Search

In rodents and nonhuman primates, sex hormones are powerful modulators of dopamine neurotransmission. Yet little is known about hormonal regulation of the dopamine system in the human brain. Using Positron Emission Tomography (PET), we address this gap by comparing hormonal contraceptive users and non-users across multiple aspects of dopamine function: dopamine synthesis capacity via the PET radioligand 6-[18F]fluoro-m-tyrosine ([18F]FMT), baseline D2/3 receptor binding potential using [11C]raclopride, and dopamine release using methylphenidate-paired [11C]raclopride. Participants consisted of 36 healthy women (n=21 naturally cycling; n=15 hormonal contraceptive users), and men (n=20) as a comparison group. A behavioral index of cognitive flexibility was assessed prior to PET imaging. Hormonal contraceptive users exhibited greater dopamine synthesis capacity than naturally cycling participants, particularly in dorsal caudate, and greater cognitive flexibility. Further, across individuals the magnitude of striatal DA synthesis capacity was associated with cognitive flexibility. No group differences were observed in D2/3 receptor binding or dopamine release. Analyses by sex alone may obscure underlying differences in DA synthesis tied to women’s hormone status. Hormonal contraception (in the form of pill, shot, implant, ring or IUD) is used by ~400 million women worldwide, yet few studies have examined whether chronic hormonal manipulations impact basic properties of the dopamine system. Findings from this study begin to address this critical gap in women’s health.

Traumatic brain injury (TBI) is a leading cause of neurologic disability; the most common deficits affect prefrontal cortex-dependent functions such as attention, working memory, social behavior, and mental flexibility. Despite this prevalence, little is known about the pathophysiology that develops in frontal cortical microcircuits after TBI. We investigated whether alterations in subtype-specific inhibitory circuits are associated with cognitive inflexibility in a mouse model of frontal lobe contusion in both male and female mice that recapitulates aberrant mental flexibility as measured by deficits in rule reversal learning. Using patch-clamp recordings and optogenetic stimulation, we identified selective vulnerability in the non-fast-spiking and somatostatin-expressing (SOM+) subtypes of inhibitory neurons in layer V of the orbitofrontal cortex 2 months after injury. These subtypes exhibited reduced intrinsic excitability and a decrease in their synaptic output onto pyramidal neurons, respectively. By contrast, the fast-spiking and parvalbumin-expressing interneurons did not show changes in intrinsic excitability or synaptic output, respectively. Impairments in non-fast-spiking/SOM+ inhibitory circuit function were also associated with network hyperexcitability. These findings provide evidence for selective disruptions within specific inhibitory microcircuits that may guide the development of novel therapeutics for TBI. SIGNIFICANCE STATEMENT TBI frequently leads to chronic deficits in cognitive and behavioral functions that involve the prefrontal cortex, yet the maladaptive changes that occur in these cortical microcircuits are unknown. Our data indicate that alterations in subtype-specific inhibitory circuits, specifically vulnerability in the non-fast-spiking/somatostatin-expressing interneurons, occurs in the orbitofrontal cortex in the context of chronic deficits in reversal learning. These neurons exhibit reduced excitability and synaptic output, whereas the other prominent inhibitory population in layer V, the fast-spiking/parvalbumin-expressing interneurons as well as pyramidal neurons are not affected. Our work offers mechanistic insight into the subtype-specific function of neurons that may contribute to mental inflexibility after TBI.

The human dorsolateral prefrontal cortex (DLPFC; approximately corresponding to Brodmann areas 9 and 46) has demonstrable roles in diverse executive functions such as working memory, cognitive flexibility, planning, inhibition, and abstract reasoning. However, it remains unclear whether this is the result of one functionally homogeneous region or whether there are functional subdivisions within the DLPFC. Here, we divided the DLPFC into seven areas along rostral-caudal and dorsal-ventral axes anatomically and explored their respective patterns of structural and functional connectivity. In vivo probabilistic tractography (11 females and 13 males) and resting-state functional magnetic resonance imaging (fMRI; 57 females and 21 males) were employed to map out the patterns of connectivity from each DLPFC subregion. Structural connectivity demonstrated graded intraregional connectivity within the DLPFC. The patterns of structural connectivity between the DLPFC subregions and other cortical areas revealed that the dorsal-rostral subregions connections were restricted to other frontal and limbic areas, whereas the ventral-caudal region was widely connected to frontal, parietal, and limbic cortex. Functional connectivity analyses demonstrated that subregions of DLPFC were strongly interconnected to each other. The dorsal subregions were associated with the default mode network (DMN), while middle dorsal-rostral subregions were linked with the multiple demand network (MDN). The ventral-caudal subregion showed increased functional coupling with both DMN and MDN. Our results suggest that the connectivity of the DLPFC may be subdivided along a dorsorostral-ventrocaudal axis with differing (albeit graded) patterns of connectivity reflecting the integrative executive function of the DLPFC.SIGNIFICANCE STATEMENTResearch has shown that the dorsolateral prefrontal cortex (DLPFC) plays a role in various executive functions. By dividing the DLPFC into seven areas along rostral-caudal and dorsal-ventral axes anatomically, we explored their patterns of structural and functional connectivity. The patterns of connectivity within DLPFC subregions demonstrated graded intraregional connectivity. There were distinctive patterns of connectivity with other cortical areas in dorsal-rostral and ventral-caudal DLPFC subregions. Divisions across DLPFC subregions seem to align with their structural and functional connectivity. Our results suggest that DLPFC may be subdivided by the diagonal axis of the dorsal-ventral axis and rostral-caudal axis, supporting the framework of a functional organization along the anterior-posterior axis in the lateral PFC.

A common feature across neuropsychiatric disorders is inability to discontinue an action or thought once it has become detrimental. Reversal learning, a hallmark of executive control, requires plasticity within cortical, striatal and limbic circuits and is highly sensitive to disruption of N-methyl-(D)-aspartate receptor (NMDAR) function. In particular, selective deletion or antagonism of GluN2B containing NMDARs in cortical regions including the orbitofrontal cortex (OFC), promotes maladaptive perseveration. It remains unknown whether GluN2B functions to maintain local cortical activity necessary for reversal learning, or if it exerts a broader influence on the integration of neural activity across cortical and subcortical systems. To address this question, we utilized in vivo electrophysiology to record neuronal activity and local field potentials (LFP) in the orbitofrontal cortex and dorsal striatum (dS) of mice with deletion of GluN2B in neocortical and hippocampal principal cells while they performed touchscreen reversal learning. Reversal impairment produced by corticohippocampal GluN2B deletion was paralleled by an aberrant increase in functional connectivity between the OFC and dS. These alterations in coordination were associated with alterations in local OFC and dS firing activity. These data demonstrate highly dynamic patterns of cortical and striatal activity concomitant with reversal learning, and reveal GluN2B as a molecular mechanism underpinning the timing of these processes.

Cognitive flexibility describes the ability of animals to alter cognitively mediated behaviour in response to changing situational demands, and can vary according to prevailing environemental conditions and individual caracteristics. In the present study, we investigated (1) how learning and reversal learning performance changes between seasons, and (2) how cognitive flexibility is related to sex in a free-living small mammal. We studied 107 African striped mice, Rhabdomys pumilio, in an arid semi-desert, 58 during the hot dry summer with low food availability, and 49 during the cold wet winter with higher food availability. We used an escape box task to test for learning and reversal learning performance. We found that learning and reversal learning efficiency varied seasonally by sex: females tested in summer were faster at solving both learning and reversal tasks than males tested in winter. Performance varied within sex: males tested in winter showed faster learning compared to males tested in summer. During reversal learning, females tested in summer were more efficient and solve the task faster compared to females tested in winter. We suggest that seasonal cognitive performance could be related to sex-specific behavioural characteristics of the species, resulting in adaptation for living in harsh environmental conditions.

BACKGROUND Alcohol consumption during pregnancy can produce behavioral and cognitive deficits that persist into adulthood. These include impairments in executive functions, learning, planning, and cognitive flexibility. We have previously shown that moderate prenatal alcohol exposure (PAE) significantly impairs reversal learning, a measure of flexibility mediated across species by different brain areas that include the orbital frontal cortex (OFC). Reversal learning is likewise impaired by genetic or pharmacological inactivation of GluN2B subunit-containing N-methyl-D-aspartate receptors (NMDARs). In the current study, we tested the hypothesis that moderate PAE persistently alters the number and function of GluN2B subunit-containing NMDARs in OFC pyramidal neurons of adult mice. METHODS We used a rodent model of fetal alcohol spectrum disorders and left offspring undisturbed until adulthood. Using whole-cell, patch-clamp recordings, we assessed NMDAR function in slices from 90- to 100-day-old male and female PAE and control mice. Pharmacologically isolated NMDA receptor-mediated evoked excitatory postsynaptic currents (NMDA-eEPSCs) were recorded in the absence and presence of the GluN2B antagonist, Ro25-6981(1 µM). In a subset of littermates, we evaluated the level of GluN2B protein expression in the synaptic fraction using Western blotting technique. RESULTS Our results indicate that PAE females show significantly larger (~23%) NMDA-eEPSC amplitudes than controls, while PAE induced a significant decrease (~17%) in NMDA-eEPSC current density of pyramidal neurons recorded in slices from male mice. NMDA-eEPSC decay time was not affected in PAE-exposed mice from either sex. The contribution of GluN2B subunit-containing NMDARs to the eEPSCs was not significantly altered by PAE. Moreover, there were no significant changes in protein expression in the synaptic fraction of either PAE males or females. CONCLUSIONS These findings suggest that low-to-moderate PAE modulates NMDAR function in pyramidal neurons in a sex-specific manner, although we did not find evidence that the effect is mediated by dysfunction of synaptic GluN2B subunit-containing NMDARs.

Background Cognitive dysfunctions are increasing alarmingly around the world, and researchers are exploring preventive measures for improving brain performance. Pyrroloquinoline quinone (PQQ), a naturally occurring coenzyme in foods, exhibits potent antioxidant activity, and improves diverse functions which include mitochondrial activation, growth, repair, protection of nerve cells by increased expression of nerve growth factor (NGF) and NGF receptors; and suppression of fibril formation and aggregation of amyloid β. Objective This randomized, double-blind, placebo-controlled, parallel-group clinical investigation (RCT) evaluated the efficacy and safety of PQQ disodium salt powder (mnemoPQQ®) for improved cognitive function after 12 weeks of supplementation in healthy Japanese male and female (age 40 to Methods 64 healthy subjects were randomly assigned to receive either mnemoPQQ® (PQQ disodium salt: 21.5 mg/day) or a placebo over a period of 12 weeks. The efficacy of mnemoPQQ® on cognitive performance (memory, attention, judgment, and cognitive flexibility) was examined using Cognitrax as the primary outcome (primary endpoint), and forgetfulness questionnaire (DECO: Deterioration Cognitive Observee) and Mini-Mental State Examination-Japanese (MMSE-J) as the secondary outcome (secondary endpoint). Results A total of 58 subjects (placebo = 31; Age = 70.91 ± 3.06 Y; mnemoPQQ® group = 27; Age = 72.10 ± 3.77 Y) completed the study over a period of 12 weeks of supplementation. Significant improvements were observed on the Cognitrax's cognitive function domain score on "composite memory", "verbal memory", "reaction time", "complex attention", "cognitive flexibility", "executive function", and "motor speed" in the mnemoPQQ® group as compared to the placebo group. The DECO and the MMSE-J scores were also significantly improved in the mnemoPQQ® group. No adverse events were observed. Conclusions Study demonstrates that supplementation of PQQ disodium salt is useful in improving memory, attention, judgment, and cognitive function, in middle-aged to elderly population, who feel they have become more forgetful because of aging.

Aim To investigate longitudinal functional and neuropsychological outcomes 3–6 and 24 months after paediatric out-of-hospital cardiac arrest (OHCA). Further, to explore the association between paediatric cerebral performance category (PCPC) and intelligence. Methods Prospective longitudinal single center study including children (0–17 years) with OHCA, admitted to the PICU of a tertiary care hospital between 2012 and 2017. Survivors were assessed during an outpatient multidisciplinary follow-up program 3–6 and 24 months post-OHCA. Functional and neuropsychological outcomes were assessed through interviews, neurological exam, and validated neuropsychological testing. Results The total eligible cohort consisted of 49 paediatric OHCA survivors. The most common cause of OHCA was arrhythmia (33%). Median age at time of OHCA was 48 months, 67% were males. At 3–6 and 24 months post-OHCA, respectively 74 and 73% had a good PCPC score, defined as 1–2. Compared with normative data, OHCA children obtained worse sustained attention and processing speed scores 3–6 (n = 26) and 24 (n = 27) months post-OHCA. At 24 months, they also obtained worse intelligence, selective attention and cognitive flexibility scores. In children tested at both time-points (n = 19), no significant changes in neuropsychological outcomes were found over time. Intelligence scores did not correlate with PCPC. Conclusion Although paediatric OHCA survivors had a good PCPC score 3–6 and 24 months post-OHCA, they obtained worse scores on important neuropsychological domains such as intelligence and executive functioning (attention and cognitive flexibility). Follow-up should continue over a longer life span in order to fully understand the long-term impact of OHCA in childhood.

Cognitive flexibility is an essential prerequisite for goal-directed behavior, and daily observations already show that it deteriorates when one is engaged in a task for a (too) long time. Yet, the neural mechanisms underlying such fatigability effect in cognitive flexibility are poorly understood. We examined how theta, alpha, and beta frequency event-related synchronization and desynchronization processes during cued memory-based task switching are modulated by time-on-task effects. We put special emphasis on the examination of functional neuroanatomical regions being associated with these modulations, using EEG beamforming. We show clear declines in task switching performance (increased switch costs) with time on task. For processes occurring before rule switching or repetition processes, we show that anticipatory attentional sampling and selection mechanisms associated with fronto-parietal structures are modulated by time-on-task effects but sensory areas (occipital cortex) also show fatigability-dependent modulations. After target stimulus presentation, the allocation of processing resources for response selection as reflected by theta-related activity in parietal cortices is compromised with time on task and similarly a concomitant increase in alpha and beta band-related attentional processing or gating mechanisms in frontal and occipital regions. Yet, considering the behavioral data showing an apparent decline in performance, this probably compensatory increase is still insufficient to allow reasonable performance. The same is likely the case for processes occurring before rule switching or repetition processes. Comparative analyses show that modulations of alpha band activity are as strongly modulated by fatigability as theta band activity. Implications of these findings for theoretical concepts on fatigability are discussed.

OBJECTIVES Perceived racial discrimination is associated with depressive symptoms for African American adults; however, insight to protective factors for racism and depression in African Americans is limited. While current research suggests that dispositional forgiveness is an important factor in how people perceive and cope with interpersonal transgressions, few studies have examined its role in the context of racial discrimination. The purpose of this study was to examine the moderating effect of forgiveness (beyond broader internalized religiosity) on the association between perceived racial discrimination and depressive symptoms in African American adults. METHOD Sample included 101 African American adults (60.2% female; Mage = 21.90 years, SD = 4.93 years) who endorsed experiences of racial discrimination. Participants completed a questionnaire battery consisting of self-report measures of perceived experiences of racial discrimination, depression, dispositional forgiveness, and intrinsic religiosity. RESULTS Regression analyses showed dispositional forgiveness moderated the association between perceived racial discrimination and symptoms of depression above and beyond intrinsic religiosity (β = -.05, 95% CI [-.10, -.05], p < .05), such that the racial discrimination-depression association was significant for participants who reported low levels of dispositional forgiveness, but not for individuals who reported higher levels of dispositional forgiveness. CONCLUSIONS These findings provide insight into the role of dispositional forgiveness in experiences of racial discrimination and suggest that cognitive flexibility serves as an adaptive coping strategy to experiencing discrimination. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

With rates of psychiatric illnesses such as depression continuing to rise, additional preclinical models are needed to facilitate translational neuroscience research. In the current study, the raccoon (Procyon lotor) was investigated due to its similarities with primate brains, including comparable proportional neuronal densities, cortical magnification of the forepaw area, and cortical gyrification. Specifically, we report on the cytoarchitectural characteristics of raccoons profiled as high, intermediate, or low solvers in a multi-access problem-solving task. Isotropic fractionation indicated that high-solvers had significantly more cells in the hippocampus (HC) than the other solving groups; further, a nonsignificant trend suggested that this increase in cell profile density was due to increased non-neuronal (e.g., glial) cells. Group differences were not observed in the cellular density of the somatosensory cortex. Thionin-based staining confirmed the presence of von Economo neurons (VENs) in the frontoinsular (FI) cortex, although no impact of solving ability on VEN cell profile density levels was observed. Elongated fusiform cells were quantified in the hippocampus dentate gyrus where high-solvers were observed to have higher levels of this cell type than the other solving groups. In sum, the current findings suggest that varying cytoarchitectural phenotypes contribute to cognitive flexibility. Additional research is necessary to determine the translational value of cytoarchitectural distribution patterns on adaptive behavioral outcomes associated with cognitive performance and mental health. This article is protected by copyright. All rights reserved.

Numerous studies have supported benefits of omega-3 supplementation using Menhaden fish oil (FO) to promote brain maturation and plasticity during critical developmental periods. The goal of this study was to determine sex-specific immediate and delayed impact of adolescent omega-3 supplementation on visuospatial memory and cognitive flexibility. Sixty-four Wistar rats (n = 32 males and females) received daily FO or soybean oil (CSO) supplementation via oral gavage (0.3 mL/100 g body weight) from postnatal day 28–47. The Barnes Maze Test (BMT) was used to measure visuospatial memory and reversal learning trials (RL) determined cognitive flexibility. Juveniles underwent testing immediately after the gavage period, while adults began testing on postnatal day 90. Adult rats showed reduced working memory errors (WME) and gradual decrease in escape latencies compared to juveniles. Importantly, adult FO-supplemented females displayed fewer WME than males, while males’ performance benefited from CSO supplementation. Overall, sex- and supplementation-dependent effects supported a positive impact of FO in female rats only. Our findings support the potential for supplementation limited to the early adolescence period to influence adulthood spatial learning and cognitive flexibility in a sex-specific manner.

The effects of digital Cognitive Behavior Therapy for insomnia (dCBT-i) on sleep quality have been previously demonstrated but the spillover effects on fatigue, flow (a state of immersion in activities of interest), and cognitive flexibility remain unclear. The current study examined the effectiveness of dCBT-i. A total of 97 college students (20.96 ± 1.87 years, 73.1% female students) were randomly selected from a shortlist and divided into sleep intervention (n = 39), conventional education (n = 37), and healthy control (n = 21) groups. Task switching paradigm, Fatigue Severity Scale (FSS), Flow Experience Scale (FES), and the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI) were measured pre- and post-intervention. Results show that the sleep quality of the intervention group improved, and fatigue was relieved. Participants in the sleep intervention group had increased flow experience scores post-intervention and improved cognitive flexibility. The control group’s sleep quality deteriorated and fatigue level increased. dCBT-i can not only achieve a significant improvement in sleep quality and reduce fatigue, but also improve learning abilities, quality of life, flow, and cognitive flexibility. Future research should pay attention to indicators such as work efficiency, sedative use, and the durability and stability of such effects.

Objective Computational models provide information about cognitive components underlying behavior. When applied to psychopathology-relevant processes, they offer additional insight to observed differences in behavioral performance. Drift diffusion models have been successfully applied to investigate processing efficiency during binary choice tasks. Using these models, we examine the association between psychopathology (irritability and inattention/hyperactivity) and processing efficiency under different attentional demands. Method A total of 187 youths with attention-deficit/hyperactivity disorder (ADHD), disruptive mood dysregulation disorder (DMDD), both disorders, or no major psychopathology (age, mean ± SD, 13.09 ± 2.55 y, 34% female) completed an Eriksen Flanker task. Of these, 87 youths provided complete data on dimensional measures of the core symptom of DMDD (irritability) and those of ADHD (inattention and hyperactivity). Results In a categorical diagnosis-based analysis (n = 187), we found significant interactive effects among ADHD, DMDD, and task condition on processing efficiency, whereby changes in processing efficiency between conflict and nonconflict conditions were larger in youths without psychopathology compared with patients. Analysis of symptom severity (n = 87) across diagnoses similarly revealed an interaction between symptom dimensions and task condition on processing efficiency. Irritability moderated the magnitude of association between inattention symptoms and difference in processing efficiency between conflict and nonconflict conditions. Conclusion Adapting processing efficiency to cognitive demands may represent a shared cognitive endophenotype for both ADHD and DMDD. Highly irritable and/or inattentive youth may have difficulty adjusting processing efficiency to changing task demands, possibly reflecting impairments in cognitive flexibility.

BACKGROUND: Diet, in particular the Mediterranean diet, has been associated with better cognitive function and less cognitive decline in older populations.OBJECTIVES: To quantify associations of a healthy diet, defined by adherence to either the Mediterranean diet, the WHO guidelines, or Dutch Health Council dietary guidelines, with cognitive function and cognitive decline from middle age into old age.METHODS: From the Doetinchem Cohort Study, a large population-based longitudinal study, 3644 participants (51% females) aged 45-75 y at baseline, were included. Global cognitive function, memory, processing speed, and cognitive flexibility were assessed at 5-y time intervals up to 20-y follow-up. Adherence to the Mediterranean diet was measured with the modified Mediterranean Diet Score (mMDS), adherence to the WHO dietary guidelines with the Healthy Diet Indicator (HDI), and adherence to the Dutch Health Council dietary guidelines 2015 with the modified Dutch Healthy Diet 2015 index (mDHD15-index). The scores on the dietary indices were classified in tertiles (low, medium, high adherence). Linear mixed models were used to model level and change in cognitive function by adherence to healthy diets.RESULTS: The highest tertiles of the mMDS, HDI, and mDHD15-index were associated with better cognitive function compared with the lowest tertiles (P values CONCLUSIONS: Healthier dietary habits, determined by higher adherence to dietary guidelines, are associated with better cognitive function and slower cognitive decline with aging from middle age onwards.

Ayahuasca is a plant concoction containing N,N-dimethyltryptamine (DMT) and certain β-carboline alkaloids from South America. Previous research in naturalistic settings has suggested that ingestion of ayahuasca can improve mental health and well-being; however, these studies were not placebo controlled and did not control for the possibility of expectation bias. This naturalistic observational study was designed to assess whether mental health changes were produced by ayahuasca or by set and setting. Assessments were made pre- and post-ayahuasca sessions in 30 experienced participants of ayahuasca retreats hosted in the Netherlands, Spain, and Germany. Participants consumed ayahuasca (N = 14) or placebo (N = 16). Analysis revealed a main effect of time on symptoms of depression, anxiety, and stress. Compared to baseline, symptoms reduced in both groups after the ceremony, independent of treatment. There was a main treatment × time interaction on implicit emotional empathy, indicating that ayahuasca increased emotional empathy to negative stimuli. The current findings suggest that improvements in mental health of participants of ayahuasca ceremonies can be driven by non-pharmacological factors that constitute a placebo response but also by pharmacological factors that are related to the use of ayahuasca. These findings stress the importance of placebo-controlled designs in psychedelic research and the need to further explore the contribution of non-pharmacological factors to the psychedelic experience.

Background: Myelin damage is a salient feature in cerebral small vessel disease (cSVD). Of note, myelin damage extends into the normal appearing white matter (NAWM). Currently, the specific role of myelin content in cognition is poorly understood. Objective: The objective of this exploratory study was to investigate the association between NAWM myelin and cognitive function in older adults with cSVD. Methods: This exploratory study included 55 participants with cSVD. NAWM myelin was measured using myelin water imaging and was quantified as myelin water fraction (MWF). Assessment of cognitive function included processing speed (Trail Making Test Part A), set shifting (Trail Making Test Part B minus A), working memory (Verbal Digit Span Backwards Test), and inhibition (Stroop Test). Multiple linear regression analyses assessed the contribution of NAWM MWF on cognitive outcomes controlling for age, education, and total white matter hyperintensity volume. The overall alpha was set at ≤0.05. Results: After accounting for age, education, and total white matter hyperintensity volume, lower NAWM MWF was significantly associated with slower processing speed (β = –0.29, p = 0.037) and poorer working memory (β= 0.30, p = 0.048). NAWM MWF was not significantly associated with set shifting or inhibitory control (p > 0.132). Conclusion: Myelin loss in NAWM may play a role in the evolution of impaired processing speed and working memory in people with cSVD. Future studies, with a longitudinal design and larger sample sizes, are needed to fully elucidate the role of myelin as a potential biomarker for cognitive function.

BACKGROUND: The burden of post-stroke cognitive impairment, as well as affective disorders, remains persistently high. With improved stroke survival rates and increasing life expectancy, there is a need for effective interventions to facilitate remediation of neurocognitive impairments and post-stroke mood disorders. OBJECTIVE: To investigate the effects of Therapeutic Instrumental Music Performance (TIMP) training with and without Motor Imagery on cognitive functioning and affective responding in chronic post-stroke individuals. METHODS: Thirty chronic post-stroke, community-dwelling participants were randomized to one of three experimental arms: (1) 45 minutes of active TIMP, (2) 30 minutes of active TIMP followed by 15 minutes of metronome-cued motor imagery (TIMP+cMI), (3) 30 minutes of active TIMP followed by 15 minutes of motor imagery without cues (TIMP+MI). Training took place three times a week for three weeks, using a selection of acoustic and electronic instruments. Assessments, administered at two baselines and post-training, included the Trail Making Test (TMT) - Part B to assess mental flexibility, the Digit Span Test (DST) to determine short-term memory capacity, the Multiple Affect Adjective Checklist - Revised (MAACL-R) to ascertain current affective state, and the General Self-Efficacy Scale (GSE) to assess perceived self-efficacy. The Self-Assessment Maniqin (SAM) was also administered prior to and following each training session. RESULTS: Thirty participants completed the protocol, ten per arm [14 women; mean age = 55.9; mean time post-stroke = 66.9 months]. There were no statistically significant differences between pooled group baseline measures. The TIMP+MI group showed a statistically significant decrease in time from pre-test 2 to post-test on the TMT. The TIMP group showed a significant increase on MAACL sensation seeking scores, as well as on the Valence and Dominance portions of the SAM; TIMP+cMI showed respective increases and decreases in positive and negative affect on the MAACL, and increases on the Valence, Dominance, and Arousal portions of the SAM. No statistically significant association between cognitive and affective measures was obtained. CONCLUSIONS: The mental flexibility aspect of executive functioning appears to be enhanced by therapeutic instrumental music training in conjunction with motor imagery, possibly due to multisensory integration and consolidation of representations through motor imagery rehearsal following active practice. Active training using musical instruments appears to have a positive impact on affective responding; however, these changes occurred independently of improvements to cognition.

Background Latent inhibition (LI) reflects an adaptive form of learning impaired in certain forms of mental illness. Glutamate receptor activity is linked to LI, but the potential role of synaptic plasticity remains unspecified. Methods Accordingly, the present study examined the possible role of long-term depression (LTD) in LI induced by prior exposure of rats to an auditory stimulus used subsequently as a conditional stimulus to signal a pending footshock. We employed 2 mechanistically distinct LTD inhibitors, the Tat-GluA23Y peptide that blocks endocytosis of the GluA2-containing glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, or the selective glutamate n-methyl-d-aspartate receptor 2B antagonist, Ro25-6981, administered prior to the acquisition of 2-way conditioned avoidance with or without tone pre-exposure. Results Systemic LTD blockade with the Tat-GluA23Y peptide strengthened the LI effect by further impairing acquisition of conditioned avoidance in conditional stimulus-preexposed rats compared with normal conditioning in non-preexposed controls. Systemic Ro25-6981 had no significant effects. Brain region–specific microinjections of the Tat-GluA23Y peptide into the nucleus accumbens, medial prefrontal cortex, or central or basolateral amygdala demonstrated that disruption of glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor endocytosis in the central amygdala also potentiated the LI effect. Conclusions These data revealed a previously unknown role for central amygdala LTD in LI as a key mediator of cognitive flexibility required to respond to previously irrelevant stimuli that acquire significance through reinforcement. The findings may have relevance both for our mechanistic understanding of LI and its alteration in disease states such as schizophrenia, while further elucidating the role of LTD in learning and memory.

Cerebrovascular lesions are widely prevalent in patients with Alzheimer’s disease (AD), but their relationship to the pathophysiology of AD remains poorly understood. An improved understanding of the interaction of cerebrovascular damage with AD is crucial for the development of therapeutic approaches. Herein, we investigated the effects of chronic cerebral hypoperfusion (CCH) in a 5XFAD transgenic (Tg) mouse model of AD. We established CCH conditions in both Tg and non-Tg mice by inducing unilateral common carotid artery occlusion (UCCAO). Cognitive performance in mice was evaluated, and their brain tissue was examined for amyloid-beta (Aβ) pathology to elucidate possible mechanisms. We found that UCCAO-operated Tg mice showed impaired cognitive flexibility in the reversal phase of the hidden-platform water maze task compared to sham-operated Tg mice. Interestingly, UCCAO-operated Tg mice used fewer spatial cognitive strategies than sham-operated Tg mice during reversal learning. These cognitive deficits were accompanied by increased Aβ plaque burden and Aβ42 levels in the hippocampus and prefrontal cortex, 2 regions that play essential roles in the regulation of cognitive flexibility. Furthermore, changes in cognitive flexibility are strongly correlated with the expression levels of enzymes related to Aβ clearance, such as neprilysin and insulin-degrading enzymes. These findings suggest that, in 5XFAD mice, impaired cognitive flexibility is related to CCH, and that Aβ clearance might be involved in this process.

Preterm birth is a principal cause of neurological disability later in life, including cognitive and behavioral deficits. Notably, cognitive impairment has greater impact on quality of life than physical disability. Survivors of preterm birth commonly have deficits of executive function. Difficulties with tasks and planning complexity correlate positively with increasing disability. To overcome these barriers for children born preterm, preclinical and clinical studies have emphasized the importance of neurorestoration. Erythropoietin (EPO) is a endogenous cytokine with multiple beneficial mechanisms of action following perinatal brain injury. While most preclinical investigations have focused on pathology and molecular mechanisms, translational studies of repair using clinically viable biobehavioral biomarkers are still lacking. Here, using an established model of encephalopathy of prematurity secondary to placental insufficiency, we tested the hypothesis that administration of EPO in the neonatal period would attenuate deficits in recognition memory and cognitive flexibility in adult rats of both sexes. We assessed cognition and executive function in two ways. First, using the classic test of novel object recognition and second, using a touchscreen platform. Touchscreen testing allows for rigorous testing of cognition and executive function in preclinical and clinical scenarios. Data show that adult rats exhibit deficits in recognition memory and cognitive flexibility following in utero placental insufficiency. Notably, neonatal treatment of EPO attenuates these deficits in adulthood and facilitates functional repair. Together, these data validate EPO neurorestoration using a clinically relevant outcome measure and support the concept that postnatal treatment following in utero injury can improve cognition and executive function through adulthood.

Early life stress (ELS) followed by pediatric mild traumatic brain injury (mTBI) negatively impacts spatial learning and memory and increases microglial activation in adolescent rats, but whether the same paradigm negatively affects higher order executive function is not known. Hence, we utilized the attentional set-shifting test (AST) to evaluate executive function (cognitive flexibility) and to determine its relationship with neuroinflammation and hypothalamic–pituitary–adrenal (HPA) axis activity after pediatric mTBI in male rats. ELS was induced via maternal separation for 180 min per day (MS180) during the first 21 post-natal (P) days, while controls (CONT) were undisturbed. At P21, fully anesthetized rats received a mild controlled cortical impact (2.2 mm tissue deformation at 4 m/sec) or sham injury. AST was evaluated during adolescence on P35–P40 and cytokine expression and HPA activity were analyzed on P42. The data indicate that pediatric mTBI produced a significant reversal learning deficit on the AST versus sham (p 0.05), it did result in increased hippocampal neuroinflammation relative to mTBI (p

Supplemental digital content is available in the text., Purpose The aim of this study was to investigate the indirect effects of cardiorespiratory fitness on scholastic performance through executive functions. More precisely, we examined the contribution of the different domains of executive functions, and whether this relationship was specific to certain school topics. Methods Children 8–12 yr old completed nine cognitive tests and the multistage fitness test. Structural equation modeling techniques were used to analyze the role of different domains of executive functions (inhibition, working memory, cognitive flexibility, and a common factor to all tasks) in the relationship between cardiorespiratory fitness and school grades in three domains: (i) mathematics; (ii) grammar, spelling, and vocabulary; and (iii) text comprehension and expression. Covariate analyses included age and socioeconomic status. Results The results of this study showed that an indirect effect of the various domains of executive functions explained, in part, the relationship between cardiorespiratory fitness and (i) mathematics (β = 0.12, SE = 0.03, P < 0.001), and between cardiorespiratory fitness and (ii) grammar, spelling, and vocabulary (β = 0.12, SE = 0.03, P < 0.001). No relationship between cardiorespiratory fitness and (iii) text comprehension and expression was observed. Although executive functions correlated with school grades, cognitive flexibility drove the indirect effect when all executive function domains were simultaneously taken into account. Conclusions These results show the role that executive functions play in understanding the relationship between cardiorespiratory fitness and scholastic performance. Importantly, not all executive function domains contributed equally because cognitive flexibility played a leading role in this wide age range. Furthermore, the relationship between cardiorespiratory fitness and scholastic performance was strongest for mathematics and for low-level language topics but nonsignificant for higher-level language topics, providing a more modulated view of the effect of cardiorespiratory fitness on language.

OBJECTIVES The purpose of the study was to test the hypothesis that anticholinergic drug exposure is associated with cognitive decline in the Wisconsin Registry for Alzheimer's Prevention (WRAP) study. Secondary aims were to assess if the effects of anticholinergic drugs on different domains of cognitive functioning varied for the entire sample and by apolipoprotein e4 status. METHODS The WRAP study includes a sample of 1,573 subjects who self-reported medication use and were administered several cognitive tests four times over a decade. Partial correlations assessed relationships between reported days of definite anticholinergic drug exposure with changes in cognitive performance. Linear mixed models were conducted testing main effects for anticholinergic drug use and interaction effects between anticholinergic drug use, apolipoprotein e4 status, and time on neuropsychological assessment performance. RESULTS Partial correlations indicated that days of anticholinergic drug exposure was associated with a decline in mental status for the entire sample (r = -.043, p = .011), and immediate verbal memory (r = -.066, p = .043), delayed verbal memory (r = -.077, p = .018), psychomotor speed (r = -.066, p = .043), and cognitive flexibility (r = -.067, p = .040) of apolipoprotein e4 carriers only. The linear mixed-model results suggested that anticholinergic drug users had a greater decline than nonusers in delayed memory, psychomotor speed, and cognitive flexibility. Apolipoprotein e4 carrier, anticholinergic drug users performed worse in delayed memory than nonusers and noncarrier, anticholinergic drug users. CONCLUSIONS Anticholinergic drug use may have deleterious effects on the cognitive functioning of subjects in populations at risk for dementia, especially among apolipoprotein e4 carriers. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The goal of this study was to examine reciprocal associations between cognitive flexibility and externalizing and internalizing behavior problems longitudinally using data on four occasions from kindergarten through first grade and test for potential gender differences in these associations. The Dimensional Change Card Sort task was used to assess children’s cognitive flexibility as a measure of executive function. Participants were 12,462 kindergarteners (49% female) from the Early Childhood Longitudinal Study (ECLS-K: 2011). Results from multivariate latent curve models with structured residuals revealed that children’s cognitive flexibility at the beginning of kindergarten was not associated with their growth in either externalizing (r = -0.01, p = .174), or internalizing (r = -0.03, p = .403) problems between kindergarten and the end of first grade. However, after controlling for individual differences in growth, cognitive flexibility at each assessment directly contributed to subsequent lower levels of internalizing (but not externalizing) behavior problems at the next assessment (b = -0.004, p = 0.013; β = -0.03), suggesting that children who are more flexible in switching from one activity to another may be less prone to developing internalizing problems. At kindergarten entry boys had lower levels of cognitive flexibility (b = -0.31, p

One of the key challenges in assessing cognitive performance is to detect not only apparent impairment but to also pick up on subtle differences. Computerized tests benefit especially from the acquisition of fine-grained outcome measures. However, the equivalency of paper-based and computerized tests cannot be assumed. The Trail-Making-Test is a paper-pencil cognitive assessment tool (ppTMT) that has been used in many research studies to evaluate visuomotor abilities and mental flexibility. A digital version of the extended TMT (including a condition measuring fine motor speed) called the dTMT has been developed. This study aims to test (1) reliability, (2) equivalence, and (3) agreement of the ppTMT and dTMT. A total of 53 healthy individuals aged 19 to 82 years of age (22 men, 31 women; mean age 42.2, SD = 22.8) completed three trials per ppTMT and dTMT condition. Part M involves following a predefined path, Part A links numbers randomly distributed in space, in ascending order, and Part B alternates between linking numbers and letters. dTMT scores were highly reproducible, correlated strongly with paper-pencil administered durations, and discriminated young from older adults. Measures of reliability, sensitivity, and clinical meaning for dTMT scores were favorable compared with ppTMT-based testing. Our findings support the comparability of TMT-indices in computerized assessments. While many digital biomarker efforts are in progress (e.g., neurodegenerative disorders), the dTMT sets itself apart through its high sensitivity, the alternate forms, and the additional component measures. In this light, it could serve as a starting point for an early diagnostic tool.

Cognitive inflexibility is one of the major clinical symptoms of post-traumatic stress disorder (PTSD). Studies have examined the impact of traumatic events on anxiety. However, there were limited reports on the effect of traumatic episodes on cognitive flexibility. Therefore, animal models developing cognitive inflexibility would provide new insight of pathophysiology and pharmacotherapy of PTSD. Male Wistar rats were subjected to stress–re-stress (SRS) procedure by restraining them for 2 h followed by foot shock (FS) and halothane exposure on day 2 (D-2). Then, the rats were exposed every week to FS as re-stress cue up to D-32. Donepezil (3 mg/kg; po) and sertraline (10 mg/kg; po) dosing was started from D-8 and continued up to D-32. SRS exposure caused cognitive inflexibility by producing deficits in intra-dimension (ID) and extra-dimension (ED) set-shifting which was significantly attenuated by donepezil. However, sertraline mitigated only ID shift in SRS-subjected rats. SRS-induced PTSD-like symptoms such as fear response, anxiety-like behaviour and cognitive deficits were attenuated by both donepezil and sertraline. Donepezil did not modulate the SRS-induced hypothalamic–pituitary–adrenal (HPA) axis dysfunction and activation of serotonergic and nor-adrenergic system. Interestingly, exposure of SRS caused a decrease in acetylcholine level and increase in acetylcholine esterase activity in prefrontal cortex (PFC) and hippocampus (HIP) which was only mitigated by donepezil. Donepezil significantly attenuated SRS-induced down-regulation of choline-acetyl transferase and α-7 nicotinic acetylcholine receptor expressions in PFC and HIP. Cognitive inflexibility is developed in the SRS model along with other PTSD-like symptoms which were attenuated by donepezil.

Empathy encompasses the ability to contemplate and vicariously share in the emotional life of others, and is critical for social interaction, and may enhance subjective happiness. OBJECTIVE While a few theoretical models propose that executive function may play a role in empathy, it is unknown how variation in executive function, and underlying variation in key large-scale brain network nodes, such as the dorsolateral prefrontal cortex node within the executive control network-or the medial prefrontal cortex (PFC) node within the mentalizing/theory of mind network-may account for individual differences in empathy capacity. METHOD The relationship between individual differences in executive capacity-parsed into working memory, inhibition, and cognitive flexibility subdomains-and magnitude of activity in a priori identified PFC subregions during a functional MRI-based ecologically valid empathy induction paradigm, was investigated. Empathic happiness (i.e., vicarious joy) and empathic concern (i.e., vicarious sadness) in response to the life circumstances of actual people were measured at separate time points as brain functional MRI was obtained. Participants also completed executive-heavy clinical neuropsychological tasks outside of the scanner. RESULTS Frontopolar PFC was activated across both types of empathy. However, empathic happiness related to engagement of a much broader network of prefrontal cortex subregions relative to empathic concern: spawning frontopolar, dorsolateral, and medial aspects. PFC activation during both types of empathy was positively predicted by working memory capacity. CONCLUSION Activation in core aspects of the working memory-executive control network, and core happiness-related aspects of the mentalizing brain network (i.e., medial PFC and precuneus) predicted greater empathy capacity. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Psychological androgyny has long been associated with greater cognitive flexibility, adaptive behavior, and better mental health, but whether a similar concept can be defined using neural features remains unknown. Using the neuroimaging data from 9620 participants, we found that global functional connectivity was stronger in the male brain before middle age but became weaker after that, when compared with the female brain, after systematic testing of potentially confounding effects. We defined a brain gender continuum by estimating the likelihood of an observed functional connectivity matrix to represent a male brain. We found that participants mapped at the center of this continuum had fewer internalizing symptoms compared with those at the 2 extreme ends. These findings suggest a novel hypothesis proposing that there exists a neuroimaging concept of androgyny using the brain gender continuum, which may be associated with better mental health in a similar way to psychological androgyny.

Objectives Cardiovascular disease is disproportionally prevalent in bipolar disorder (BD) and has been linked to cognition in preliminary studies. Herein we evaluate the association between known risk factors for cardiovascular disease and executive function in BD patients compared to healthy controls. Methods In a sample of n=57 individuals (n=23 BD, n=34 controls) we assessed two subdomains of executive function; cognitive flexibility (using the Trail Making Test - Part B) and cognitive inhibition (using the Stroop Colour Word Interference Task). Cardiovascular risk was assessed by means of serum triglyceride levels, body mass index (BMI) and waist circumference, as well as dietary saturated fat intake and a sex-specific cumulative cardiovascular risk score calculated using the Framingham Heart Study method. Results Patients with BD had higher BMI and waist circumference, with more BD patients categorized as having central obesity than controls. In the BD group only, higher triglyceride levels were associated with worse cognitive flexibility, and elevated cumulative cardiovascular disease risk was associated with worse cognitive inhibition. No correlations between cardiovascular risk factors and executive function were evident in the control group. Limitations The study was limited by the small sample size and should be considered hypothesis-generating Conclusions The associations between triglyceride levels, cumulative cardiovascular disease risk and executive functioning evident in BD in this study preliminarily indicate the potential for mechanistic overlap of physical health and cognitive function in the disorder.

Executive functions (EFs) are essential for student's learning and classroom functioning. The current cluster randomized controlled trial examines the effects of mindfulness intervention vs. active control program (i.e., relaxation) focusing on the main EFs (i.e., working memory, response inhibition, cognitive processing, cognitive flexibility and verbal fluency). A total of 131 students from 6th grade and 8th grade (median age 12 and 15) from four comprehensive schools participated. The schools were to equal shares randomized to intervention and active control groups, i.e., groups who underwent a 9-week mindfulness practice or relaxation program, respectively. Participants completed a cognitive test-package at baseline/pre-intervention, post-intervention at 9 weeks and follow-up at 6 months. Both intervention and active relaxation-based control groups improved on a majority of EF measures at both 9 weeks and 6 months. There was no significant difference between the mindfulness intervention group and the active control program in EFs. The current study suggests that mindfulness intervention and active control program do not differ in their effects to EFs, although both may have positive outcomes. Further research with both active and inactive control groups is needed to map the potential benefits of similar programs for cognitive functioning. CC BY-NC-ND 4.0

Sports provide a context where important aspects of children’s health, such as motor skills and cognitive functions, can be enhanced. However, it is unknown which type of sport may be better for the development of motor competence (MC) and executive functions (EFs). This study investigated potential differences in MC and EFs in boys and girls, being involved in different types of sports (team, individual open skill, individual closed skill). A total of 115 children (49 boys), 8–12 years old (10.30 ± 1.19 years), participated in the study. Their MC was assessed with the Bruininks–Oseretsky Test of Motor Proficiency-2 Short Form, whereas for EFs, the Attention Network Test, the digits backwards test, and the how many–what number test were utilized. Significant MC differences among participants in different types of sports were revealed, favoring those from closed-skill sports; nevertheless, their EFs were at similar levels. Furthermore, no significant gender MC and EFs differences were detected. It seems that children’s participation in specific types of sports differentiates their motor skills but not their EFs, whereas boys and girls, when provided with the same opportunities, present similar levels of MC and EFs.

PURPOSE: There is a general lack of evidence on the efficacy of rehabilitation training methods after childhood stroke. The aim of the current paper is to provide an example of a multidisciplinary assessment and intensive patient-centered rehabilitation program that was devised following the Clinical Guidelines for Childhood Stroke Diagnosis, Management and Rehabilitation, based on the International Classification of Functioning, Disability and Health. METHOD: The case of a 13-year-old teenager with physical, linguistic, cognitive and emotional impairments after acute ischemic stroke (AIS) in left middle cerebral artery territories is presented and his neurorehabilitation program is described. RESULTS: After an intensive and comprehensive rehabilitation period, the patient showed significant improvement involving language abilities, cognitive flexibility, logical reasoning and motor independence. A 6-month post-stroke follow-up evaluation showed further gains in spontaneous language, improved motivation and collaboration, reduction of impulsiveness and better general motor stability. CONCLUSION: This case highlights how an intensive, patient-centered, interdisciplinary rehabilitation approach can lead to good improvement across different domains, maximizing the spontaneous recovery in children and adolescents after AIS.

Depression is a debilitating disorder that often starts manifesting in early childhood and peaks in onset during adolescence. Neurocognitive impairments have emerged as clinically important characteristics of depression, but it remains controversial which domains specifically index pre-existing vulnerability, state-related or trait-related markers. Here, we disentangled these effects by analysing the Adolescent Brain Cognitive Development dataset (n = 4626). Using information of participants’ current and past mental disorders, as well as family mental health history, we identified low-risk healthy (n = 2100), high-risk healthy (n = 2023), remitted depressed (n = 401) and currently depressed children (n = 102). Factor analysis of 11 cognitive variables was performed to elucidate latent structure and canonical correlation analyses conducted to probe regional brain volumes reliably associated with the cognitive factors. Bayesian model comparison of various a priori hypotheses differing in how low-risk healthy, high-risk healthy, remitted depressed and currently depressed children performed in various cognitive domains was performed. Factor analysis revealed three domains: language and reasoning, cognitive flexibility and memory recall. Deficits in language and reasoning ability, as well as in volumes of associated regions such as the middle temporal and superior frontal gyrus, represented state- and trait-related markers of depression but not pre-existing vulnerability. In contrast, there was no compelling evidence of impairments in other domains. These findings—although cross-sectional and specific to 9–10-year-old children—might have important clinical implications, suggesting that cognitive dysfunction may not be useful targets of preventive interventions. Depressed patients, even after remission, might also benefit from less commonly used treatments such as cognitive remediation therapy.

The brain’s capacity to process unexpected events is key to cognitive flexibility. The most well-known effect of unexpected events is the interruption of attentional engagement (distraction). We tested whether unexpected events interrupt attentional representations by activating a neural mechanism for inhibitory control. This mechanism is most well characterized within the motor system. However, recent work showed that it is automatically activated by unexpected events and can explain some of their nonmotor effects (e.g., on working memory representations). Here, human participants attended to lateralized flickering visual stimuli, producing steady-state visual evoked potentials (SSVEPs) in the scalp electroencephalogram. After unexpected sounds, the SSVEP was rapidly suppressed. Using a functional localizer (stop-signal) task and independent component analysis, we then identified a fronto-central EEG source whose activity indexes inhibitory motor control. Unexpected sounds in the SSVEP task also activated this source. Using single-trial analyses, we found that subcomponents of this source differentially relate to sound-induced SSVEP changes: While its N2 component predicted the subsequent suppression of the attended-stimulus SSVEP, the P3 component predicted the suppression of the SSVEP to the unattended stimulus. These results shed new light on the processes underlying fronto-central control signals and have implications for phenomena such as distraction and the attentional blink.

The widespread deficits in cognitive flexibility observed across psychiatric disorders call for improved rodent tests to understand the biology of cognitive flexibility and development of better psychotherapeutics. Current reversal learning paradigms have a forced-choice setup that challenges the interpretation of results. We aimed at developing a free-choice reversal learning test, where images are presented sequentially and animals are free to move, to enable investigation of the cognitive sub-processes that occur during reversal. Behavior in female C57BL/6JOlaHsd mice was characterized using chronic fluoxetine as a reference compound. Additional tests were included to support the interpretation of results and exclude confounding pharmacological effects. Behaviors in vehicle-treated mice were furthermore analyzed for relatedness to deepen the understanding of parameters measured. We found that exploitation of the previously rewarded image was independent of exploration and acquisition of the new reward contingency and could be differentially modulated by fluoxetine, supporting recent theories that these processes are not mutually exclusive. Specifically, fluoxetine reduced mistake rate, premature and perseverative responses, and promoted conservative strategies during reversal without affecting hit rate. These effects appeared to be most prominent during the late stage of reversal learning, where accuracy was above chance level. Analysis of behaviors in vehicle-treated mice suggested that exploitation was related to an impulsive-like deficit in response inhibition, while exploration was more related to motivation. This new schedule was feasible, easy to implement, and can provide a deeper understanding of the cognitive sub-processes during reversal.

Several studies over the past two decades have investigated the neuropsychological deficits in children with attention deficit hyperactivity disorder (ADHD), but much less has been done on adults. This study aimed to assess the deficits in executive functions of adults with ADHD, especially in the areas of attention, inhibition, impulsivity, and planning. Twenty-four adults (18 years and older) diagnosed with ADHD according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria, and also assessed with Conners' Adult ADHD Rating Scale, participated in the study. Executive functions in cases were compared with 20 matched controls through the three instruments of Tower of London (TOL), Continuous Performance Test (CPT), and Stroop test. Performance of cases was weaker than that of the control group in TOL. The difference was significant in subsequent thinking time in most of the trials and number of movements only at level 2. In CPT, the adults with ADHD made more commission errors. In addition, the ADHD cases made more errors in the word card of the Stroop test, and the time they spent reading all three cards was significantly longer than that of the control group. Our study suggests that several deficits in executive functions related to ADHD persist into adulthood, such as impairments in planning time and set shifting, response inhibition, impulsivity, and visuolingual processing. However, simple (visual-motor processing) and sustained attention might improve with age.