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.

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.

Sex differences in executive control: A systematic review of functional neuroimaging studies.

The number of studies investigating sex differences in executive functions, particularly those using human functional neuroimaging techniques, has risen dramatically in the past decade. However, the influences of sex on executive function are still underexplored and poorly characterized. To address this, we conducted a systematic literature review of functional neuroimaging studies investigating sex differences in three prominent executive control domains of cognitive set-shifting, performance monitoring, and response inhibition. PubMed, Web of Science, and Scopus were systematically searched. Following the application of exclusion criteria, 21 studies were included, with a total of 677 females and 686 males. Ten of these studies were fMRI and PET, eight were EEG, and three were NIRS. At present, there is evidence for sex differences in the neural networks underlying all tasks of executive control included in this review suggesting males and females engage different strategies depending on task demands. There was one task exception, the 2-Back task, which showed no sex differences. Due to methodological variability and the involvement of multiple neural networks, a simple overarching statement with regard to gender differences during executive control cannot be provided. As such, we discuss limitations within the current literature and methodological considerations that should be employed in future research. Importantly, sex differences in neural mechanisms are present in the majority of tasks assessed, and thus should not be ignored in future research. PROSPERO registration information: CRD42019124772.

A systematic review and meta-analysis of behavioural sex differences in executive control.

Literature investigating whether an individuals' sex affects their executive control abilities and performance on cognitive tasks in a normative population has been contradictory and inconclusive. Using meta-analytic procedures (abiding by PRISMA guidelines), this study attempts to identify the magnitude of behavioural sex differences in three prominent executive control domains of cognitive set-shifting, performance monitoring, and response inhibition. PubMed, Web of Science, and Scopus were systematically searched. Across 46 included studies, a total of 1988 females and 1884 males were included in the analysis. Overall, males and females did not differ on performance in any of the three domains of performance monitoring, response inhibition, or cognitive set-shifting. Task-specific sex differences were observed in the domains of performance monitoring, in the CANTAB Spatial Working Memory task-males scored statistically higher than females (Hedges' g = -0.60), and response inhibition, in the Delay Discounting task-females scored statistically higher than males (Hedges' g = 0.64). While the meta-analysis did not detect overall behavioural sex differences in executive control, significant heterogeneity and task-specific sex differences were found. To further understand sex differences within these specific tasks and domains, future research must better control for age and sex hormone levels.

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 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.

Interactive effects of music and prefrontal cortex stimulation in modulating response inhibition.

Influential hypotheses propose that alterations in emotional state influence decision processes and executive control of behavior. Both music and transcranial direct current stimulation (tDCS) of prefrontal cortex affect emotional state, however interactive effects of music and tDCS on executive functions remain unknown. Learning to inhibit inappropriate responses is an important aspect of executive control which is guided by assessing the decision outcomes such as errors. We found that high-tempo music, but not low-tempo music or low-level noise, significantly influenced learning and implementation of inhibitory control. In addition, a brief period of tDCS over prefrontal cortex specifically interacted with high-tempo music and altered its effects on executive functions. Measuring event-related autonomic and arousal response of participants indicated that exposure to task demands and practice led to a decline in arousal response to the decision outcome and high-tempo music enhanced such practice-related processes. However, tDCS specifically moderated the high-tempo music effect on the arousal response to errors and concomitantly restored learning and improvement in executive functions. Here, we show that tDCS and music interactively influence the learning and implementation of inhibitory control. Our findings indicate that alterations in the arousal-emotional response to the decision outcome might underlie these interactive effects.

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.