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Background/purpose: Cognitive flexibility is a personality trait, which can influence how effectively a healthcare professional can manage a challenging clinical situation. This study explored the cognitive flexibility of undergraduate dental hygiene students at two universities in Asia to gather baseline information in order to consider whether there was an educational need for pre-clinical students with regards to this personality factor. Materials and methods: Participants were all undergraduate dental hygiene students in the 2022 academic year at Tokyo Medical and Dental University (TMDU; n = 79) and Taipei Medical University (TMU; n = 88). An anonymous questionnaire was distributed, which included questions on demographic information and the Cognitive Flexibility Inventory (CFI). Results: The response rates were 97.5% (TMDU) and 89.8% (TMU). The CFI total scores were 91.77 for TMDU and 95.87 for TMU, and there was no significant difference between the two schools. The Alternatives scores were significantly higher in TMU than TMDU (P = 0.044), but there were no significant differences in the Control scores between the two schools. There were also no significant differences between school years of both universities. Conclusion: The dental hygiene students from both dental schools exhibit moderate cognitive flexibility. The educators in both dental schools may consider whether they should investigate and develop this personality factor further during the undergraduate training of their dental hygiene students.

Background and hypothesis: Impaired cognitive flexibility in schizophrenia (SZ) is well documented and correlation with worse functional outcome indicates clinical relevance. Paradigms that assess cognitive flexibility include the Wisconsin Card Sorting Test (WCST) and the Cambridge Neuropsychological Test Automated Battery’s (CANTAB) Intra-Extra Dimensional Set Shift (IED). This systematic review provides an overview of the current state of research on cognitive flexibility in schizophrenia and points out relevant areas of non-consensus. Methods: Two electronic databases (Embase and PubMed) were searched for records published from 1993 to 2024 on adult SZ patients that were assessed for cognitive flexibility/set-shifting ability using WCST and/or IED. Results: 38 studies were included in the review, most of which reported significantly worse performance of SZ patients in WCST and/or IED compared to healthy controls (HC). Most publications focused on the specific profile of cognitive inflexibility. Other aspects included progression of cognitive inflexibility over the course of the illness, neurobiological correlates, IQ as a possible confounder and whether cognitive inflexibility is a heritable trait. Conclusion: Included studies show that cognitive inflexibility rather reflects a stable trait than a state, indicating a lasting prefrontal impairment in SZ. Further longitudinal studies are needed to clarify how these deficits evolve during progression of the disorder. Neither antipsychotic medication nor intelligence seem to explain impaired cognitive flexibility. However, a disease-specific cognitive phenotype has not yet been established and additional research on neuro-computational mechanisms is thus needed to identify possible targets for interventional studies.

Teachers play a crucial role in guiding learners through life's challenges. They face educational and socio-economic shifts while striving to teach for a better future. Our study focuses on equipping future teachers, called pre-service teachers, with resilience-building resources during their teacher training program. A potential antecedent to resilience, which facilitates cognitive strategies and attentional processes, is cognitive flexibility. We first tested whether cognitive flexibility predicts resilience. Next, relying on the tenets of positive psychology, which studies resilience, we developed and tested the effectiveness of character strengths intervention in enhancing pre-service teachers' resilience and cognitive flexibility. An individual's belief in their ability to change personal resources could influence how an intervention manifests. Hence, we studied how mindset impacts the intervention's effect on cognitive flexibility and, thus, resilience. We adopted a multi-method approach, guided by Polk's theory of resilience, to test out objectives.Using a cross-sectional design, study one (n = 273) found that cognitive flexibility significantly predicted resilience. Study two (N = 193; nexp = 133, ncont = 60) was a multi-site field experiment. We found that intervention significantly enhanced resilience (experimental group M = 29.62, control group M = 28.33) and cognitive flexibility (experimental group M = 54.42, control group M = 52.01). Further, a growth mindset, was found to moderate the indirect effect of character strengths intervention on resilience via cognitive flexibility. The study contributes to theoretical and practical advancements in resilience. Taken together, the findings highlight the cognitive-affective-behavioural makeup of resilience and, importantly, the role of cognitive flexibility. The intervention can be seamlessly integrated into teacher training curricula for a resilient future.

Children who experienced moderate perinatal asphyxia (MPA) are at risk of developing long lasting subtle cognitive and behavioral deficits, including learning disabilities and emotional problems. The prefrontal cortex (PFC) regulates cognitive flexibility and emotional behavior. Neurons that release serotonin (5-HT) project to the PFC, and compounds modulating 5-HT activity influence emotion and cognition. Whether 5-HT dysregulations contribute to MPA-induced cognitive problems is unknown. We established a MPA mouse model, which displays recognition and spatial memory impairments and dysfunctional cognitive flexibility. We found that 5-HT expression levels, quantified by immunohistochemistry, and 5-HT release, quantified by in vivo microdialysis in awake mice, are reduced in PFC of adult MPA mice. MPA mice also show impaired body temperature regulation following injection of the 5-HT1A receptor agonist 8-OH-DPAT, suggesting the presence of deficits in 5-HT auto-receptor function on raphe neurons. Finally, chronic treatment of adult MPA mice with fluoxetine, an inhibitor of 5-HT reuptake transporter, or the 5-HT1A receptor agonist tandospirone rescues cognitive flexibility and memory impairments. All together, these data demonstrate that the development of 5-HT system function is vulnerable to moderate perinatal asphyxia. 5-HT hypofunction might in turn contribute to long-term cognitive impairment in adulthood, indicating a potential target for pharmacological therapies.

Dysfunctional activity of the rostral anterior cingulate cortex (rACC) – an extensively connected hub region of the default mode network – has been broadly linked to cognitive and affective impairments in depression. However, the nature of aberrant task-related rACC suppression in depression is incompletely understood. In this study, we sought to characterize functional connectivity of rACC activity suppression (‘deactivation’) – an essential feature of rACC function – during external task engagement in depression. Specifically, we aimed to explore neural patterns of functional decoupling and coupling with the rACC during its task-driven suppression. We enrolled 81 15- to 25-year-old young people with moderate-to-severe major depressive disorder (MDD) before they commenced a 12-week clinical trial that assessed the effectiveness of cognitive behavioral therapy plus either fluoxetine or placebo. Ninety-four matched healthy controls were also recruited. Participants completed a functional magnetic resonance imaging face matching task known to elicit rACC suppression. To identify brain regions associated with the rACC during its task-driven suppression, we employed a seed-based functional connectivity analysis. We found MDD participants, compared to controls, showed significantly reduced ‘decoupling’ of the rACC with extended task-specific regions during task performance. Specifically, less decoupling was observed in the occipital and fusiform gyrus, dorsal ACC, medial prefrontal cortex, cuneus, amygdala, thalamus, and hippocampus. Notably, impaired decoupling was apparent in participants who did not remit to treatment, but not treatment remitters. Further, we found MDD participants showed significant increased coupling with the anterior insula cortex during task engagement. Our findings indicate that aberrant task-related rACC suppression is associated with disruptions in adaptive neural communication and dynamic switching between internal and external cognitive modes that may underpin maladaptive cognitions and biased emotional processing in depression.

For decades, regulatory guidelines for safety assessment in rodents for drugs, chemicals, pesticides, and food additives with developmental neurotoxic potential have recommended a single test of learning and memory (L&M). In recent years some agencies have requested two such tests. Given the importance of higher cognitive function to health, and the fact that different types of L&M are mediated by different brain regions assessing higher functions represents a step forward in providing better evidence-based protection against adverse brain effects. Given the myriad of tests available for assessing L&M in rodents this leads to the question of which tests best fit regulatory guidelines. To address this question, we begin by describing the central role of two types of L&M essential to all mammalian species and the regions/networks that mediate them. We suggest that the tests recommended possess characteristics that make them well suited to the needs in regulatory safety studies. By brain region, these are (1) the hippocampus and entorhinal cortex for spatial navigation, which assesses explicit L&M for reference and episodic memory and (2) the striatum and related structures for egocentric navigation, which assesses implicit or procedural memory and path integration. Of the tests available, we suggest that in this context, the evidence supports the use of water mazes, specifically, the Morris water maze (MWM) for spatial L&M and the Cincinnati water maze (CWM) for egocentric/procedural L&M. We review the evidentiary basis for these tests, describe their use, and explain procedures that optimize their sensitivity.

Iron is an important cofactor for many proteins and is used to create Fe-S clusters and heme prosthetic groups that enzymes use to catalyze enzymatic reactions. Proteins involved in the import, export, and sequestration of iron are regulated by Iron Regulatory Proteins (IRPs). Recently, a patient with bi-allelic loss of function mutations in IREB2 leading to the absence of IRP2 protein was discovered. The patient failed to achieve developmental milestones and was diagnosed with dystonic cerebral palsy, epilepsy, microcytic hypochromic anemia, and frontal lobe atrophy. Several more IREB2 deficient patients subsequently identified manifested similar neurological problems. To better understand the manifestations of this novel neurological disease, we subjected an Irp2-null mouse model to extensive behavioral testing. Irp2-null mice had a significant motor deficit demonstrated by reduced performance on rotarod and hanging wire tests. Somatosensory function was also compromised in hot and cold plate assays. Their spatial search strategy was impaired in the Barnes maze and they exhibited a difficulty in flexibly adapting their response in the operant touchscreen reversal learning task. The latter is a cognitive behavior known to require an intact prefrontal cortex. These results suggest that loss of Irp2 in mice causes motor and behavioral deficits that faithfully reflect the IREB2 patient's neurodegenerative disorder.

The aim was to examine the effects of modalities of acute resistance exercise (RE) on cognition and hemodynamics including internal carotid artery (ICA) blood flow (BF). Twenty adults completed familiarization and experimental visits. One-repetition maximum (1RM) for bilateral leg extension was quantified, and baseline executive functioning was determined from three run-in visits. Subsequent visits included three randomized, volume-equated, acute exercise bouts of 30 %1RM+blood flow restriction (BFR), 30 %1RM, and 70 %1RM. Both 30 %1RM trials completed four sets of exercise (1 × 30, 3 × 15), and the 70 %1RM condition completed four sets of 8 repetitions. BFR was induced with 40 % of the pressure to occlude the femoral arteries. 11 min following each exercise, participants completed the Stroop and Shifting Attention Tests. Baseline and post-exercise values were used to calculate change scores. The resulting mean change scores were evaluated with mixed factorial ANOVAs. A p≤0.05 was considered significant. All measured outcome variables increased in response to exercise. The ANOVAs for cognitive scores indicated no significant (p>0.05) interactions. For cognitive flexibility and executive function index, there were main effects of Sex. Change scores of the females were significantly greater than the males for cognitive flexibility (7.6 ± 5.9 vs. -2.6 ± 8.4 au; p=0.007) and executive function index (7.4 ± 4.6 vs. -2.5 ± 6.5 au; p=0.001). For ICA BF, there was no significant interaction or any main effect. The females exhibited a smaller exercise-induced increase in blood pressure compared to the males (17.7 ± 5.9 vs. 11.0 ± 4.1 mmHg; p=0.010). Each RE modality yielded acute improvements in cognition, but only for females. There were no cognitive improvements related to BFR such that each RE bout yielded similar results.

Predicting the risk for general psychopathology (the p factor) requires the examination of multiple factors ranging from brain to cognitive skills. While an increasing number of findings have reported the roles of the cerebral cortex and executive functions, it is much less clear whether and how the cerebellum and cognitive flexibility (a core component of executive function) may be associated with the risk for general psychopathology. Based on the data from more than 400 children aged 6–12 in the Children School Functions and Brain Development (CBD) Project, this study examined whether the left cerebellar lobule VIIb and its connectivity within the cerebellum may prospectively predict the risk for general psychopathology one year later and whether cognitive flexibility may mediate such predictions in school-age children. The reduced gray matter volume in the left cerebellar lobule VIIb and the increased connectivity of this region to the left cerebellar lobule VI prospectively predicted the risk for general psychopathology and was partially mediated by worse cognitive flexibility. Deficits in cognitive flexibility may play an important role in linking cerebellar structure and function to the risk for general psychopathology.

The production of behavioural flexibility requires the coordination and integration of information from across the brain, by the dorsal striatum. In particular, the striatal cholinergic system is thought to be important for the modulation of striatal activity. Research from animal literature has shown that chemical inactivation of the dorsal striatum leads to impairments in reversal learning. Furthermore, proton magnetic resonance spectroscopy work has shown that the striatal cholinergic system is also important for reversal learning in humans. Here, we aim to assess whether the state of the dorsal striatal cholinergic system at rest is related to serial reversal learning in humans. We provide preliminary results showing that variability in choline in the dorsal striatum is significantly related to both the number of perseverative and regressive errors that participants make, and their rate of learning from positive and negative prediction errors. These findings, in line with previous work, suggest the resting state of dorsal striatal cholinergic system has important implications for producing flexible behaviour. However, these results also suggest the system may have heterogeneous functionality across different types of tasks measuring behavioural flexibility. These findings provide a starting point for further interrogation into understanding the functional role of the striatal cholinergic system in flexibility.

Hormone therapy (HT) has failed to improve learning and memory in postmenopausal women according to recent clinical studies; however, the reason for failure of HT in improving cognitive performance is unknown. In our research, we found cognitive flexibility was improved by 17β-Estradiol (E2) in mice 1 week after ovariectomy (OVXST), but not in mice 3 months after ovariectomy (OVXLT). Isobaric tags for relative and absolute quantitation (iTRAQ) revealed increased cannabinoid receptor interacting protein 1 (CNRIP1) in E2-treated OVXLT mice compared with E2-treated OVXST mice. Adeno-associated virus 2/9 (AAV2/9) delivery of Cnrip1 short-hairpin small interfering RNA (Cnrip1-shRNA) rescued the impaired cognitive flexibility in E2 treated OVXLT mice. This effect is dependent on CB1 function, which could be blocked by AM251—a CB1 antagonist. Our results indicated a new method to increasing cognitive flexibility in women receiving HT by disrupting CNRIP1.

As integral to the EFL learners' achievement and intellectual development, good language teachers need to be familiar with the influential factors hindering or promoting their success. Positive psychology paying attention to positive traits highlights the factors that boost performance. In this line, by taking boosters of being a successful teacher, the aim of the current study is to consider the interplay between Chinese EFL instructors' professional success, workplace buoyancy, and cognitive flexibility. Then, it is considered whether EFL teachers' buoyancy and cognitive flexibility can predict success. Accordingly, 328 Chinese EFL teachers were conveniently selected to participate in this study. To analyze the collected data, multiple regression analysis and Spearman Rho correlation index as well as ANOVA were employed. The findings are an indication of a direct and significant correlation and coaction among EFL teachers’ cognitive flexibility, workplace buoyancy, and professional success. Additionally, the results indicate that the cognitive flexibility of EFL teachers can be one of the significant predictors of success in their profession. Our findings imply that teachers need to enhance their positive personality traits such as cognitive flexibility and buoyancy to be successful in their profession.

Revealing the pupillary correlates of depression-prone individuals is conducive to the early intervention and treatment of depression. This study recruited 31 depression-prone and 31 healthy individuals. They completed an emotional task-switching task combined with a go/no-go task, and task-evoked pupillary responses (TEPR) were recorded. Behavioral results showed no significant differences in behavioral performance in terms of cognitive flexibility and inhibition between the depression-prone group and the healthy control group. The pupillary results revealed that (1) the depression-prone group showed slightly lower TEPRs to positive stimuli than the healthy controls during cue presentation; (2) during target presentation, the depression-prone group did not show an effect of emotional valence on the pupillary response in the task-repeat trials; and (3) compared to the healthy controls, the depression-prone group showed significantly smaller TEPRs to negative no-go stimuli and had a longer latency of the second peak of pupil dilation in no-go trials. These results imply that depression-prone individuals may have slower neural responses in cognitive control tasks and emotion-specific weakened cognitive control than healthy individuals., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Post-traumatic stress disorder (PTSD) is associated with deficits in cognitive flexibility, with evidence suggesting that these deficits may be a risk factor for the development of core PTSD symptoms. Understanding the neurophysiological substrate of this association could aid the development of effective therapies for PTSD. In this study, we investigated the relationship between post-traumatic stress severity (PTSS) in service members with combat exposure and the modulation of cortical oscillatory activity during a test of cognitive flexibility. Participants were assigned to three groups based on PTSS scores: low (well below a threshold consistent with a diagnosis of PTSD, n = 30), moderate (n = 32), and high (n = 29) symptom severity. Magnetoencephalography data were recorded while participants performed a cued rule-switching task in which two matching rules were repeated or switched across consecutive trials. Participants with high PTSS had longer reaction times for both switch and repeat trials, and showed evidence of sustained residual interference during repeat trials. During the cue-stimulus interval, participants with moderate and high PTSS showed higher relative theta power in switch trials over left dorsolateral prefrontal cortex (DLPFC). After test-stimulus onset, participants with high PTSS showed less suppression of beta band activity, which was present over multiple prefrontal, parietal, and temporal regions in switch trials, but it was confined to ventromedial prefrontal cortex in repeat trials. Higher theta band activity is a marker of effortful voluntary shifting of attention, while lower suppression of beta band activity reflects difficulties with inhibition of competing perceptual information and courses of action. These findings are consistent with a role for altered suppression of beta band activity, which can be due to less effective top-down bias signals exerted by DLPFC, in the etiology of cognitive flexibility deficits in PTSD.

The aim of this paper is to investigate the ethical and responsible use of AI chatbots in education in support of critical thinking, cognitive flexibility and self-regulation in terms of their potential to enhance and motivate teaching and learning in contemporary education environments. AI chatbots such as ChatGPT by OpenAI appear to be improving in conversational and other capabilities and this paper explores such advances using version 4. Based on a review of the research literature, a conceptual framework is formulated for responsible use of AI chatbots in education supporting cognitive flexibility in AI-rich learning environments. The framework is then operationalized for use in this paper through the development of exemplars for math, english language arts (ELA), and studying with ChatGPT to close learning gaps in an effort to foster more ethical and responsible approaches to the design and development of AI chatbots for application and use in teaching and learning environments. This paper extends earlier foundational work on cognitive flexibility and AI chatbots as well as work on cognitive flexibility in support of creativity and innovation with AI chatbots in urban civic spaces.

Background: Cognitive flexibility is a frontal lobe function, and some scholars have indicated that it is linked to depression. The Cognitive Flexibility Test (CFT) is a neuropsychological test that can easily and promptly measure cognitive flexibility within a short amount of time. This study focuses on healthy younger workers to determine the associations between their cognitive flexibility, depression, and performance at work. Methods: The absolute absenteeism and the absolute presenteeism of a group of 80 regular employees were measured, and the employees were administered the Verbal Fluency Test (VTF), the CFT-A and CFT-B, the Beck Depression Inventory-II (BDI-2), and the World Health Organization Health and Work Performance Questionnaire (WHO-HPQ). Google Forms were used to measure the BDI-2, absolute absenteeism, and absolute presenteeism, and online interviews were conducted on Zoom to collect answers to the CFT and the Verbal Fluency Test (VFT). Results: No significant age-related differences appeared in the number of responses obtained for the CFT-A and CFT-B from subjects grouped according to the decades they represented, ranging from the 20s to the 50s. In addition, the CFT-A and CFT-B did not indicate significant correlations between the BDI-2 and absenteeism and presenteeism. Limitations: Small sample, online vs. in person assessments due to COVID-19. Conclusion: The results suggest that the function of cognitive flexibility is relatively stable and is unaffected by age brackets. The study also found no links between the cognitive flexibility of healthy young workers, the state of depression, or their work performance.

The present study examined cognitive flexibility as a mediator in the relationship between bilingualism and creativity. Other variables, such as cultural orientation, multicultural experience, and second language acquisition age, were also included to comprehensively understand associations with creativity. The mediation effect of cognitive flexibility was analyzed using a bootstrapping method with a sample of 89 Korean-English bilingual college students through an online survey. Findings indicated that bilingualism was not statistically associated with creativity but that cognitive flexibility mediated the relationship between bilingualism and creative ideation (i.e., fluency, originality, and flexibility), indicating that the relationship of creative ideation with bilingualism depended on cognitive flexibility. Also, cognitive flexibility played an important role in the relationship between multicultural experience and two indices of creative potential (i.e., fluency and flexibility, but not originality). Bilingualism was the most accurate predictor of cognitive flexibility. Limitations and future research are discussed.

Cognitive theory of boredom presumes that boredom, an important potential indicator for self-dysregulation, represents to be the result of attention failure. And lapses of attention have been shown to act as a key signal in mind wandering (especially spontaneous mind wandering), which has been found to be positively associated with boredom. If both mind wandering and boredom concurrently occupy individuals' on-task processing resources, it would definitely influence their cognitive flexibility, which is an essential component for self-regulation. Until now, however, there has been little discussion about mind wandering, boredom, and cognitive flexibility at the same time. The present study investigated the hypothesis that boredom can mediate the effect of mind wandering on cognitive flexibility at trait-level by adopting a cross-sectional exploratory study design and anonymous structured questionnaires in three studies (N = 449,182 and 190 for Studies 1, 2 and 3, respectively). Correlation analysis demonstrated that mind wandering (especially spontaneous mind wandering) was positively related to boredom, and that cognitive flexibility was negatively related to mind wandering and boredom, respectively. Mediation analysis revealed an indirect effect of mind wandering (especially spontaneous mind wandering) on cognitive flexibility through boredom. In conclusion, these findings are useful to build a theoretical framework for future clinical practice. An implication of these findings is the possibility that efficacious strategies targeting at reducing boredom are needed to decrease the detriment effect of spontaneous mind wandering on cognitive flexibility.

Sleep deprivation (SD) causes significant deficits in multiple aspects of cognition, including sustained attention and working memory. Investigating the neural processes underpinning these cognitive losses has proven challenging due to the confounds of current animal tasks; many employ appetitive or aversive stimuli to motivate behavior, while others lack task complexity that translates to human studies of executive function. We established the Lux Actuating Search Task (LAST) to circumvent these issues. The LAST is performed in a circular, open-field arena that requires rats to find an unmarked, quasi-randomly positioned target. Constant low-level floor vibrations motivate ambulation, while light intensity (determined by the rodent's proximity to the target destination) provides continuous visual feedback. The task has two paradigms that differ based on the relationship between the light intensity and target proximity: the Low Lux Target (LLT) paradigm and the High Lux Target paradigm (HLT). In this study, on days 1–6, the rats completed nine trials per day on one of the two paradigms. On day 7, the rats were either sleep deprived by gentle handling or were left undisturbed before undertaking the opposite (reversal) paradigm on days 7–9. Our results showed that SD significantly impeded the ability of Long Evans rats to learn the reversal paradigm, as indicated by increased times to target and increased failure percentages compared to rats whose sleep was undisturbed. Rats also showed reduced learning with the HLT paradigm, as the initial task or as the reversal task, likely due to the rodents' photophobia limiting their motivation to navigate toward a bright light, which is required to succeed.

Remembering the location of food is essential for survival. Rodents and humans employ mainly hippocampus-dependent spatial strategies, but when being stressed they shift to striatum-mediated stimulus-based strategies. To investigate underlying brain circuits, we tested mice with a heightened stress susceptibility due to a lack of the GABA-synthetizing enzyme GAD65 (GAD65−/− mice) in a dual solution task. Here, GAD65−/− mice preferred to locate a food reward in an open field via a proximal cue, while their wildtype littermates preferred a spatial strategy. The analysis of cFos co-activation across brain regions and of stress-induced mRNA expression changes of GAD65 pointed towards the hippocampal dorsal dentate gyrus (dDG) as a central structure for mediating stress effects on strategy choices via GAD65. Reducing the GAD65 expression locally in the dDG by a shRNA mediated knock down was sufficient to replicate the phenotype of the global GAD65 knock out and to increase dDG excitability. Using DREADD vectors to specifically interfere with dDG circuit activity during dual solution retrieval but not learning confirmed that the dDG modulates strategy choices and that a balanced excitability of this structure is necessary to establish spatial strategy preference. These data highlight the dDG as a critical hub for choosing between spatial and non-spatial foraging strategies.

The current study aimed to validate the Russian version of the Child Behaviour Motivation Scale (CBeMO), examine gender differences in motivational tendencies, and explore the impact of executive functions on learning motivation tendencies among children. The sample consisted of 434 typically developing 5–6 years old children. The confirmatory factor analysis showed that according to the evaluation criteria, the model is poorly fitted to the data. However, internal consistency analysis confirmed acceptable levels of reliability and unidimensionality of the CBeMO scales. The identified internal structure of CBeMO indicates an overlap between CBeMO items related to task avoidance and social dependence on the Russian sample. The study revealed differences between girls and boys in all three CBeMO scales. Concerning executive functioning, it was revealed that motor persistence skills and working memory have an impact on the learning motivation tendencies among children, when controlling for group size, age, gender and non-verbal intelligence.

Adverse early life experiences, such as maternal separation, are associated with an increased risk for several mental health problems. Symptoms induced by maternal separation that mirror clinically relevant aspects of mental problems, such as cognitive inflexibility, open the possibility of testing putative therapeutics prior to clinical development. Although several animal (e.g., rodent) studies have evaluated the effects of early maternal separation on cognitive flexibility, no consistent conclusions have been drawn. To clarify this issue, in this study, a meta-analysis method was used to systematically explore the relationship between early maternal separation and cognitive flexibility in rodent offspring. Results indicate that early maternal separation could significantly impair cognitive flexibility in rodent offspring. Moderator analyses further showed that the relationship between early maternal separation and cognitive flexibility was not consistent in any case, but was moderated by variations in the experimental procedures, such as the deprivation levels, task characteristics, and rodent strains. These clarify the inconsistent effects of maternal separation on cognitive flexibility in rodents and help us better understand the association between early life adversity and cognitive development.

ABSTRACT: From the perspective of cognitive mechanisms, this research discusses the effects of cognitive flexibility, entrepreneurial self-efficacy, and optimism on entrepreneurship competence. Qualitative interviews have revealed the general relationship between key concepts. SEM analysis further shows that cognitive flexibility has a positive direct effect on entrepreneurial self-efficacy; entrepreneurial self-efficacy has a positive direct effect on entrepreneurship competence; cognitive flexibility has a positive direct effect on entrepreneurship competence; cognitive flexibility has a positive indirect effect on entrepreneurship competence through entrepreneurial self-efficacy; optimism moderates the relationship between cognitive flexibility and entrepreneurship competence, with an inverted U-shaped moderation effect. According to the results, this research offers some suggestions to improve entrepreneurs’ entrepreneurship competence from the perspective of cognition and positive psychology, hoping that through the overall improvement of entrepreneurs’ entrepreneurship competence, it can be beneficial to the open innovation atmosphere of the whole society.

Our actions cause manifold environmental changes. Monitoring these action effects serves at least two vital functions: While the validation of currently relevant effects assesses goal-achievement, screening for currently irrelevant effects accumulates knowledge about potential action-effect relationships. However, monitoring the perceptual consequences of our actions presumably impairs performance in concurrent tasks. Here, we investigated how effect relevance modulates monitoring costs by manipulating instructions in three dual-task experiments. We found performance decreases not only after validation of goal-relevant action effects but to a smaller extent also after screening of goal-irrelevant action effects. These results suggest that effect monitoring is a rather fundamental limitation of dual tasking.

Background: A top-down neuronal circuit from the orbitofrontal cortex (OFC) to the dorsomedial striatum (DMS) appears to be critical for cognitive flexibility. However, how OFC projections to different types of neurons in the DMS control cognitive flexibility and contribute to substance seeking and use, which are relatively inflexible behaviors, remains unclear., Methods: Mice were trained on 2-bottle choice and operant alcohol self-administration procedures. The cognitive flexibility of the mice was tested through a place discrimination task. Electrophysiology and in vivo optogenetics were used to test the function of neural circuits in alcohol-seeking behavior., Results: We depicted a connection from the OFC to striatal neurons and found that OFC afferents could elicit functional flexibility in striatal cholinergic interneurons (CINs). A mouse model of chronic alcohol consumption showed impaired cognitive flexibility and reduced burst-pause firing. The impairment of the OFC-DMS circuit resulted in a reduction in glutamatergic transmission in OFC medium spiny neurons (MSNs) through a CIN-mediated preinhibition mechanism. Importantly, remodeling the OFC-DMS circuit by inducing long-term potentiation restored cognitive flexibility. Furthermore, CINs were responsible for the impact of remodeling of the OFC-DMS circuit on cognitive flexibility. This regulatory role of CINs preferentially facilitated the potentiation of glutamatergic transmission in D 2 receptor-expressing MSNs, but not in D 1 receptor-expressing MSNs. Finally, activation of the OFC-CIN-D 2 receptor-expressing MSN circuit decreased alcohol-seeking behavior., Conclusions: Improving OFC-CIN circuit-mediated cognitive flexibility may provide a novel strategy for treating uncontrolled alcohol-seeking behavior., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Stress reduces cognitive flexibility and dopamine D1 receptor-related activity in the prelimbic cortex (PL), effects hypothesized to depend on reduced corticotropic releasing factor receptor type 1 (CRFr1) regulation of dopamine neurons in the ventral tegmental area (VTA). We assessed this hypothesis in rats by examining the effect of chronic unpredictable restraint stress (CUS), mild acute stress, or their combination on cognitive flexibility, CRFr1 expression in the VTA and D1-related activity in PL. In Experiment 1, rats received either CUS or equivalent handling for 14 days before being trained to press two levers to earn distinct food outcomes. Initial learning was assessed using an outcome devaluation test after which cognitive flexibility was assessed by reversing the outcomes earned by the actions. Prior to each reversal training session, half the CUS and controls receiving acute stress with action-outcome updating assessed using a second devaluation test and CRFr1 expression in the VTA assessed using in-situ hybridisation. Although CUS did not itself affect action-outcome learning, its combination with acute stress blocked reversal learning and decreased VTA CRFr1 expression after acute shock. The relationship between these latter two effects was assessed in Experiment 2 by pharmacologically disconnecting the VTA and PL, unilaterally blocking neurons expressing CRFr1 in the VTA and D1 receptors in the contralateral PL during reversal learning after acute stress. Acute stress again blocked reversal learning but only in the group with VTA-PL disconnection, demonstrating that VTA CRFr1-induced facilitation of dopaminergic activity in the PL is necessary for maintaining cognitive flexibility after acute stress. [250].

The mammalian dorsomedial prefrontal cortex (dmPFC) receives diverse inputs and plays important roles in adaptive behavior and cognitive flexibility. Stress, a major risk factor for many psychiatric disorders, compromises the structure and function of multiple brain regions and circuits. Here we show that 7-day restraint stress impairs reversal learning in the 4-choice odor discrimination test, a decision-making task requiring an intact dmPFC. In vivo two-photon imaging further reveals that stress increases dmPFC dendritic spine elimination, particularly those of the mushroom morphology, without affecting spine formation. In addition, stress alters dmPFC microglial branching complexity and elevates their terminal process dynamics. In stressed mice, dmPFC microglia contact dendrites more frequently, and dendritic spines with microglial contact are prone to elimination. In summary, our work suggests that stress-induced changes in glial-synapse interaction contributes to synaptic loss in dmPFC, resulting in neuronal circuit deficits and impaired cognitive flexibility.

Adolescence is a developmental period that dramatically impacts body and behavior, with pubertal hormones playing an important role not only in the morphological changes in the body but also in brain structure and function. Understanding brain development during adolescence has become a priority in neuroscience because it coincides with the onset of many psychiatric and behavioral disorders. However, little is known about how puberty influences the brain functional connectome. In this study, taking a longitudinal human sample of typically developing children and adolescents (of both sexes), we demonstrate that the development of the brain functional connectome better fits pubertal status than chronological age. In particular, centrality, segregation, efficiency, and integration of the brain functional connectome increase after the onset of the pubertal markers. We found that these effects are stronger in attention and task control networks. Lastly, after controlling for this effect, we showed that functional connectivity between these networks is related to better performance in cognitive flexibility. This study points out the importance of considering longitudinal nonlinear trends when exploring developmental trajectories, and emphasizes the impact of puberty on the functional organization of the brain in adolescence.

Background: Research has found that IU (Intolerance of Uncertainty) and CF (Cognitive Flexibility) have separately been associated with depression, anxiety and eating disorders as a transdiagnostic vulnerability. This study evaluated the mediational effect of both IU and CF on the relationship between neuroticism and depressive, anxiety and eating disorder symptoms. We hypothesised that IU and CF when examined together would both significantly mediate the relationship between neuroticism and depression, generalised anxiety, panic disorder, social phobia, PTSD and eating disorder symptoms. Methods: Data was collected through advertising the study at a university campus, Amazon Mechanical Turk and a university psychology clinic. Participants included a total of 717 individuals for which data was available. Mediation analyses were conducted using the PROCESS macro in SPSS. Results: IU and CF were found to significantly mediate the relationship between neuroticism and symptom measures of depression, generalised anxiety, panic disorder, social phobia and PTSD. IU, but not CF, significantly mediated the relationship between neuroticism and eating disorder symptoms. All analyses controlled for gender. Limitations: The study's limitations include the cross-sectional design precluding causality and that participants provided self-report data. Conclusions: IU and CF are transdiagnostic mediators in the relationship between neuroticism and depression and anxiety. IU was also found to be a significant mediator for eating disorder symptoms but CF was not. Findings suggest the importance of focusing on the these factors during assessment and treatment across emotional and eating disorders.

Stressful events are thought to impair the flexible adaptation to changing environments, yet the underlying mechanisms are largely unknown. Here, we combined computational modeling and functional magnetic resonance imaging (fMRI) to elucidate the neurocomputational mechanisms underlying stress-induced deficits in flexible learning. Healthy participants underwent a stress or control manipulation before they completed, in the MRI scanner, a Markov decision task, frequently used to dissociate model-based and model-free contributions to choice, with repeated reversals of reward contingencies. Our results showed that stress attenuated the behavioral sensitivity to reversals in reward contingencies. Computational modeling further indicated that stress specifically affected the use of value computations for subsequent action selection. This reduced application of learned information on subsequent behavior was paralleled by a stress-induced reduction in inferolateral prefrontal cortex activity during model-free computations. For model-based learning, stress decreased specifically posterior, but not anterior, hippocampal activity, pointing to a functional segregation of model-based processing and its modulation by stress along the hippocampal longitudinal axis. Our findings shed light on the mechanisms underlying deficits in flexible learning under stress and indicate that, in highly dynamic environments, stress may hamper both model-based and model-free contributions to adaptive behavior.

Task-switching cost is highly reliable in old participants. However, in a Stroop-switching paradigm that compared old musicians with old non-musicians (Experiment 1A), task-switching costs were not consistent. For non-musicians, the task-switching costs were significant in the congruent and neutral trials, but not in the incongruent trials. For musicians, the task-switching costs disappeared completely. We suspected that besides following task rules, old participants might also apply a stimulus-based strategy called the target-first strategy. In Experiment 1B and 2, participants in Experiment 1A were invited again to perform two more Stroop-switching paradigms. To encourage the participants to use task rules, in Experiment 1B we removed the neutral trials but found the same results as in Experiment 1A. In Experiment 2, when inserting a cue-target interval in the Stroop-switching paradigm, both musicians and non-musicians produced reliable task-switching costs in all trial conditions. Note that younger participants had reliable task-switching costs in Experiment 1B and 2. We suggest that older participants preferred the target-first strategy to the task rules-based strategy because the former was easy to implant although it was less flexible. Besides task-switching costs, we found that old musicians had less interference effect than old non-musicians in Experiment 1B. In all three experiments, old musicians had shorter RTs than old non-musicians, which might be due to differences in strategies apart from cognitive abilities. We propose that without considering the strategy preference, some previous studies might misestimate the difference between old and young participants in terms of task-switching performance and interference control.

We need to be able to learn new behaviour, but also be capable of changing existing routines, when they start conflicting with our long-term goals. Little is known about to what extent blank-slate learning of new and adjustment of existing behavioural routines rely on different neural and bodily mechanisms. In the current study, participants first acquired novel stimulus–response contingencies, which were subsequently randomly changed to create the need for flexible adjustments. We measured midfrontal theta oscillations via EEG as an indicator of neural conflict processing, as well as heart rate as a proxy of autonomic activity. Participants’ trial-wise learning progress was estimated via computation modelling. Theta power and heart rate significantly differed between correct and incorrect trials. Differences between correct and incorrect trials in both neural and cardiac feedback processing were more pronounced for adjustments compared to blank-slate learning. This indicates that both midfrontal and cardiac processing are sensitive to changes in stimulus–response contingencies. Increases in individual learning rates predicted lower impact of performance feedback on midfrontal theta power, but higher impact on heart rate. This suggests that cardiac and midfrontal reactivity are partially reflective of different mechanisms related to feedback learning. Our results shed new light on the role of neural and autonomic mechanisms for learning and behavioural adjustments.

A key element of human flexible behavior concerns the ability to continuously predict and prepare for sudden changes in tasks or actions. Here, we tested whether people can dynamically modulate task preparation processes and decision-making strategies when the identity of a to-be-performed task becomes uncertain. To this end, we developed a new paradigm where participants need to prepare for one of nine tasks on each trial. Crucially, in some blocks, the task being prepared could suddenly shift to a different task after a longer cue-target interval, by changing either the stimulus category or categorization rule that defined the initial task. We found that participants were able to dynamically modulate task preparation in the face of this task uncertainty. A second experiment shows that these changes in behavior were not simply a function of decreasing task expectancy, but rather of increasing switch expectancy. Finally, in the third and fourth experiment, we demonstrate that these dynamic modulations can be applied in a compositional manner, depending on whether either only the stimulus category or categorization rule would be expected to change., (Copyright © 2023. Published by Elsevier B.V.)

Previous research on media multitasking has often focussed on the frequency with which people perform this type of behaviour. Heavy media multitaskers have been found to differ from light media multitaskers in their performance of tasks involving executive functioning (although these differences have not always been found consistently). The aim of the present study was to explore individuals’ executive functioning in relation to their ability to media multitask (i.e., their ability to retain information presented during the session), rather than their propensity to media multitask. Participants (N ​= ​116, aged 18–25, male N ​= ​32) completed an executive function task battery, inclusive of working memory, inhibition and cognitive flexibility tasks, followed by a studious media multitasking situation. Individual executive function task performance scores were correlated with media multitasking ability scores. Greater cognitive flexibility was significantly associated with greater ability to media multitask, in terms of retention of information from a media multitasking situation. Furthermore, media multitasking influenced mood, reducing levels of self-reported arousal. Thus, the present study provides some elucidation as to what cognitive characteristics are involved in being able to media multitask, whilst also indicating a possible cognitive mechanism for negative associations found between media multitasking and academic performance.

Increasing attention is being directed towards explicating the neurocognitive mechanisms of divergent thinking. While neuroimaging studies have tended to dominate the contemporary creativity literature, lesion studies provide important converging evidence by revealing the regions that are not only implicated in, but essential for, task performance. Here we explored the capacity for divergent thinking in semantic dementia (SD), a neurodegenerative disorder characterised by the progressive degeneration of the conceptual knowledge base. The performance of 10 SD patients on a divergent thinking task was contrasted with that of 15 patients with the behavioural variant of frontotemporal dementia (bvFTD) and 20 healthy control participants. In addition, all participants underwent neuropsychological testing and structural MRI. Relative to controls, both patient groups generated significantly fewer responses on the divergent thinking task, with disproportionate impairment in the SD group. Further, the responses generated by patient groups were less original and reflected less flexible thinking when compared with controls. For SD patients, fluency of responses correlated with performance on a measure of semantic association, and originality of responses correlated with semantic naming and comprehension ability. In bvFTD, originality of ideas correlated with letter fluency and response inhibition. Voxel-based morphometry analyses revealed two grey matter clusters consistently associated with diminished Fluency of ideas, namely a left medial temporal lobe cluster centred on the left anterior hippocampus, and a left middle frontal gyrus cluster. Our study highlights the importance of distinct temporal and prefrontal contributions to divergent thinking via a lesion approach, and underscores the pivotal role of semantic processes in creative cognition.

Mutations and copy number variants affecting DYRK1A gene encoding the dual-specificity tyrosine phosphorylation-regulated kinase 1A are among the most frequent genetic causes of neurodevelopmental disorders including autism spectrum disorder (ASD) associated with microcephaly, febrile seizures and severe speech acquisition delay. Here we developed a mouse model harboring a frame-shift mutation in Dyrk1a resulting in a protein truncation and elimination of its kinase activity site. Dyrk1a+/− mice showed significant impairments in cognition and cognitive flexibility, communicative ultrasonic vocalizations, and social contacts. Susceptibility to hyperthermia-induced seizures was also significantly increased in these mice. The truncation leading to haploinsufficiency of DYRK1A in mice thus recapitulates the syndromic phenotypes observed in human patients and constitutes a useful model for further investigations of the mechanisms leading to ASD, speech delay and febrile seizures.

Objective: Brain dynamics underlie flexible cognition and behavior, yet little is known regarding this relationship in autism spectrum disorder (ASD). We examined time-varying changes in functional co-activation patterns (CAPs) across rest and task-evoked brain states to characterize differences between children with ASD and typically developing (TD) children and identify relationships with severity of social behaviors and restricted and repetitive behaviors. Method: 17 children with ASD and 27 TD children ages 7–12 completed a resting-state fMRI scan and four runs of a non-cued attention switching task. Metrics indexing brain dynamics were generated from dynamic CAPs computed across three major large-scale brain networks: midcingulo-insular (M-CIN), medial frontoparietal (M-FPN), and lateral frontoparietal (L-FPN). Results: Five time-varying CAPs representing dynamic co-activations among network nodes were identified across rest and task fMRI datasets. Significant Diagnosis × Condition interactions were observed for the dwell time of CAP 3, representing co-activation between nodes of the M-CIN and L-FPN, and the frequency of CAP 1, representing co-activation between nodes of the L-FPN. A significant brain-behavior association between dwell time of CAP 5, representing co-activation between nodes of the M-FPN, and social abilities was also observed across both groups of children. Conclusion: Analysis of brain co-activation patterns reveals altered dynamics among three core networks in children with ASD, particularly evident during later stages of an attention task. Dimensional analyses demonstrating relationships between M-FPN dwell time and social abilities suggest that metrics of brain dynamics may index individual differences in social cognition and behavior.

Humans and some other animals can autonomously generate action choices that contribute to solving complex problems. However, experimental investigations of the cognitive bases of human autonomy are challenging, because experimental paradigms typically constrain behaviour using controlled contexts, and elicit behaviour by external triggers. In contrast, autonomy and freedom imply unconstrained behaviour initiated by endogenous triggers. Here we propose a new theoretical construct of adaptive autonomy, meaning the capacity to make behavioural choices that are free from constraints of both immediate external triggers and of routine response patterns, but nevertheless show appropriate coordination with the environment. Participants (N = 152) played a competitive game in which they had to choose the right time to act, in the face of an opponent who punished (in separate blocks) either choice biases (such as always responding early), sequential patterns of action timing across trials (such as early, late, early, late…), or predictable action-outcome dependence (such as win-stay, lose-shift). Adaptive autonomy was quantified as the ability to maintain performance when each of these influences on action selection was punished. We found that participants could become free from habitual choices regarding when to act and could also become free from sequential action patterns. However, they were not able to free themselves from influences of action-outcome dependence, even when these resulted in poor performance. These results point to a new concept of autonomous behaviour as flexible adaptation of voluntary action choices in a way that avoids stereotypy. In a sequential analysis, we also demonstrated that participants increased their reliance on belief learning in which they attempt to understand the competitor's beliefs and intentions, when transition bias and reinforcement bias were punished. Taken together, our study points to a cognitive mechanism of adaptive autonomy in which competitive interactions with other agents could promote both social cognition and volition in the form of non-stereotyped action choices., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Sexual functioning is an important predictor of well-being and relationship satisfaction. Previous research indicates that several aspects of cognitive function are related to sex-related behaviors and functioning among individuals with sex-related disorders, neurological disorders, and in older adults; however, this has been relatively underexamined in younger populations. To examine this, the present study assessed whether behavioral and/or neurophysiological measures of cognitive function are associated with sexual functioning in a community sample of young 489 adults (64 % female) ages 18-30. Cognitive flexibility (n = 460) and inhibition (n = 466) were measured using neuropsychological assessment (D-KEFS), and conflict monitoring and error monitoring were measured by event-related potentials (conflict N2: n = 394; error-related negativity: n = 389). After separately testing relations between the different measures of cognitive function and sexual functioning, we assessed whether results (1) remained after covarying for externalizing and internalizing dimensions (PID-5; n = 489) or (2) varied by gender. Finally, we tested whether any aspects of cognitive function were unique predictors of sexual functioning. Cognitive flexibility and error monitoring (i.e., error-related negativity) were both significantly related to sexual functioning among males and females, such that poorer cognitive flexibility and heightened error monitoring were related to lower sexual functioning. No significant effects emerged for inhibition or conflict monitoring. In a multiple regression model, cognitive flexibility and error monitoring each accounted for a unique portion of variance in sexual functioning beyond other aspects of cognitive function and psychopathology-related traits. Results suggest that cognitive function is a meaningful correlate of sexual functioning in young adulthood, which should be considered further in future research., Competing Interests: Declaration of competing interest The authors state that there is no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

An increasing number of studies have linked engagement in sport or increased physical fitness with improved cognitive performance. Additionally, studies have employed physical activity as an intervention to help with cognition in aging individuals. Despite this, the underlying mechanism (or mechanisms) by which benefits occur remain unclear. We investigated whether improved trainability for individuals engaged in sport or fitness training might underlie such benefits. Specifically, we assessed motor skill performance and learning rates in young adult runners, baseball players, and "control" individuals who did not regularly engage in sport or exercise using an implicit motor sequence learning task. Better initial performance on the task was seen for both the runner group and the baseball group but no benefits were seen for the baseball/runner groups for rates of improvement on the task. This was the case for both non-specific learning (or general motor skill learning-learning not associated with specific sequences of responses) and for sequence-specific learning (or improvement on repeated sequences of responses that participants were not aware of). This pattern may mean that either engagement in sport/physical activity results in improvements that are transferable beyond the context of the sport/training activity or that engagement in sport/exercise may relate to initial differences in the motor competence of an individual. Further work could beneficially investigate learning in more directly cognitive-related tasks and consolidation/improvement of performance over more prolonged time periods. Importantly, assessment of a fitness/sport intervention on performance and learning rates may provide a better context for some of the benefits reported in cross-sectional investigations of the effects of sport/fitness on cognition and aid in determining which differences are due to engaging in exercise and which differences affect the tendency for such engagement., (Copyright © 2024 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

The purpose of this study was to examine the mechanism by which social support influences mental wellbeing. Using the thriving through relationships model to provide a theoretical underpinning, cognitive flexibility was hypothesised as a mediator. Additionally, the research examined the consistency of this pathway between elite athletes, retired athletes, and non-athletes. Survey responses from a sample of 247 participants (n = 49 elite athletes, n = 61 retired athletes, n = 137 convenience sample; of which 127 (51.4%) were males were included in the analysis. Initial mediation analysis revealed a significant indirect pathway from social support to mental wellbeing through cognitive flexibility. Moderated mediation analysis revealed this pathway was significant for retired athletes and the convenience sample, but not for elite athletes. Results provide additional insight into the mechanisms by which social support influences wellbeing. Cognitive flexibility interventions may not be as effective for elite athletes., Competing Interests: Declaration of competing interest The authors report there are no competing interests to declare., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Cognitive control can be applied flexibly when task goals or environments change (i.e., cognitive flexibility), or stably to pursue a goal in the face of distraction (i.e., cognitive stability). Whether these seemingly contradictory characteristics have an inverse relationship has been controversial, as some studies have suggested a trade-off mechanism between cognitive flexibility and cognitive stability, while others have not found such reciprocal associations. This study investigated the possible antagonistic correlation between cognitive flexibility and stability using a novel version of the flexibility-stability paradigm and the classic cued task switching paradigm. In Experiment 1, we showed that cognitive flexibility was inversely correlated with cognitive stability, as increased distractor proportions were associated with decreased cognitive flexibility and greater cognitive stability. Moreover, cognitive flexibility and stability were regulated by a single control system instead of two independent control mechanisms, as the model selection results indicated that the reciprocally regulated model with one integration parameter outperformed all other models, and the model parameter was inversely linked to cognitive flexibility and stability. We found similar results using the classic cued task switching paradigm in Experiment 2. Therefore, a trade-off between cognitive flexibility and stability was observed from the paradigms used in this study., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: Parvalbumin (PV)-positive GABAergic (gamma-aminobutyric acidergic) cells provide robust perisomatic inhibition to neighboring pyramidal neurons and regulate brain oscillations. Alterations in PV interneuron connectivity and function in the medial prefrontal cortex have been consistently reported in psychiatric disorders associated with cognitive rigidity, suggesting that PV cell deficits could be a core cellular phenotype in these disorders. The p75 neurotrophin receptor (p75NTR) regulates the time course of PV cell maturation in a cell-autonomous fashion. Whether p75NTR expression during postnatal development affects adult prefrontal PV cell connectivity and cognitive function is unknown., Methods: We generated transgenic mice with conditional knockout of p75NTR in postnatal PV cells. We analyzed PV cell connectivity and recruitment following a tail pinch by immunolabeling and confocal imaging in naïve mice or following p75NTR re-expression in preadolescent or postadolescent mice using Cre-dependent viral vectors. Cognitive flexibility was evaluated using behavioral tests., Results: PV cell-specific p75NTR deletion increased both PV cell synapse density and proportion of PV cells surrounded by perineuronal nets, a marker of mature PV cells, in adult medial prefrontal cortex, but not visual cortex. Both phenotypes were rescued by viral-mediated reintroduction of p75NTR in preadolescent, but not postadolescent, medial prefrontal cortex. Prefrontal cortical PV cells failed to upregulate c-Fos following a tail-pinch stimulation in adult conditional knockout mice. Finally, conditional knockout mice showed impaired fear memory extinction learning as well as deficits in an attention set-shifting task., Conclusions: These findings suggest that p75NTR expression in adolescent PV cells contributes to the fine-tuning of their connectivity and promotes cognitive flexibility in adulthood., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Executive functions emerge throughout childhood and shape multiple cognitive and behavioral outcomes across the lifespan. Given the importance of these functions, there is considerable interest in understanding the role of environmental enrichment to support their development. The past 20 years have seen the emergence of a body of evidence around the beneficial effects of engaging in physical activity for executive functioning in children. Despite this, there are still unanswered questions, particularly about the confounding effects of the timing and dose of exercise-based interventions. During development, sensitive periods with heightened neural plasticity and sensitivity to environmental influences can offer an optimal time to introduce enrichment interventions. As such, sensitive periods for executive function could indicate an ideal time to introduce physical activity or be a potential confounder to study results if not considered. This narrative review discusses the potential presence of sensitive periods in preadolescent development where physical activity has greater benefits for executive function. Initially, we briefly review the largely parallel fields investigating the presence of sensitive periods for executive function and the effects of physical activity on executive function outcomes. We then bring together these 2 concepts to discuss the theoretical basis for developmentally sensitive periods during which children may be particularly amenable to physical activity-based interventions and offer potential ways forward to investigate this phenomenon. We hope this review will attract researchers to collaborate in the area and extend our current understanding of the development of executive functions as well as interventions like physical activity.