Morphine exposure modulates dimensional bias and set formation in anthropoids.

Humans demonstrate significant behavioural advantages with particular perceptual dimensions (such as colour or shape) and when the relevant dimension is repeated in consecutive trials. These dimension-related behavioural modulations are significantly altered in neuropsychological and addiction disorders; however, their underlying mechanisms remain unclear. Here, we studied whether these behavioural modulations exist in other trichromatic primate species and whether repeated exposure to opioids influences them. In a target detection task where the target-defining dimension (colour or shape) changed trial by trial, humans exhibited shorter response time (RT) and smaller event-related electrodermal activity with colour dimension; however, macaque monkeys had shorter RT with shape dimension. Although the dimensional biases were in the opposite directions, both species were faster when the relevant dimension was repeated, compared with conditions when it changed, across consecutive trials. These indicate that both species formed dimensional sets and that resulted in a significant 'switch cost'. Scheduled and repeated exposures to morphine, which is analogous to its clinical and recreational use, significantly augmented the dimensional bias in monkeys and also changed the switch cost depending on the relevant dimension. These cognitive effects occurred when monkeys were in abstinence periods (not under acute morphine effects) but expressing significant morphine-induced conditioned place preference. These findings indicate that significant dimensional biases and set formation are evolutionarily preserved in humans' and monkeys' cognition and that repeated exposure to morphine interacts with their manifestation. Shared neural mechanisms might be involved in the long-lasting effects of morphine and expression of dimensional biases and set formation in anthropoids.

Dissociable effects of music and white noise on conflict-induced behavioral adjustments.

Auditory stimuli, encompassing a continually expanding collection of musical genres and sonic hues, present a safe and easily administrable therapeutic option for alleviating cognitive deficits associated with neuropsychological disorders, but their effects on executive control are yet to be completely understood. To better understand how the processing of certain acoustic properties can influence conflict processing, we had a large of cohort of undergraduate students complete the Stroop colour and word test in three different background conditions: classical music, white noise, and silence. Because of pandemic guidelines and the necessity to run the experiment remotely, participants also completed the Wisconsin card sorting test (WCST), so that the reliability and consistency of acquired data could be assessed. We found that white noise, but not classical music increased the response time difference between congruent (low conflict) and incongruent (high conflict) trials (conflict cost), hence impairing performance. Results from the WCST indicated that home-based data collection was reliable, replicating a performance bias reported in our previous laboratory-based experiments. Both the auditory stimuli were played at a similar intensity, thus their dissociable effects may have resulted from differing emotional responses within participants, where white noise, but not music elicited a negative response. Integrated with previous literature, our findings indicate that outside of changes in tempo and valence, classical music does not affect cognitive functions associated with conflict processing, whilst white noise impairs these functions in a manner similar to other stressors, and hence requires further research before its implementation into neuropsychiatric care.

Dynamic modulation of inhibition ability following repeated exposures to morphine in macaque monkey.

BACKGROUND: Deficits in cognitive control, particularly inhibition ability, play crucial roles in susceptibility, progress, and relapse to opioid addiction. However, it is unclear when and how such deficits develop and interact with repeated exposures to prescribed opioids. AIM: Using macaque monkey (Macaca mulatta), as an animal model with high translational merits in cognitive neuroscience, we tried to delineate alterations of inhibition ability in the course of repeated exposures to morphine. METHODS: Monkeys were trained to perform stop-signal task and then we closely monitored their inhibition ability before exposure, after initial exposure, and following repeated exposures to morphine when they experienced abstinent periods. We also assessed morphine-induced conditioned place preference (CPP) in these monkeys to monitor the long-lasting effects of morphine on other behaviors. RESULTS: Compared to the baseline level, monkeys' inhibition ability was significantly enhanced after initial exposure to morphine (early phase); however, it became significantly attenuated after repeated exposures (late phase). These alterations occurred while monkeys consistently expressed the morphine-induced CPP over the course of morphine exposure. CONCLUSIONS: Our findings indicate that repeated and scheduled exposures to morphine, which is akin to its clinical and recreational use, lead to dynamic alterations in primates' cognitive control depending on the extent of exposure. Enhancement of inhibition after limited exposure might provide opportunities to intervene and prevent the progress and culmination of opioid addiction, which is characterized by disinhibited drug-seeking and consumption.

Dimension of visual information interacts with working memory in monkeys and humans.

Humans demonstrate behavioural advantages (biases) towards particular dimensions (colour or shape of visual objects), but such biases are significantly altered in neuropsychological disorders. Recent studies have shown that lesions in the prefrontal cortex do not abolish dimensional biases, and therefore suggest that such biases might not depend on top-down prefrontal-mediated attention and instead emerge as bottom-up processing advantages. We hypothesised that if dimensional biases merely emerge from an enhancement of object features, the presence of visual objects would be necessary for the manifestation of dimensional biases. In a specifically-designed working memory task, in which macaque monkeys and humans performed matching based on the object memory rather than the actual object, we found significant dimensional biases in both species, which appeared as a shorter response time and higher accuracy in the preferred dimension (colour and shape dimension in humans and monkeys, respectively). Moreover, the mnemonic demands of the task influenced the magnitude of dimensional bias. Our findings in two primate species indicate that the dichotomy of top-down and bottom-up processing does not fully explain the emergence of dimensional biases. Instead, dimensional biases may emerge when processed information regarding visual object features interact with mnemonic and executive functions to guide goal-directed behaviour.

Investigating the sex-dependent effects of prefrontal cortex stimulation on response execution and inhibition.

Context-dependent execution or inhibition of a response is an important aspect of executive control, which is impaired in neuropsychological and addiction disorders. Transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC) has been considered a remedial approach to address deficits in response control; however, considerable variability has been observed in tDCS effects. These variabilities might be related to contextual differences such as background visual-auditory stimuli or subjects' sex. In this study, we examined the interaction of two contextual factors, participants' sex and background acoustic stimuli, in modulating the effects of tDCS on response inhibition and execution. In a sham-controlled and cross-over (repeated-measure) design, 73 participants (37 females) performed a Stop-Signal Task in different background acoustic conditions before and after tDCS (anodal or sham) was applied over the DLPFC. Participants had to execute a speeded response in Go trials but inhibit their response in Stop trials. Participants' sex was fully counterbalanced across all experimental conditions (acoustic and tDCS). We found significant practice-related learning that appeared as changes in indices of response inhibition (stop-signal reaction time and percentage of successful inhibition) and action execution (response time and percentage correct). The tDCS and acoustic stimuli interactively influenced practice-related changes in response inhibition and these effects were uniformly seen in both males and females. However, the effects of tDCS on response execution (percentage of correct responses) were sex-dependent in that practice-related changes diminished in females but heightened in males. Our findings indicate that participants' sex influenced the effects of tDCS on the execution, but not inhibition, of responses.

Dimensional bias and adaptive adjustments in inhibitory control of monkeys.

Humans and macaque monkeys, performing a Wisconsin Card Sorting Test (WCST), show a significant behavioral bias to a particular sensory dimension (e.g. color or shape); however, lesions in prefrontal cortical regions do not abolish the dimensional biases in monkeys and, therefore, it has been proposed that these biases emerge in earlier stages of visual information processing. It remains unclear whether such dimensional biases are unique to the WCST, in which attention-shifting between dimensions are required, or affect other aspects of executive functions such as 'response inhibition' and 'error-induced behavioral adjustments'. To address this question, we trained six monkeys (Macaca mulatta) to perform a stop-signal task in which they had to inhibit their response when an instruction for inhibition was given by changing the color or shape of a visual stimulus. Stop Signal Reaction Time (SSRT) is an index of inhibitory processes. In all monkeys, SSRT was significantly shorter, and the probability of a successful inhibition was significantly higher, when a change in the shape dimension acted as the stop-cue. Humans show a response slowing following a failure in response inhibition and also adapt a proactive slowing after facing demands for response inhibition. We found such adaptive behavioral adjustments, with the same pattern, in monkeys' behavior; however, the dimensional bias did not modulate them. Our findings, showing dimensional bias in monkey, with the same pattern, in two different executive control tasks support the hypothesis that the bias to shape dimension emerges in early stages of visual information processing.

Color-hierarchies in executive control of monkeys' behavior.

Processing advantages for particular colors (color-hierarchies) influence emotional regulation and cognitive functions in humans and manifest as an advantage of the red color, compared with the green color, in triggering response inhibition but not in response execution. It remains unknown how such color-hierarchies emerge in human cognition and whether they are the unique properties of human brain with advanced trichromatic vision. Dominant models propose that color-hierarchies are formed as experience-dependent learning that associates various colors with different human-made conventions and concepts (e.g., traffic lights). We hypothesized that if color-hierarchies modulate cognitive functions in trichromatic nonhuman primates, it would indicate a preserved neurobiological basis for such color-hierarchies. We trained six macaque monkeys to perform cognitive tasks that required behavioral control based on colored cues. Color-hierarchies significantly influenced monkeys' behavior and appeared as an advantage of the red color, compared to the green, in triggering response inhibition but not response execution. For all monkeys, the order of color-hierarchies, in response inhibition and also execution, was similar to that in humans. In addition, the cognitive effects of color-hierarchies were not limited to the trial in which the colored cues were encountered but also persisted in the following trials in which there was no colored cue on the visual scene. These findings suggest that color-hierarchies are not resulting from association of colors with human-made conventions and that simple processing advantage in retina or early visual pathways does not explain the cognitive effects of color-hierarchies. The discovery of color-hierarchies in cognitive repertoire of monkeys indicates that although the evolution of humans and monkeys diverged in about 25 million years ago, the color-hierarchies are evolutionary preserved, with the same order, in trichromatic primates and exert overarching effects on the executive control of behavior.

The Role of Primate Prefrontal Cortex in Bias and Shift Between Visual Dimensions.

Imaging and neural activity recording studies have shown activation in the primate prefrontal cortex when shifting attention between visual dimensions is necessary to achieve goals. A fundamental unanswered question is whether representations of these dimensions emerge from top-down attentional processes mediated by prefrontal regions or from bottom-up processes within visual cortical regions. We hypothesized a causative link between prefrontal cortical regions and dimension-based behavior. In large cohorts of humans and macaque monkeys, performing the same attention shifting task, we found that both species successfully shifted between visual dimensions, but both species also showed a significant behavioral advantage/bias to a particular dimension; however, these biases were in opposite directions in humans (bias to color) versus monkeys (bias to shape). Monkeys' bias remained after selective bilateral lesions within the anterior cingulate cortex (ACC), frontopolar cortex, dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), or superior, lateral prefrontal cortex. However, lesions within certain regions (ACC, DLPFC, or OFC) impaired monkeys' ability to shift between these dimensions. We conclude that goal-directed processing of a particular dimension for the executive control of behavior depends on the integrity of prefrontal cortex; however, representation of competing dimensions and bias toward them does not depend on top-down prefrontal-mediated processes.

Negative Emotional Stimuli Enhance Conflict Resolution Without Altering Arousal.

In our daily life, we frequently need to make decisions between competing behavioral options while we are exposed to various contextual factors containing emotional/social information. We examined how changes in emotional/arousal state influence resolving conflict between behavioral rules. Visual stimuli with emotional content (positive, negative and neutral) and music (High/Low tempo), which could potentially alter emotional/arousal states, were included in the task context while participants performed the Wisconsin Card Sorting Test (WCST). The WCST requires the application of abstract matching rules, to resolve conflict between competing behavioral options. We found that conflict influenced both accuracy and response time (RT) in implementing rules. Measuring event-related autonomic responses indicated that these behavioral effects were accompanied by concomitant alterations in arousal levels. Performance in the WCST was modulated by the emotional content of visual stimuli and appeared as a faster response and higher accuracy when trials commenced with negative emotional stimuli. These effects were dependent on the level of conflict but were not accompanied by changes in arousal levels. Here, we report that visual stimuli with emotional content influence conflict processing without trial-by-trial changes in arousal level. Our findings indicate intricate interactions between emotional context and various aspects of executive control such as conflict resolution and suggest that these interactions are not necessarily mediated through alterations in arousal level.

Interaction of music and emotional stimuli in modulating working memory in macaque monkeys.

Background music is one of the most frequently encountered contextual factors that affect cognitive and emotional functions in humans. However, it is still unclear whether music induces similar effects in nonhuman primates. Answering this question might bring insight to the long-lasting question regarding the ability of nonhuman primates in perceiving and dissociating music from other nonmusical acoustic information. In the present study, macaque monkeys were trained to perform a working memory task that required matching visual stimuli. These stimuli had different emotional content (neutral, negative, and positive). Monkeys performed the task within different background acoustic conditions (music, same-intensity noise, and silence). We hypothesized that the auditory stimuli might interact with emotional information of visual stimuli and modulate monkeys' performance. Furthermore, if the effects of music and noise on monkeys' behavioral measures differ it would mean that monkeys perceived and processed music differently. We found that, monkeys committed more errors and were slower when they encountered stimuli with negative or positive emotional content. In the presence of music, the influence of emotional stimuli on monkeys' performance significantly differed from those of the neutral stimuli, however, in the presence of noise, the effects of emotional stimuli on monkeys' performance were not distinguishable. The dissociable effects of music and noise on monkeys' performance show that the effects of emotional stimuli were dependent on the background acoustic conditions. Our findings indicate that background music and the same-intensity noise were differentially perceived by monkeys and influenced their cognitive functions.

Interaction of task-related learning and transcranial direct current stimulation of the prefrontal cortex in modulating executive functions.

The effects of transcranial direct-current stimulation (tDCS) on cognitive functions, such as response inhibition, might be mediated through plastic changes within the prefrontal cortex. Previous studies have also confirmed learning-related plasticity in prefrontal neurocircuitry. The susceptibility of prefrontal neurocircuitry for tDCS-induced plastic changes and consequent behavioural modulations might depend on the level of learning in a particular task. Variabilities in the cognitive outcome of tDCS might be related to the interaction of tDCS and task-relevant learning. 73 participants completed the Stop Task before and after tDCS over the dorsolateral prefrontal cortex. Participants had to deliver a speeded response upon the onset of a visual go-cue and inhibit the response when the go-cue was replaced by a stop signal. We measured response time (RT) in Go trials, and stop signal reaction time (SSRT) as an index of inhibition ability. A shorter SSRT indicates a better inhibition ability. Participants received either anodal or sham stimulation in two separate sessions (one week apart). RT was increased and SSRT became shorter from pre-stimulation to post-stimulation testing, indicating within-session learning. Furthermore, compared to the first week of testing, RT was increased and SSRT became shorter in the second week, indicating across-session learning. Within-session learning was significantly higher if anodal stimulation was given in the first week rather than the second week indicating that the behavioural effects of tDCS were dependent on the level of learning. Our findings indicate that tDCS effects on executive functions are dependent on the level of experience (learning) in the cognitive task.

The effects of oxytocin on primates' working memory depend on the emotional valence of contextual factors.

Current models suggest that neuropeptide oxytocin modulates the salience of emotional/social stimuli and consequently influences perceptual, attentional and learning processes that underlie social behaviour. Therefore, oxytocin has been considered as a potential treatment in managing social and communication deficits in neuropsychological disorders. Recent studies indicate that effects of oxytocin on social and cognitive functions greatly vary and even lead to opposite outcomes. The factors leading to such variabilities in behavioural effects of oxytocin and their underlying mechanisms remain unclear. Here, we examined the effects of exogenously administered (intranasal) oxytocin (48 IU) on cognitive functions of macaque monkeys within a controlled experimental condition in a randomized crossover study. Monkeys performed a working memory task in which they memorized and subsequently matched stimuli with different emotional/social content (positive, negative, and neutral) at different levels of cognitive difficulties (delay period). Monkeys' accuracy was lower at longer delay intervals indicating that higher cognitive demands adversely affected their performance. There was a significant difference in accuracy and response time between the three emotional conditions. The effects of oxytocin on monkeys' performance were dependent on the emotional content of stimuli so that oxytocin enhanced the adverse effects of negative stimuli, however, moderated the effects of positive stimuli. Our findings in monkeys do not support models suggesting a general effect of oxytocin in enhancing salience or heightening of attention to social stimuli and instead suggest that the cognitive effects of oxytocin depend on the emotional valence of contextual factors.

Context-Dependent Adjustments in Executive Control of Goal-Directed Behaviour: Contribution of Frontal Brain Areas to Conflict-Induced Behavioural Adjustments in Primates.

Psychophysical studies in humans indicate that the performance in various tasks is affected by contextual factors such as conflict level and error commission. It is generally believed that contextual factors influence the executive control processes and consequently modulate ongoing behaviour. Imaging studies suggest that dorsolateral prefrontal cortex and anterior cingulate cortex play crucial roles in mediating these context-dependent adjustments in executive control of behaviour. However, the underlying neuronal processes are to a great extent unknown. Recent studies in non-human primates indicate great similarities in conflict-induced behavioural adjustments between humans and macaque monkeys. Animal models have provided the opportunity to conduct various detailed neurobiological techniques to reveal the neural underpinning of conflict-induced behavioural modulations. In this chapter, we review the latest findings in humans and non-human primate models regarding the neural substrate and underlying mechanisms of conflict-dependent executive control adjustments.

Monitoring Demands for Executive Control: Shared Functions between Human and Nonhuman Primates.

Fifteen years ago, an influential model proposed that the human dorsal anterior cingulate cortex (dACC) detects conflict and induces adaptive control of behavior. Over the years support for this model has been mixed, in particular due to divergent findings in human versus nonhuman primates. We here review recent findings that suggest greater commonalities across species. These include equivalent behavioral consequences of conflict and similar neuronal signals in the dACC, but also a common failure of dACC lesions to reliably abolish conflict-driven behavior. We conclude that conflict might be one among many drivers of adjustments in executive control and that the ACC might be just one component of overlapping distributed systems involved in context-dependent learning and behavioral control.

Direct current stimulation of prefrontal cortex modulates error-induced behavioral adjustments.

Commission of errors and conflict between choices might induce behavioral modulations through adjustments in the executive control of behavior and altered patterns of these modulations are detected in neuropsychiatric disorders. We examined the effects of transcranial Direct Current Stimulation (tDCS) applied over the dorsolateral prefrontal cortex (DLPFC) on error- and conflict-induced behavioral modulations. Two separate cohorts of participants performed two clinically relevant tests of executive control, respectively. In the Wisconsin Card Sorting Test (WCST), the relevant rule for matching items frequently changed and therefore participants had to detect these unannounced changes by trial and error and alter their rule-based behavior. In the Stop task, participants had to rapidly respond to a directional go-signal but inhibit their responses when a stop signal appeared after the go-signal. Each participant received tDCS (sham, cathodal or anodal) in three separate sessions. Errors led to a slower response in the next trial (post-error slowing) in both tasks. The tDCS significantly modulated the post-error slowing in both tasks but did not affect the behavioral adjustments induced by the conflict. The modulation of post-error slowing by tDCS were polarity-dependent and also trial specific appearing immediately after errors. In the WCST and Stop task, the post-error slowing may reflect different processes involved in shifting the behavior-guiding rule and adjustments in inhibitory control of responses, respectively, and we found that the effective tDCS polarity differed between the two tasks. Here, we show that in two separate cognitive tasks direct current stimulation of DLPFC significantly modulated error-induced behavioral modulations.

Sex dependency of inhibitory control functions.

BACKGROUND: Inhibition of irrelevant responses is an important aspect of cognitive control of a goal-directed behavior. Females and males show different levels of susceptibility to neuropsychological disorders such as impulsive behavior and addiction, which might be related to differences in inhibitory brain functions. METHODS: We examined the effects of 'practice to inhibit', as a model of rehabilitation approach, and 'music', as a salient contextual factor in influencing cognition, on the ability of females and males to perform a stop-signal task that required inhibition of initiated or planned responses. In go trials, the participants had to rapidly respond to a directional go cue within a limited time window. In stop trials, which were presented less frequently, a stop signal appeared immediately after the go-direction cue and the participants had to stop their responses. RESULTS: We found a significant difference between females and males in benefiting from practice in the stop-signal task: the percentage of correct responses in the go trials increased, and the ability to inhibit responses significantly improved, after practice in females. While listening to music, females became faster but males became slower in responding to the go trials. Both females and males became slower in performing the go trials following an error in the stop trials; however, music significantly affected this post-error slowing depending on the sex. Listening to music decreased post-error slowing in females but had an opposite effect in males. CONCLUSIONC: Here, we show a significant difference in executive control functions and their modulation by contextual factors between females and males that might have implications for the differences in their propensity for particular neuropsychological disorders and related rehabilitation approaches.

Working Memory in the Service of Executive Control Functions.

Working memory is a type of short-term memory which has a crucial cognitive function that supports ongoing and upcoming behaviors, allowing storage of information across delay periods. The content of this memory may typically include tangible information about features such as the shape, color or texture of an object, and its location and motion relative to the body, as well as phonological information. The neural correlate of working memory has been found in different brain areas that are involved in organizing perceptual or motor functions. In particular, neuronal activity in prefrontal areas encodes task-related information corresponding to working memory across delay periods, and lesions in the prefrontal cortex severely affect the ability to retain this type of memory. Recent studies have further expanded the scope and possible role of working memory by showing that information of a more abstract nature (including a behavior-guiding rule, or the occurrence of a conflict in information processing) can also be maintained in short-term memory, and used for adjusting the allocation of executive control in dynamic environments. It has also been shown that neuronal activity in the prefrontal cortex encodes and maintains information about such abstract entities. These findings suggest that the prefrontal cortex plays crucial roles in the organization of goal-directed behavior by supporting many different mnemonic processes, which maintain a wide range of information required for the executive control of ongoing and upcoming behaviors.

Behavioral consequences of selective damage to frontal pole and posterior cingulate cortices.

Frontal pole cortex (FPC) and posterior cingulate cortex (PCC) have close neuroanatomical connections, and imaging studies have shown coactivation or codeactivation of these brain regions during performance of certain tasks. However, they are among the least well-understood regions of the primate brain. One reason for this is that the consequences of selective bilateral lesions to either structure have not previously been studied in any primate species. We studied the effects of circumscribed bilateral lesions to FPC or PCC on monkeys' ability to perform an analog of Wisconsin Card Sorting Test (WCST) and related tasks. In contrast to lesions in other prefrontal regions, neither posttraining FPC nor PCC lesions impaired animals' abilities to follow the rule switches that frequently occurred within the WCST task. However, FPC lesions were not without effect, because they augmented the ability of animals to adjust cognitive control after experiencing high levels of conflict (whereas PCC lesions did not have any effect). In addition, FPC-lesioned monkeys were more successful than controls or PCC-lesioned animals at remembering the relevant rule across experimentally imposed distractions involving either an intervening secondary task or a surprising delivery of free reward. Although prefrontal cortex posterior to FPC is specialized for mediating efficient goal-directed behavior to maximally exploit reward opportunities from ongoing tasks, our data led us to suggest that FPC is, instead, specialized for disengaging executive control from the current task and redistributing it to novel sources of reward to explore new opportunities/goals.

The essential role of primate orbitofrontal cortex in conflict-induced executive control adjustment.

Conflict in information processing evokes trial-by-trial behavioral modulations. Influential models suggest that adaptive tuning of executive control, mediated by mid-dorsal lateral prefrontal cortex (mdlPFC) and anterior cingulate cortex (ACC), underlies these modulations. However, mdlPFC and ACC are parts of distributed brain networks including orbitofrontal cortex (OFC), posterior cingulate cortex (PCC), and superior-dorsal lateral prefrontal cortex (sdlPFC). Contributions of these latter areas in adaptive tuning of executive control are unknown. We trained monkeys to perform a matching task in which they had to resolve the conflict between two behavior-guiding rules. Here, we report that bilateral lesions in OFC, but not in PCC or sdlPFC, impaired selection between these competing rules. In addition, the behavioral adaptation that is normally induced by experiencing conflict disappeared in OFC-lesioned, but remained normal in PCC-lesioned or sdlPFC-lesioned monkeys. Exploring underlying neuronal processes, we found that the activity of neurons in OFC represented the conflict between behavioral options independent from the other aspects of the task. Responses of OFC neurons to rewards also conveyed information of the conflict level that the monkey had experienced along the course to obtain the reward. Our findings indicate dissociable functions for five closely interconnected cortical areas suggesting that OFC and mdlPFC, but not PCC or sdlPFC or ACC, play indispensable roles in conflict-dependent executive control of on-going behavior. Both mdlPFC and OFC support detection of conflict and its integration with the task goal, but in contrast to mdlPFC, OFC does not retain the necessary information for conflict-induced modulation of future decisions.

Cognitive control functions of anterior cingulate cortex in macaque monkeys performing a Wisconsin Card Sorting Test analog.

Monkeys were trained to select one of three targets by matching in color or matching in shape to a sample. Because the matching rule frequently changed and there were no cues for the currently relevant rule, monkeys had to maintain the relevant rule in working memory to select the correct target. We found that monkeys' error commission was not limited to the period after the rule change and occasionally occurred even after several consecutive correct trials, indicating that the task was cognitively demanding. In trials immediately after such error trials, monkeys' speed of selecting targets was slower. Additionally, in trials following consecutive correct trials, the monkeys' target selections for erroneous responses were slower than those for correct responses. We further found evidence for the involvement of the cortex in the anterior cingulate sulcus (ACCs) in these error-related behavioral modulations. First, ACCs cell activity differed between after-error and after-correct trials. In another group of ACCs cells, the activity differed depending on whether the monkeys were making a correct or erroneous decision in target selection. Second, bilateral ACCs lesions significantly abolished the response slowing both in after-error trials and in error trials. The error likelihood in after-error trials could be inferred by the error feedback in the previous trial, whereas the likelihood of erroneous responses after consecutive correct trials could be monitored only internally. These results suggest that ACCs represent both context-dependent and internally detected error likelihoods and promote modes of response selections in situations that involve these two types of error likelihood.