Masataka Watanabe

Frontal units of the monkey coding the associative significance of visual and auditory stimuli.

SummaryTwo monkeys were trained on both visual and auditory association tasks. Single unit activity of the frontal (prefrontal and post-arcuate premotor) cortex was recorded in these monkeys to investigate the convergence of visual and auditory inputs and to examine whether the frontal units are involved in coding the meaning (associative significance) of the stimulus, independent of its modality. A total of 289 units showed changes in firing rate after the cue presentation on the visual and/or auditory tasks and were examined on both modalities of tasks, 175 of them showing differential activity in relation to either the associative significance and/or physical properties of the visual and/or auditory cues. Of the 289 units, 136 (47.0%) were responsive only to the visual cue (76 of them showing cue-related differential activity), 13 units (4.5%) only to the auditory cue (6 of them showing cue-related differential activity) and the remaining 140 units (48.5%) to both modalities of cues (18 of them showing visual, 7 of them showing auditory and 68 showing both modalities of cue-related differential activity). Fifty of the 68 bimodal differential units showed changes in firing in relation to the associative significance of both modalities of cues independent of the cues physical properties, and are considered to be involved in the crossmodal coding of the associative significance of the stimulus. The proportion of bimodal differential units was higher in the pre- and post-arcuate areas than in the principalis and inferior convexity areas of the frontal cortex. The results indicate that some frontal units participate in the crossmodal coding of the associative significance of the stimulus independent of its physical properties, and most frontal units play different roles depending on the modality of the stimulus.

Functional Specialization of the Primate Frontal Cortex during Decision Making

Economic theories of decision making are based on the principle of utility maximization, and reinforcement-learning theory provides computational algorithms that can be used to estimate the overall reward expected from alternative choices. These formal models not only account for a large range of behavioral observations in human and animal decision makers, but also provide useful tools for investigating the neural basis of decision making. Nevertheless, in reality, decision makers must combine different types of information about the costs and benefits associated with each available option, such as the quality and quantity of expected reward and required work. In this article, we put forward the hypothesis that different subdivisions of the primate frontal cortex may be specialized to focus on different aspects of dynamic decision-making processes. In this hypothesis, the lateral prefrontal cortex is primarily involved in maintaining the state representation necessary to identify optimal actions in a given environment. In contrast, the orbitofrontal cortex and the anterior cingulate cortex might be primarily involved in encoding and updating the utilities associated with different sensory stimuli and alternative actions, respectively. These cortical areas are also likely to contribute to decision making in a social context.

Influences of Rewarding and Aversive Outcomes on Activity in Macaque Lateral Prefrontal Cortex

Both appetitive and aversive outcomes can reinforce animal behavior. It is not clear, however, whether the opposing kinds of reinforcers are processed by specific or common neural mechanisms. To investigate this issue, we studied macaque monkeys that performed a memory-guided saccade task for three different outcomes, namely delivery of liquid reward, avoidance of air puff, and feedback sound only. Animals performed the task best in rewarded trials, intermediately in aversive trials, and worst in sound-only trials. Most task-related activity in lateral prefrontal cortex was differentially influenced by the reinforcers. Aversive avoidance had clear effects on some prefrontal neurons, although the effects of rewards were more common. We also observed neurons modulated by both positive and negative reinforcers, reflecting reinforcement or attentional processes. Our results demonstrate that information about positive and negative reinforcers is processed differentially in prefrontal cortex, which could contribute to the role of this structure in goal-directed behavior.

Role of anticipated reward in cognitive behavioral control

The lateral prefrontal cortex (LPFC), which is important for higher cognitive activity, is also concerned with motivational operations; this is exemplified by its activity in relation to expectancy of rewards. In the LPFC, motivational information is integrated with cognitive information, as demonstrated by the enhancement of working-memory-related activity by reward expectancy. Such activity would be expected to induce changes in attention and, subsequently, to modify behavioral performance. Recently, the effects of motivation and emotion on neural activities have been examined in several areas of the brain in relation to cognitive-task performance. Of these areas, the LPFC seems to have the most important role in adaptive goal-directed behavior, by sending top-down attention-control signals to other areas of the brain.

Integration of cognitive and motivational information in the primate lateral prefrontal cortex.

Abstract:u2002 The prefrontal cortex (PFC), particularly the lateral prefrontal cortex (LPFC), has an important role in cognitive information processing. The area receives projections from sensory association cortices and sends outputs to motor‐related areas. Neurons in LPFC code the behavioral significance of stimuli, which can be abstract precursors for complex motor commands and are structured hierarchically. Loss of these neurons leads to a lack of flexibility in decision making, such as seen in stereotyped behaviors. However, to make more appropriate decisions the code for behavioral significance has to reflect the subjects own desires and demands. Indeed, LPFC has connections with reward‐related areas, such as the orbitofrontal cortex (OFC), basal ganglia, and medial prefrontal cortex. Recently, many studies have reported reward modulation of neural codes of behavioral significance. Using an asymmetric reward paradigm, we can investigate the functional specificity of LPFC neurons that code both cognitive information and motivational information. In this review, we will discuss details of neuronal properties of LPFC neurons from the viewpoints of cognitive information processing and motivational information processing, and the question of how these two pieces of information are integrated. Abstract coding and contextual representations in the cognitive information processing are functional characteristics of LPFC. Such functional specificity in LPFC cognitive processes is supported by a long‐term scale of reward history in the motivational information processing. The integration enables us to make an elaborate decision with respect to goal‐directed behavior in complex circumstances.

Default Mode of Brain Activity Demonstrated by Positron Emission Tomography Imaging in Awake Monkeys: Higher Rest-Related than Working Memory-Related Activity in Medial Cortical Areas

Human neuroimaging studies have demonstrated the presence of a “default system” in the brain, which shows a “default mode of brain activity,” i.e., greater activity during the resting state than during an attention-demanding cognitive task. The default system mainly involves the medial prefrontal and medial parietal areas, including the anterior and posterior cingulate cortex. It has been proposed that this default activity is concerned with internal thought processes. Recently, it has been indicated that chimpanzees show high metabolic levels in these medial brain areas during rest. Correlated low-frequency spontaneous activity as measured by functional magnetic resonance imaging was observed between the medial parietal and medial prefrontal areas in the anesthetized monkey. However, there have been few attempts to demonstrate a default system that shows task-induced deactivation in nonhuman primates. We conducted a positron emission tomography study with [15O]H2O to demonstrate a default mode of brain activity in the awake monkey sitting on a primate chair. Macaque monkeys showed higher level of regional blood flow in these medial brain areas as well as lateral and orbital prefrontal areas during rest compared with that under a working memory task, suggesting the existence of internal thought processes in the monkey. However, during rest in the monkey, the highest level of blood flow relative to that in other brain regions was observed not in the default system but in the dorsal striatum, suggesting that regions with the highest cerebral blood flow during rest may differ depending on the resting condition and/or species.

Prefrontal Neurons Represent Winning and Losing during Competitive Video Shooting Games between Monkeys

Humans and animals must work to support their survival and reproductive needs. Because resources are limited in the natural environment, competition is inevitable, and competing successfully is vitally important. However, the neuronal mechanisms of competitive behavior are poorly studied. We examined whether neurons in the lateral prefrontal cortex (LPFC) showed response sensitivity related to a competitive game. In this study, monkeys played a video shooting game, either competing with another monkey or the computer, or playing alone without a rival. Monkeys performed more quickly and more accurately in the competitive than in the noncompetitive games, indicating that they were more motivated in the competitive than in the noncompetitive games. LPFC neurons showed differential activity between the competitive and noncompetitive games showing winning- and losing-related activity. Furthermore, activities of prefrontal neurons differed depending on whether the competition was between monkeys or between the monkey and the computer. These results indicate that LPFC neurons may play an important role in monitoring the outcome of competition and enabling animals to adapt their behavior to increase their chances of obtaining a reward in a socially interactive environment.

Functional significance of delay-period activity of primate prefrontal neurons in relation to spatial working memory and reward/omission-of-reward expectancy

The lateral prefrontal cortex (LPFC) is important in cognitive control. During the delay period of a working memory (WM) task, primate LPFC neurons show sustained activity that is related to retaining task-relevant cognitive information in WM. However, it has not yet been determined whether LPFC delay neurons are concerned exclusively with the cognitive control of WM task performance. Recent studies have indicated that LPFC neurons also show reward and/or omission-of-reward expectancy-related delay activity, while the functional relationship between WM-related and reward/omission-of-reward expectancy-related delay activity remains unclear. To clarify the functional significance of LPFC delay-period activity for WM task performance, and particularly the functional relationship between these two types of activity, we examined individual delay neurons in the primate LPFC during spatial WM (delayed response) and non-WM (reward–no-reward delayed reaction) tasks. We found significant interactions between these two types of delay activity. The majority of the reward expectancy-related neurons and the minority of the omission-of-reward expectancy-related neurons were involved in spatial WM processes. Spatial WM-related neurons were more likely to be involved in reward expectancy than in omission-of-reward expectancy. In addition, LPFC delay neurons observed during the delayed response task were not concerned exclusively with the cognitive control of task performance; some were related to reward/omission-of-reward expectancy but not to WM, and many showed more memory-related activity for preferred rewards than for less-desirable rewards. Since employing a more preferred reward induced better task performance in the monkeys, as well as enhanced WM-related neuronal activity in the LPFC, the principal function of the LPFC appears to be the integration of cognitive and motivational operations in guiding the organism to obtain a reward more effectively.

Reward Expectancy-Related Prefrontal Neuronal Activities: Are They Neural Substrates of “Affective” Working Memory?

Primate prefrontal delay neurons are involved in retaining task-relevant cognitive information in working memory (WM). Recent studies have also revealed primate prefrontal delay neurons that are related to reward/omission-of-reward expectancy. Such reward-related delay activities might constitute affective WM (Davidson, 2002). Affective and cognitive WM are both concerned with representing not what is currently being presented, but rather what was presented previously or might be presented in the future. However, according to the original and widely accepted definition, WM is the temporary storage and manipulation of information for complex cognitive tasks. Reward/omission-of-reward expectancy-related neuronal activity is neither prerequisite nor essential for accurate task performance; thus, such activity is not considered to comprise the neural substrates of WM. Also, affective WM might not be an appropriate usage of the term WM. We propose that WM- and reward/omission-of-reward expectancy-related neuronal activity are concerned with representing which response should be performed in order to attain a goal (reward) and the goal of the response, respectively. We further suggest that the prefrontal cortex (PFC) plays a crucial role in the integration of cognitive (for example, WM-related) and motivational (for example, reward expectancy-related) operations for goal-directed behaviour. The PFC could then send this integrated information to other brain areas to control the behaviour.

Domain-related differentiation of working memory in the Japanese macaque (Macaca fuscata) frontal cortex: a positron emission tomography study

The lateral prefrontal cortex (LPFC) is important for working memory (WM) task performance. Neuropsychological and neurophysiological studies in monkeys suggest that the lateral prefrontal cortex is functionally segregated based on the working memory domain (spatial vs. non‐spatial). However, this is not supported by most human neuroimaging studies, and the discrepancy might be due to differences in methods and/or species (monkey neuropsychology/physiology vs. human neuroimaging). We used positron emission topography to examine the functional segregation of the lateral prefrontal cortex of Japanese macaques (Macaca fuscata) that showed near 100% accuracy on spatial and non‐spatial working memory tasks. Compared with activity during the non‐working memory control tasks, the dorsolateral prefrontal cortex (DLPFC) was more active during the non‐spatial, but not during the spatial, working memory task, although a muscimol microinjection into the dorsolateral prefrontal cortex significantly impaired the performance of both working memory tasks. A direct comparison of the brain activity between the two working memory tasks revealed no differences within the lateral prefrontal cortex, whereas the premotor area was more active during the spatial working memory task. Comparing the delay‐specific activity, which did not include task‐associated stimulus/response‐related activity, revealed more spatial working memory‐related activity in the posterior parietal and premotor areas, and more non‐spatial working memory‐related activity in the dorsolateral prefrontal cortex and hippocampus. These results suggest that working memory in the monkey brain is segregated based on domain, not within the lateral prefrontal cortex but rather between the posterior parietal‐premotor areas and the dorsolateral prefrontal‐hippocampus areas.