processes.

Parallel visuospatial and audiospatial working memory processes in the monkey dorsolateral prefrontal cortex.

The dorsolateral area of the prefrontal cortex (PFC) in primates is involved in visuospatial working memory, but the cellular basis of spatial working memory for auditory information is poorly understood. Here we examined dorsolateral PFC neurons using visual and auditory oculomotor delayed-response tasks. We found that the dorsolateral PFC contains two groups of neurons, each showing directional delay-period activity depending on the location of the visual or auditory cue, suggesting that parallel neuronal processes for visual and auditory spatial working memory occur in the dorsolateral PFC.

Attenuation of delay-period activity of monkey prefrontal neurons by an alpha2-adrenergic antagonist during an oculomotor delayed-response task.

To examine the role of norepinephrine receptors in spatial working memory processes mediated by the prefrontal cortex (PFC), noradrenergic antagonists (yohimbine for alpha2, prazosin for alpha1, and propranolol for beta receptors) were applied iontophoretically to neurons of the dorsolateral PFC in rhesus monkeys that performed an oculomotor delayed-response (ODR) task. The ODR task was initiated when the monkeys fixated on a central spot on a computer monitor and consisted of fixation (1 s), cue (1 of 4 peripheral cues, 0.5 s), delay (fixation cue only, 4 s), and go periods. In the go period, the subject made a memory-guided saccade to the target location that was cued before the delay period. I focused on 49 neurons that showed directional delay-period activity, i.e., a sustained increase in activity during the delay period, the magnitude of which varied significantly with the memorized target location. Iontophoretic (usually 50 nA) application of yohimbine, but not prazosin or propranolol, significantly decreased the activities of most of the neurons with directional delay-period activity (n = 41/49, 81%). Furthermore, yohimbine attenuated the sharpness of tuning, examined by a tuning index, of delay-period activity and had a greater attenuating effect on delay-period activity than on background activity. These findings suggest that the activation of alpha2-adrenergic receptors in the dorsolateral PFC plays a modulatory role in neuronal processes for visuospatial working memory.

Noradrenergic Effects on Activity of Prefrontal Cortical Neurons in Behaving Monkeys

This chapter summarizes that iontophoretic application of the α 2 -receptor antagonist yohimbine to prefrontal neurons in the monkey attenuated delay-period activity, indicating that activation of α 2 receptors plays a critical role in maintaining the directional or mnemonic coding of prefrontal neurons. Of 57 neurons recorded during oculomotor delayed-response (ODR) performance, the researchers concentrate on 31 neurons that showed delay-period activity of which magnitude differed significantly with the direction of cue-response, because such directional delay-period activity has been suggested to play a central role in the working memory process for visuospatial information. These neurons are located in the principal sulcus or immediately adjacent cortex. It has been demonstrated that iontophoretic application of the selective α 2 -adrenergic receptor antagonist, yohimbine, attenuate the directional delay-period activity of prefrontal neurons during ODR performance. At the same time, yohimbine attenuated the sharpness of directional tuning, examined by fitting to a cosine function, of directional delay-period activity. These findings suggest that the activation of α 2 receptors plays a modulatory role in maintaining the directional tuning of delay-period activity of prefrontal cortical neurons during ODR performance. As the directional delay-period activity with tuning is considered to represent mnemonic coding for visuospatial working memory, it can be concluded that the activation of α 2 receptor plays a modulatory role in maintaining mnemonic coding of neuronal activity for the working-memory process in primate prefrontal cortex.

Mnemonic coding of visual space in the monkey's dorsolateral prefrontal cortex.

1. An oculomotor delayed-response task was used to examine the spatial memory functions of neurons in primate prefrontal cortex. Monkeys were trained to fixate a central spot during a brief presentation (0.5 s) of a peripheral cue and throughout a subsequent delay period (1-6 s), and then, upon the extinction of the fixation target, to make a saccadic eye movement to where the cue had been presented. Cues were usually presented in one of eight different locations separated by 45 degrees. This task thus requires monkeys to direct their gaze to the location of a remembered visual cue, controls the retinal coordinates of the visual cues, controls the monkey's oculomotor behavior during the delay period, and also allows precise measurement of the timing and direction of the relevant behavioral responses. 2. Recordings were obtained from 288 neurons in the prefrontal cortex within and surrounding the principal sulcus (PS) while monkeys performed this task. An additional 31 neurons in the frontal eye fields (FEF) region within and near the anterior bank of the arcuate sulcus were also studied. 3. Of the 288 PS neurons, 170 exhibited task-related activity during at least one phase of this task and, of these, 87 showed significant excitation or inhibition of activity during the delay period relative to activity during the intertrial interval. 4. Delay period activity was classified as directional for 79% of these 87 neurons in that significant responses only occurred following cues located over a certain range of visual field directions and were weak or absent for other cue directions. The remaining 21% were omnidirectional, i.e., showed comparable delay period activity for all visual field locations tested. Directional preferences, or lack thereof, were maintained across different delay intervals (1-6 s). 5. For 50 of the 87 PS neurons, activity during the delay period was significantly elevated above the neuron's spontaneous rate for at least one cue location; for the remaining 37 neurons only inhibitory delay period activity was seen. Nearly all (92%) neurons with excitatory delay period activity were directional and few (8%) were omnidirectional. Most (62%) neurons with purely inhibitory delay period activity were directional, but a substantial minority (38%) was omnidirectional. 6. Fifteen of the neurons with excitatory directional delay period activity also had significant inhibitory delay period activity for other cue directions. These inhibitory responses were usually strongest for, or centered about, cue directions roughly opposite those optimal for excitatory responses.(ABSTRACT TRUNCATED AT 400 WORDS)