Working memory in the prefrontal cortex

The prefrontal cortex participates in a variety of higher cognitive functions. The concept of working memory is now widely used to understand prefrontal functions. Neurophysiological studies have revealed that stimulus-selective delay-period activity is a neural correlate of the mechanism for temporarily maintaining information in working memory processes. The central executive, which is the master component of Baddeley’s working memory model and is thought to be a function of the prefrontal cortex, controls the performance of other components by allocating a limited capacity of memory resource to each component based on its demand. Recent neurophysiological studies have attempted to reveal how prefrontal neurons achieve the functions of the central executive. For example, the neural mechanisms of memory control have been examined using the interference effect in a dual-task paradigm. It has been shown that this interference effect is caused by the competitive and overloaded recruitment of overlapping neural populations in the prefrontal cortex by two concurrent tasks and that the information-processing capacity of a single neuron is limited to a fixed level, can be flexibly allocated or reallocated between two concurrent tasks based on their needs, and enhances behavioral performance when its allocation to one task is increased. Further, a metamemory task requiring spatial information has been used to understand the neural mechanism for monitoring its own operations, and it has been shown that monitoring the quality of spatial information represented by prefrontal activity is an important factor in the subject's choice and that the strength of spatially selective delay-period activity reflects confidence in decision-making. Although further studies are needed to elucidate how the prefrontal cortex controls memory resource and supervises other systems, some important mechanisms related to the central executive have been identified

Toward an understanding of the neural mechanisms underlying dual-task performance: Contribution of comparative approaches using animal models

The study of dual-task performance in human subjects has received considerable interest in cognitive neuroscience because it can provide detailed insights into the neural mechanisms underlying higher-order cognitive control. Despite many decades of research, our understanding of the neurobiological basis of dual-task performance is still limited, and some critical questions are still under debate. Recently, behavioral and neurophysiological studies of dual-task performance in animals have begun to provide intriguing evidence regarding how dual-task information is processed in the brain. In this review, we first summarize key evidence in neuroimaging and neuropsychological studies in humans and discuss possible reasons for discrepancies across studies. We then provide a comprehensive review of the literature on dual-task studies in animals and provide a novel working hypothesis that may reconcile the divergent results in human studies toward a unified view of the mechanisms underlying dual-task processing. Finally, we propose possible directions for future dual-task experiments in the framework of comparative cognitive neuroscience

ムメイシツ ジコ シゲキ ニ ヨリ キョウカサレタ シカクセイ ツイセキ カダイ スイコウチュウ ノ サル ゼントウ ゼンヤ ニューロン ノ オウトウ

京都大学0048新制・論文博士理学博士乙第4648号論理博第780号新制||理||404(附属図書館)UT51-57-E594(主査)教授 久保田 竸, 教授 室伏 靖子, 教授 大島 清学位規則第5条第2項該当Kyoto UniversityDFA

Thalamic mediodorsal nucleus and its participation in spatial working memory processes: comparison with the prefrontal cortex

Working memory is a dynamic neural system that includes processes for temporarily maintaining and processing information. Working memory plays a significant role in a variety of cognitive functions, such as thinking, reasoning, decision-making, and language comprehension. Although the prefrontal cortex (PFC) is known to play an important role in working memory, several lines of evidence indicate that the thalamic mediodorsal nucleus (MD) also participates in this process. While monkeys perform spatial working memory tasks, MD neurons exhibit directionally selective delay-period activity, which is considered to be a neural correlate for the temporary maintenance of information in PFC neurons. Studies have also shown that, while most MD neurons maintain prospective motor information, some maintain retrospective sensory information. Thus, the MD plays a greater role in prospective motor aspects of working memory processes than the PFC, which participates more in retrospective aspects. For the performance of spatial working memory tasks, the information provided by a sensory cue needs to be transformed into motor information to give an appropriate response. A population vector analysis using neural activities revealed that, although the transformation of sensory-to-motor information occurred during the delay period in both the PFC and the MD, PFC activities maintained sensory information until the late phase of the delay period, while MD activities initially represented sensory information but then started to represent motor information in the earlier phase of the delay period. These results indicate that long-range neural interactions supported by reciprocal connections between the MD and the PFC could play an important role in the transformation of maintained information in working memory processes

Physical Features of Visual Images Affect Macaque Monkey’s Preference for These Images

Animals exhibit different degrees of preference toward various visual stimuli. In addition, it has been shown that strongly preferred stimuli can often act as a reward. The aim of the present study was to determine what features determine the strength of the preference for visual stimuli in order to examine neural mechanisms of preference judgment. We used 50 color photographs obtained from the Flickr Material Database (FMD) as original stimuli. Four macaque monkeys performed a simple choice task, in which two stimuli selected randomly from among the 50 stimuli were simultaneously presented on a monitor and monkeys were required to choose either stimulus by eye movements. We considered that the monkeys preferred the chosen stimulus if it continued to look at the stimulus for an additional 6 s and calculated a choice ratio for each stimulus. Each monkey exhibited a different choice ratio for each of the original 50 stimuli. They tended to select clear, colorful and in-focus stimuli. Complexity and clarity were stronger determinants of preference than colorfulness. Images that included greater amounts of spatial frequency components were selected more frequently. These results indicate that particular physical features of the stimulus can affect the strength of a monkey’s preference and that the complexity, clarity and colorfulness of the stimulus are important determinants of this preference. Neurophysiological studies would be needed to examine whether these features of visual stimuli produce more activation in neurons that participate in this preference judgment

Opposing history effect of preceding decision and action in the free choice of saccade direction.

When we act voluntarily, we make a decision to do so prior to the actual execution. However, because of the strong tie between decision and action, it has been difficult to dissociate these two processes in an animal's free behavior. In the present study, we tried to characterize the differences in these processes on the basis of their unique history effect. Using simple eye movement tasks in which the direction of a saccade was either instructed by a computer or freely chosen by the subject, we found that the preceding decision and action had different effects on the animal's subsequent behavior. While choosing a direction (previous decision) produced a positive history effect that prompted the choice of the same saccade direction, making a saccadic response to a direction (previous action) produced a negative history effect that discouraged the monkey from choosing the same direction. This result suggests that the history effect in sequential behavior reported in previous studies was a mixture of these two different components. Future studies on decision-making need to consider the importance of the distinction between decision and action in animal behavior

Primate models of interference control

Interference control is the ability to protect ongoing cognitive processing from internal or environmental distraction. For an individual to achieve interference control appropriately, either a control mechanism to coordinate multiple processing streams, such as the central executive in working memory, a mechanism to flexibly allocate the cognitive resource with a limited capacity for performing each task, or both, are needed. Through the use of dual-task paradigms, animal studies have provided important information to elucidate the neural mechanisms of the central executive and the flexible allocation of cognitive resource. These animal studies should help to promote our understanding of the neural mechanisms of interference control

Thalamic mediodorsal nucleus and working memory.

Working memory is a dynamic neural system for temporarily maintaining and processing information. The prefrontal cortex (PFC) plays an important role in working memory. However, several evidences indicate that the thalamic mediodorsal nucleus (MD) also participates in working memory. Neurophysiological studies revealed that MD neurons exhibit sustained delay activity, which is considered to be a neural correlate of the temporary maintenance of information. Most MD neurons with delay activity represented information regarding motor responses, whereas some represented information regarding visual cues, suggesting that the MD participates more in prospective aspects of working memory, in contrast to the PFC, in which a minority participates in prospective aspects of working memory. A population vector analysis revealed that the transformation of sensory-to-motor information occurred during the earlier phase of the delay period in the MD compared with the PFC. These results indicate that reverberating neural circuits constructed by reciprocal connections between the MD and the PFC could be an important component for constructing prospective information in the PFC

Prefrontal cortex and neural mechanisms of executive function.

Executive function is a product of the coordinated operation of multiple neural systems and an essential prerequisite for a variety of cognitive functions. The prefrontal cortex is known to be a key structure for the performance of executive functions. To accomplish the coordinated operations of multiple neural systems, the prefrontal cortex must monitor the activities in other cortical and subcortical structures and control and supervise their operations by sending command signals, which is called top-down signaling. Although neurophysiological and neuroimaging studies have provided evidence that the prefrontal cortex sends top-down signals to the posterior cortices to control information processing, the neural correlate of these top-down signals is not yet known. Through use of the paired association task, it has been demonstrated that top-down signals are used to retrieve specific information stored in long-term memory. Therefore, we used a paired association task to examine the neural correlates of top-down signals in the prefrontal cortex. The preliminary results indicate that 32% of visual neurons exhibit pair-selectivity, which is similar to the characteristics of pair-coding activities in temporal neurons. The latency of visual responses in prefrontal neurons was longer than bottom-up signals but faster than top-down signals in inferior temporal neurons. These results suggest that pair-selective visual responses may be top-down signals that the prefrontal cortex provides to the temporal cortex, although further studies are needed to elucidate the neural correlates of top-down signals and their characteristics to understand the neural mechanism of executive control by the prefrontal cortex

Saccade-related activity in the prefrontal cortex: its role in eye movement control and cognitive functions

Prefrontal neurons exhibit saccade-related activity and pre-saccadic memory-related activity often encodes the directions of forthcoming eye movements, in line with demonstrated prefrontal contribution to flexible control of voluntary eye movements. However, many prefrontal neurons exhibit post-saccadic activity that is initiated well after the initiation of eye movement. Although post-saccadic activity has been observed in the frontal eye field, this activity is thought to be a corollary discharge from oculomotor centers, because this activity shows no directional tuning and is observed whenever the monkeys perform eye movements regardless of goal-directed or not. However, prefrontal post-saccadic activities exhibit directional tunings similar as pre-saccadic activities and show context dependency, such that post-saccadic activity is observed only when monkeys perform goal-directed saccades. Context-dependency of prefrontal post-saccadic activity suggests that this activity is not a result of corollary signals from oculomotor centers, but contributes to other functions of the prefrontal cortex. One function might be the termination of memory-related activity after a behavioral response is done. This is supported by the observation that the termination of memory-related activity coincides with the initiation of post-saccadic activity in population analyses of prefrontal activities. The termination of memory-related activity at the end of the trial ensures that the subjects can prepare to receive new and updated information. Another function might be the monitoring of behavioral performance, since the termination of memory-related activity by post-saccadic activity could be associated with informing the correctness of the response and the termination of the trial. However, further studies are needed to examine the characteristics of saccade-related activities in the prefrontal cortex and their functions in eye movement control and a variety of cognitive functions