Masamichi Sakagami

Encoding of behavioral significance of visual stimuli by primate prefrontal neurons: relation to relevant task conditions

Single-unit activity was recorded from the inferior dorsolateral prefrontal cortex of two monkeys while they performed a symmetrically rewarded go/no-go discrimination task. Three different task conditions were used in which the monkeys had to base their response on (1) the color, or (2) the shape, or (3) the position of a cue that was presented during fixation of a light spot. The colors of the fixation spot informed the monkeys which condition was relevant. The monkeys had to make an immediate release (go) or a delayed release (no-go) at the time of the fixation color change (imperative stimulus) depending on the currently relevant condition and the discriminative cue previously presented. The effect of changing the relevant condition on neuronal responses to the discriminative cue was analyzed. Out of 328 neurons tested in two or three conditions, 249 responded differentially at the cue period depending on the particular behavioral meaning of the stimulus (go or no-go) in at least one of the task conditions. This differential cue-period activity was examined across the different task conditions: the majority of neurons (111/154, 72%) showed such activity in all three conditions. In the remaining 43 neurons (28%) the differential activity was observed in two conditions (27/154, 18%) or in one condition (16/ 154, 10%). A few neurons (n = 7) showed feature-specific cue-period activity. In addition, 27 neurons displayed condition-dependent anticipatory activity prior to the cue onset. It is suggested that neurons in the inferior dorsolateral prefrontal cortex may participate in the conversion of sensory information from different visual channels into behavioral information (information on the upcoming response).

Feature-Based Anticipation of Cues that Predict Reward in Monkey Caudate Nucleus

A subset of caudate neurons fires before cues that instruct the monkey what he should do. To test the hypothesis that the anticipatory activity of such neurons depends on the context of stimulus-reward mapping, we examined their activity while the monkeys performed a memory-guided saccade task in which either the position or the color of a cue indicated presence or absence of reward. Some neurons showed anticipatory activity only when a particular position was associated with reward, while others fired selectively for color-reward associations. The functional segregation suggests that caudate neurons participate in feature-based anticipation of visual information that predicts reward. This neuronal code influences the general activity level in response to visual features without improving the quality of visual discrimination.

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.

Temporally Extended Dopamine Responses to Perceptually Demanding Reward-Predictive Stimuli

Midbrain dopamine neurons respond to reward-predictive stimuli. In the natural environment reward-predictive stimuli are often perceptually complicated. Thus, to discriminate one stimulus from another, elaborate sensory processing is necessary. Given that previous studies have used simpler types of reward-predictive stimuli, it has yet to be clear whether and, if so, how dopamine neurons obtain reward information from perceptually complicated stimuli. To investigate this, we recorded the activities of monkey dopamine neurons while they were performing discrimination between two coherent motion directions in random-dot motion stimuli. These coherent directions were paired with different magnitudes of reward. We found that dopamine neurons showed reward-predictive responses to random-dot motion stimuli. Moreover, dopamine neurons showed temporally extended activity correlated with changes in reward prediction (i.e., reward prediction error) from coarse to fine scales between initial motion detection and subsequent motion discrimination phases. Noticeably, dopamine reward-predictive responses became differential in a later phase than previously reported. This response pattern was consistent with the time course of processing required for the estimation of expected reward value that parallels the motion direction discrimination processing. The results demonstrate that dopamine neurons are able to reflect the reward value of perceptually complicated stimuli, and suggest that dopamine neurons use the moment-to-moment reward prediction associated with environmental stimuli to compute a reward prediction error.

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.

Functional role of the ventrolateral prefrontal cortex in decision making

To make deliberate decisions, we have to utilize detailed information about the environment and our internal states. The ventral visual pathway provides detailed information on object identity, including color and shape, to the ventrolateral prefrontal cortex (VLPFC). The VLPFC also receives motivational and emotional information from the orbitofrontal cortex and subcortical areas, and computes the behavioral significance of external events; this information can be used for elaborate decision making or design of goal-directed behavior. In this review, we discuss recent advances that are revealing the neural mechanisms that underlie the coding of behavioral significance in the VLPFC, and the functional roles of these mechanisms in decision making and action programming in the brain.

The hierarchical organization of decision making in the primate prefrontal cortex.

The prefrontal cortex plays an important role in making the association between sensory information and specific behavior. For example, in a complex stimulus response situation, such as the Wisconsin card sorting test, prefrontal patients show difficulty in making appropriate decisions. To understand the neural mechanisms, we recorded prefrontal cell activity while monkeys performed a go/no-go selective attention task where the subjects made a go or no-go response depending on the color or the motion direction of compound visual stimuli (moving colored dots). Groups of cells showed differential activity for go and no-go stimuli (go/no-go activity): some showed the activity either in the color or motion attending condition, and others showed the activity both in the color and motion conditions. Cells of shorter latencies, found mainly in the prefrontal subareas receiving visual input, showed go/no-go activity only when task demands necessitated that the monkeys attended to that cells preferred visual dimension. We also found cells with longer latencies in the motor-related periarcuate area that showed go/no-go activity regardless of the dimension attended. These results suggest that subareas in the prefrontal cortex play different roles in associating the sensory information with its behavioral meaning and are hierarchically organized to make appropriate decisions in complex tasks.

Reward prediction based on stimulus categorization in primate lateral prefrontal cortex

To adapt to changeable or unfamiliar environments, it is important that animals develop strategies for goal-directed behaviors that meet the new challenges. We used a sequential paired-association task with asymmetric reward schedule to investigate how prefrontal neurons integrate multiple already-acquired associations to predict reward. Two types of reward-related neurons were observed in the lateral prefrontal cortex: one type predicted reward independent of physical properties of visual stimuli and the other encoded the reward value specific to a category of stimuli defined by the task requirements. Neurons of the latter type were able to predict reward on the basis of stimuli that had not yet been associated with reward, provided that another stimulus from the same category was paired with reward. The results suggest that prefrontal neurons can represent reward information on the basis of category and propagate this information to category members that have not been linked directly with any experience of reward.

Behavioral inhibition and prefrontal cortex in decision-making

Every day we make innumerable decisions; some require no effort at all whereas others require considerable deliberation and weighing of various options. Despite the importance of decision-making in our lives and increased research interest, the specific neural mechanisms underlying decision-making remain unclear. We propose that the brain has at least two cortical pathways that independently generate a decision about appropriate behavior in given circumstances. These two pathways are extensions of the dorsal and ventral streams of the visual processing pathways. The parieto-premotor (extended dorsal) pathway makes decisions about motor actions in a largely autonomous and automatic fashion whereas the temporo-ventrolateral prefrontal (extended ventral) pathway is involved primarily in deliberate decisions and inhibitory control over behavior through the inhibitory function of the ventrolateral prefrontal cortex.

Spatial selectivity of go/no-go neurons in monkey prefrontal cortex

We examined single-unit activity in the inferior prefrontal cortex during a visual go/no-go discrimination task under maintained visual fixation. The monkeys had to base their response on either the color, shape, or position of a discriminative cue, and the relevant task condition was indicated by the color of the fixation spot. We analyzed the spatial selectivity of 128 go/no-go neurons showing a marked differential cue-period activity that depended on whether the stimulus signaled a go or no-go response. Most of these neurons (n = 106, 83%) showed asymmetry between their responses to stimuli in the contralateral and ipsilateral visual fields. Seventy-seven of these neurons had a contralateral preferential field, and 29 had an ipsilateral preferential field. These results show that in many inferior prefrontal neurons a degree of differentiation in their responses to go and no-go stimuli depends on the cue positions, and that the coding of behavioral meaning is carried out mainly in the contralateral hemisphere.