Differential activity of prefrontal units during right and left delayed response trials

Working memory refers to the temporary retention of information that has just arrived to the senses or been retrieved from long-term memory. While internal representations of external stimuli have a natural tendency to decay, they can be kept “in mind” through the action of maintenance or rehearsal strategies and can be subjected to various operations that manipulate information in the service of ongoing behavior. Empirical studies of working memory using the tools of neuroscience, such as electrophysiological recordings in monkeys and functional neuroimaging in humans, have advanced our knowledge of the underlying neural mechanisms of working memory.

The prefrontal cortex plays a critical role in the temporal organization of behavior and language within the broad neurobiological framework of the perception–action (PA) cycle, the circular processing of information that regulates the adaptation of the organism to its environment. That temporal organizing role of the prefrontal cortex is supported by three major executive functions that constitute the essential dynamic components of the cognitive control of behavior and language: (1) executive attention, (2) working memory, and (3) decision-making. The three functions are teleonomic in that they have a critical future perspective toward goal or reward. In this chapter, after discussion of the PA cycle and of the physiological role of the prefrontal cortex in it, executive attention, working memory, and decision-making are empirically placed in both cycle and cortex with the available experimental evidence.

Microelectrode recordings of cortical activity in primates performing working memory tasks reveal some cortical neurons exhibiting sustained or graded persistent elevations in firing rate during the period in which sensory information is actively maintained in short-term memory. These neurons are called “memory cells”. Imaging and transcranial magnetic stimulation studies indicate that memory cells may arise from distributed cortical networks. Depending on the sensory modality of the memorandum in working memory tasks, neurons exhibiting memory-correlated patterns of firing have been detected in different association cortices including prefrontal cortex, and primary sensory cortices as well.

Here we elaborate on neurophysiological experiments that lead to our understanding of the neuromechanisms of working memory, and mainly discuss findings on widely distributed cortical networks involved in tactile working memory.

The representation of space and its function in the prefrontal cortex have been examined using a variety of behavioral tasks. Among them, since the delayed-response task requires the temporary maintenance of spatial information, this task has been used to examine the mechanisms of spatial representation. In addition, the concept of working memory to explain prefrontal functions has helped us to understand the nature and functions of space representation in the prefrontal cortex. The detailed analysis of delay-period activity observed in spatial working memory tasks has provided important information for understanding space representation in the prefrontal cortex. Directional delay-period activity has been shown to be a neural correlate of the mechanism for temporarily maintaining information and represent spatial information for the visual cue and the saccade. In addition, many task-related prefrontal neurons exhibit spatially selective activities. These neurons are also important components of spatial information processing. In fact, information flow from sensory-related neurons to motor-related neurons has been demonstrated, along with a change in spatial representation as the trial progresses. The dynamic functional interactions among neurons exhibiting different task-related activities and representing different aspects of information could play an essential role in information processing. In addition, information provided from other cortical or subcortical areas might also be necessary for the representation of space in the prefrontal cortex. To better understand the representation of space and its function in the prefrontal cortex, we need to understand the nature of functional interactions between the prefrontal cortex and other cortical and subcortical areas.

The ability to monitor one's own memory processes is an important feature of human cognition and is referred to as metamemory. Although several human neuropsychological and neuroimaging studies have been conducted on metamemory, the neural mechanism that underlies this cognitive function is still unknown due to a lack of neurobiological research using nonhuman animals. In the present study, we trained four macaque monkeys to perform an oculomotor working memory task that was designed to be suitable for various neurobiological approaches to metamemory. In this task, the monkeys were sometimes allowed to choose to either take or escape from a spatial working memory test (Choice condition) and sometimes forced to take the test (Test condition). The difficulty of the task was manipulated by varying the number of distractors. We used two criteria to determine whether the monkeys showed metamnemonic ability: (1) there should be a negative correlation between memory performance in the Test condition and the escape rate in the Choice condition, and (2) memory performance should be better in the Choice condition than in the Test condition. Three of the four monkeys fulfilled these criteria. In addition, the response times of one of these three monkeys provided additional evidence that it used metamnemonic ability. These results suggest that the present task can be a useful tool for investigating the neural mechanism of metamemory in monkeys. Neurobiological research on metamemory using primate models is necessary to understand human cognition, and our study contributes to progress in this research area.