Mark J. Buckley

Optimal decision making and the anterior cingulate cortex

Learning the value of options in an uncertain environment is central to optimal decision making. The anterior cingulate cortex (ACC) has been implicated in using reinforcement information to control behavior. Here we demonstrate that the ACCs critical role in reinforcement-guided behavior is neither in detecting nor in correcting errors, but in guiding voluntary choices based on the history of actions and outcomes. ACC lesions did not impair the performance of monkeys (Macaca mulatta) immediately after errors, but made them unable to sustain rewarded responses in a reinforcement-guided choice task and to integrate risk and payoff in a dynamic foraging task. These data suggest that the ACC is essential for learning the value of actions.

Conflict-induced behavioural adjustment: a clue to the executive functions of the prefrontal cortex.

The behavioural adjustment that follows the experience of conflict has been extensively studied in humans, leading to influential models of executive-control adjustment. Recent studies have revealed striking similarities in conflict-induced behavioural adjustment between humans and monkeys, indicating that monkeys can provide a model to study the underlying neural substrates and mechanisms of such behaviour. These studies have advanced our knowledge about the role of different prefrontal brain regions, including the anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex (DLPFC), in executive-control adjustment and suggest a pivotal role for the DLPFC in the dynamic tuning of executive control and, consequently, in behavioural adaptation to changing environments.

Functional organization of the medial frontal cortex.

The anterior cingulate cortex (ACC) and adjacent areas of the medial frontal cortex (MFC) have been implicated in monitoring behaviour and in detecting errors. Recent evidence, however, suggests that the ACC not only registers the occurrence of errors but also represents other aspects of the reinforcement history that are crucial for guiding behaviour. Other studies raise the possibility that dorsal MFC areas not only monitor behaviour but also actually control response selection, particularly when the task in hand is changing. Many decisions are made in social contexts and their chances of success depend on what other individuals are doing. Evaluation of other individuals is therefore crucial for effective action selection, and some ACC regions are implicated in this process.

Frontal Cortex Subregions Play Distinct Roles in Choices between Actions and Stimuli

The orbitofrontal cortex (OFC) has been implicated in reinforcement-guided decision making, error monitoring, and the reversal of behavior in response to changing circumstances. The anterior cingulate cortex sulcus (ACCS), however, has also been implicated in similar aspects of behavior. Dissociating the unique functions of these areas would improve our understanding of the decision-making process. The effect of selective OFC lesions on how monkeys used the history of reinforcement to guide choices of either particular actions or particular stimuli was studied and compared with the effects of ACCS lesions. Both lesions disrupted decision making, but their effects were differentially modulated by the dependence on action– or stimulus–value contingencies. OFC lesions caused a deficit in stimulus but not action selection, whereas ACCS lesions had the opposite effect, disrupting action but not stimulus selection. Furthermore, OFC lesions that have previously been found to impair decision making when deterministic stimulus–reward contingencies are switched were found to cause a more general learning impairment in more naturalistic situations in which reward was stochastic. Both OFC and ACCS are essential for reinforcement-guided decision making rather than just error monitoring or behavioral reversal. The OFC and ACCS are both, however, more concerned with learning and making decisions, but their roles in selecting between stimulus and action values are distinct.

A Role for the Macaque Anterior Cingulate Gyrus in Social Valuation

Complex human social interaction is disrupted when the frontal lobe is damaged in disease, and in extreme cases patients are described as having acquired sociopathy. We compared, in macaques, the effects of lesions in subdivisions of the anterior cingulate and the orbitofrontal cortices believed to be anatomically homologous to those damaged in such patients. We show that the anterior cingulate gyrus in male macaques is critical for normal patterns of social interest in other individual male or female macaques. Conversely, the orbitofrontal cortex lesion had a marked effect only on responses to mildly fear-inducing stimuli. These results suggest that damage to the anterior cingulate gyrus may be the cause of changes in social interaction seen after frontal lobe damage.

Dissociable components of rule-guided behavior depend on distinct medial and prefrontal regions.

Card Sorting Monkeys Single-neuron studies in primates help to establish a detailed understanding of cognitive processing and to provide an experimental base for understanding the cognitive deficits incurred by patients who have suffered damage to areas of the brain. Buckley et al. (p. 52) present the results of an intensive behavioral analysis of a group of monkeys bearing lesions to distinct areas of the prefrontal lobe. The Wisconsin Card Sorting Task is widely used in the clinic to assess the flexible learning of abstract rules. In the primates, a functional dissociation was observed across three regions: the principal sulcus, the orbitofrontal cortex, and the anterior cingulate cortex. This set of results contributes to the ongoing discussion of goal-directed behavior and serves to bridge neuropsychological studies in human patients and neurophysiological studies in primates. A card-sorting task shows that three distinct regions of the monkey prefrontal cortex perform distinct cognitive functions. Much of our behavior is guided by rules. Although human prefrontal cortex (PFC) and anterior cingulate cortex (ACC) are implicated in implementing rule-guided behavior, the crucial contributions made by different regions within these areas are not yet specified. In an attempt to bridge human neuropsychology and nonhuman primate neurophysiology, we report the effects of circumscribed lesions to macaque orbitofrontal cortex (OFC), principal sulcus (PS), superior dorsolateral PFC, ventrolateral PFC, or ACC sulcus, on separable cognitive components of a Wisconsin Card Sorting Test (WCST) analog. Only the PS lesions impaired maintenance of abstract rules in working memory; only the OFC lesions impaired rapid reward-based updating of representations of rule value; the ACC sulcus lesions impaired active reference to the value of recent choice-outcomes during rule-based decision-making.

Separate value comparison and learning mechanisms in macaque medial and lateral orbitofrontal cortex.

Uncertainty about the function of orbitofrontal cortex (OFC) in guiding decision-making may be a result of its medial (mOFC) and lateral (lOFC) divisions having distinct functions. Here we test the hypothesis that the mOFC is more concerned with reward-guided decision making, in contrast with the lOFCs role in reward-guided learning. Macaques performed three-armed bandit tasks and the effects of selective mOFC lesions were contrasted against lOFC lesions. First, we present analyses that make it possible to measure reward-credit assignment—a crucial component of reward-value learning—independently of the decisions animals make. The mOFC lesions do not lead to impairments in reward-credit assignment that are seen after lOFC lesions. Second, we examined how the reward values of choice options were compared. We present three analyses, one of which examines reward-guided decision making independently of reward-value learning. Lesions of the mOFC, but not the lOFC, disrupted reward-guided decision making. Impairments after mOFC lesions were a function of the multiple option contexts in which decisions were made. Contrary to axiomatic assumptions of decision theory, the mOFC-lesioned animals’ value comparisons were no longer independent of irrelevant alternatives.

Impairment of visual object-discrimination learning after perirhinal cortex ablation.

Eight cynomolgus monkeys learned preoperatively 20 concurrent visual discriminations between pairs of colored shapes presented on a touch screen with 24-hr intertrial intervals. Three then received bilateral perirhinal cortex ablation, and 5 remained controls. The ablated monkeys were severely impaired in reacquiring the preoperatively acquired set, whereas postoperative learning of 20 new discriminations was not significantly affected. The task was then made more difficult. First, the number of foils from which the stimulus had to be selected was increased to 2, 4, 7, and then 14. Second, larger sets of 40, 80, and 160 problems were presented. Both manipulations revealed some significant but relatively mild impairments in the monkeys with ablations. It is suggested that perirhinal cortex ablation impairs the monkeys capacity to identify individual objects, which leads to deficits in both visual-object recognition memory and discrimination learning.

Perirhinal cortex ablation impairs configural learning and paired–associate learning equally

Combined damage to the perirhinal and entorhinal cortex has been implicated in the formation of stimulus-stimulus associative memories. We show in this article that relative to three normal controls three cynomolgus monkeys with ablations restricted to the perirhinal cortex were impaired on a visual paired associate learning task in which subjects had to learn which of two visual stimuli were associated with a cue stimulus. The subjects with perirhinal cortex ablations also showed an impairment of a similar magnitude on a visual configural learning task in which they had to learn which of two configurations of visual stimuli were associated with food-reward. The stimuli in both tasks were comprised of alphanumeric characters presented upon a touch-screen. Both groups made fewer errors on the configural learning task than on the paired associate learning task. We suggest that performance on both tasks relies critically on the perirhinal cortex due to the specialization of the perirhinal cortex in processing knowledge about objects. We argue that the specializations of this system and of other memory systems such as the hippocampal-fornix spatial/episodic memory system, are conferred by the specialization of their anatomical connections to other structures. We reject the notion that there are specific memory processes such as the hippocampal based configural associative system that was proposed to be critical for configural associative learning.

Perirhinal cortical contributions to object perception

The traditional theory of the medial temporal lobe (MTL) memory system asserts that the primate MTL (hippocampus, perirhinal, entorhinal and parahippocampal cortices) is exclusively involved in consolidating declarative memories. However, several recent reports have directly challenged this dogma by arguing that MTL structures also contribute to perception. Controversy remains as many of the behavioural tasks used have confounded memory with perception. We review the evidence here and highlight new studies in humans and macaques that indicate a perceptual role for MTL in the absence of such confounds. We argue that the challenge to MTL memory system theory is substantiated and that the implications are considerable, namely that most psychologists and neuroscientists have held a fundamentally flawed view of how memory is implemented in the brain.