Impaired Cognitive Flexibility Research Articles

Impaired cognitive flexibility in schizophrenia: A systematic review of behavioral and neurobiological findings

Background and hypothesisImpaired 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. MethodsTwo 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. Results38 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. ConclusionIncluded 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.

Rhynchophylline Alleviates Hyperactivity and Cognitive Flexibility Impairment Associated With Inhibition of Inflammatory Responses in Mice That Partly Lack the Dopamine Transporter Protein.

Rhynchophylline (RHY) can alleviate some cognitive flexibility impairment and stereotyped behavior for attention-deficit hyperactivity disorder (ADHD) and Tourette syndrome (TS) patients as one of a keyextract and an active ingredient in Ningdong granule (NDG), which is a Traditional Chinese medicine (TCM) preparation widely used in the treatment of ADHD and TS children in China; however, the underlying mechanism is not well understood. Therefore, this study aimed to evaluate how RHY alleviates hyperactivity and cognitive flexibility impairment while inhibiting inflammatory responses in mice that partly lack dopamine transporter protein (DAT- mice). Male DAT- mice were randomly divided into the RHY group (n = 8) and administered RHY (30mg/kg) in the DAT- group (n = 8) and administered saline (i.p., 10mL/kg) in wild-type (WT) mice as the WT control group (n = 8). Hyperactivity and cognitive flexibility impairment were evaluated by the open field test (OFT) and the Morris water maze (MWM) test. The levels of the inflammatory factors of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in cortical homogenates were tested by enzyme-linked immunosorbent assays (ELISA) after 8 weeks of treatment with RHY. In vitro, primary microglia and astrocytes extracted from the cortices of DAT- neonatal mice and WT neonatal mice were treated with lipopolysaccharide (LPS) (1mg/mL) to induce neuroinflammatory responses and with RHY (20mM) for 48h. The levels of the inflammatory factors TNF-α, IL-1β, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX2) in the culture medium were measured at 6h, 24h, and 48h after treatment with LPS and RHY. RHY ameliorated hyperactivity and cognitive flexibility impairment in DAT- mice and inhibited the expression of the inflammatory factors TNF-α, IL-1β, iNOS, and COX-2 in microglia and astrocytes in vitro, and also inhibited the expression of TNF-α and IL-1β in cortical homogenates after 8 weeks of treatment. RHY improved hyperactivity and cognitive flexibility impairment through inhibiting inflammatory responses in DAT- mice.

Conceptualization and standardization of a non-invasive closed head injury model using directed shockwave to mice

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide, with closed head injury (CHI) being one of the most common forms of TBI. Preclinical modeling of TBI is challenging due to confounding factors like craniectomy and poorly controlled injury severity. This study proposes a non-invasive CHI model using directed shockwaves. The mice heads were exposed to the shockwave and accommodated together following the implantation of RFID tags for automated neurocognitive assessment. Following a 13-day paradigm, mice underwent a digital gait analysis and subsequent classical behavioral test paradigms for affective, cognitive, and locomotor functions. Qualitative and quantitative histopathological assessment was carried out for shockwave pulses-dependent changes in terms of lesion volume, neuronal death, dendritic complexity, and spine density. Studies showed shockwave pulses-dependent differences in survivability, righting reflex, neural damage, and death. Shockwave-exposed mice showed significantly impaired learning and cognitive flexibility. Interestingly, exposed mice showed locomotor hyperactivity and risk-taking behavior (lack of anxiety) along with depression-like phenotypes. Our result suggests that the shockwave-based CHI models result in the clinically relevant phenotype and are precisely controlled for reproducibility.

Witnessing their mother’s acute and prolonged stress affects executive functioning in children

Stress can detrimentally affect physical and mental health, especially during childhood. During this critical period, parental bonds can foster resilience or amplify stress. This study explored whether mothers’ everyday stress can act as a source of childhood stress, affecting children’s executive functioning. 76 healthy mother-child dyads participated, with mothers assigned to a stress-inducing or stress-free condition. Children observed their mothers and were subsequently tested for cognitive flexibility and working memory. Subjective stress, heart rate, and cortisol were measured repeatedly in mothers and children, alongside everyday stress perceptions. Linear mixed models showed that children’s acute stress response was associated with impaired cognitive flexibility. Maternal stress, both acute and past-month, was a better predictor of children’s cognitive performance than children’s own stress. Quadratic relationships indicated the highest error rates at very low and high maternal stress. We found no evidence that children’s working memory was impaired by their own or their mothers’ stress. Although expected covariations of acute or prolonged stress between mothers and children were not observed, an interaction between maternal past-month stress and acute stress condition provided insights into adaptive mechanisms in children. These findings underscore the significant impact of maternal stress on children’s executive functioning, illustrating how parental experiences shape children’s everyday outcomes.

Prophylactic clemastine treatment improves influenza A virus-induced cognitive dysfunction in mice

Respiratory infection by influenza A virus (IAV) is known to cause systemic inflammation, neuroinflammation, and cognitive impairment. We previously found that experimental infection with IAV affected oligodendrocyte homeostasis, which was associated with altered expression of genes involved in myelin maintenance as well as the lipidome. In this study, we sought to determine if clemastine, an antihistamine with myelin promoting properties, could reverse the effects of IAV on oligodendrocyte (OL) specific genes, as well as mitigate infection-induced cognitive impairment. Male and female C57BL/6J mice were randomized into experimental groups based on clemastine treatment, infection, and sex. Treatment with vehicle or clemastine (10 mg/kg/d) commenced seven days prior to inoculation with either saline or IAV and continued throughout the experiment. Body weight was measured throughout the infection. Spatial learning and memory were assessed by Morris water maze. Sickness behavior was assessed by measuring burrowing response. Immune cell responses were determined by flow cytometry, RT-qPCR, antigen recall assays and ELISA, and viral load assessed by RT-qPCR. Hippocampal levels of neuroinflammatory (Tnf, Cdkn1a) and myelin (Plp1, Mag, Ugt8a) genes were determined by RT-qPCR. Mice infected with IAV developed weight loss, impaired cognitive flexibility, reduced burrowing behavior, altered lung immune cell infiltration, increased circulating anti-viral IgM and IgG levels and increased T cell responses to IAV epitopes. Infection increased hippocampal levels of genes associated with neuroinflammation and decreased levels of genes involved in myelination. Clemastine treatment resulted in earlier recovery of weight loss in males and increased IgM levels for both sexes, but neither affected expression levels of Tnf or Cdkn1a, nor rescued changes to oligodendrocyte genes. However, treatment mitigated infection-induced neurocognitive impairment.

The Orbitofrontal Cortex to Striatal Cholinergic Interneuron Circuit Controls Cognitive Flexibility Shaping Alcohol-Seeking Behavior

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. Mice were trained on two-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. 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 pre-inhibition mechanism. Importantly, remodeling the OFC-DMS circuit by inducing LTP 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 D2 receptor-expressing medium spiny neurons (D2-MSNs) but not in D1-MSNs. Finally, activation of the OFC-CIN-D2-MSN circuit decreased alcohol-seeking behavior. Improving OFC-CIN circuit-mediated cognitive flexibility may provide a novel strategy for treating uncontrolled alcohol-seeking behavior.

Sleep restriction and age effects on distinct aspects of cognition in adolescents.

Insufficient sleep negatively impacts scholastic performance in children and adolescents. Here we use a dose response time in bed (TIB) restriction study to evaluate associations between sleep loss and multiple aspects of cognition. We evaluated changes in cognitive measures across ages 10 to 23 years and determined whether the effects of sleep loss changed across this age range. A younger cohort (n=77, age range 9.9 to 16.2 years) was studied annually for 3 years. An older cohort study (n=82, age range 15 to 22.8 years) was interrupted by the COVID pandemic with 25 participants completing multiple years. Annually participants completed each of three TIB conditions: four consecutive nights with 7, 8.5, or 10h in bed. A day of cognitive testing followed the fourth night. Restricting TIB to 7h was associated with impaired top-down attentional control and cognitive flexibility, but performance did not differ between the 8.5 and 10h TIB conditions. Psychomotor vigilance test performance decreased as TIB was restricted from 10 to 8.5h and decreased further with restriction to 7h. Sternberg test measures of working memory were not significantly affected by TIB restriction. The effects of sleep loss on these cognitive measures did not change significantly with age, but age-related improvement in many of the measures may compensate for some sleep loss effects. The findings here do not indicate an adolescent decrease in sleep need; however, the minimal duration of sleep needed for optimal performance appears to differ depending on the cognitive measure.

Effects of chronic social defeat stress on social behavior and cognitive flexibility for early and late adolescent

This study investigated the risk to social behavior and cognitive flexibility induced by chronic social defeat stress (CSDS) during early and late adolescence (EA and LA). Utilizing the “resident-intruder” stress paradigm, adolescent male Sprague-Dawley rats were exposed to CSDS during either EA (postnatal days 29–38) or LA (postnatal days 39–48) to explore how social defeat at different stages of adolescence affects behavioral and cognitive symptoms commonly associated with psychiatric disorders. After stress exposure, the rats were assessed for anxiety-like behavior in the elevated plus maze, social interaction, and cognitive flexibility through set-shifting and reversal-learning tasks under immediate and delayed reward conditions. The results showed that CSDS during EA, but not LA, led to impaired cognitive flexibility in adulthood, as evidenced by increased perseverative and regressive errors in the set-shifting and reversal-learning tasks, particularly under the delayed reward condition. This suggests that the timing of stress exposure during development has a significant impact on the long-term consequences for behavioral and cognitive function. The findings highlight the vulnerability of the prefrontal cortex, which undergoes critical maturation during early adolescence, to the effects of social stress. Overall, this study demonstrates that the timing of social stressors during adolescence can differentially shape the developmental trajectory of cognitive flexibility, with important implications for understanding the link between childhood/adolescent adversity and the emergence of psychiatric disorders.

Poly (I:C)-induced maternal immune activation generates impairment of reversal learning performance in offspring.

Maternal immune activation (MIA) induces a variety of behavioral and brain abnormalities in offspring of rodent models, compatible with neurodevelopmental disorders, such as schizophrenia or autism. However, it remains controversial whether MIA impairs reversal learning, a basic expression of cognitive flexibility that seems to be altered in schizophrenia. In the present study, MIA was induced by administration of a single dose of polyriboinosinic-polyribocytidylic acid (Poly (I:C) (5 mg/kg i.p.)) or saline to mouse pregnant dams in gestational day (GD) 9.5. Immune activation was monitored through changes in weight and temperature. The offspring were evaluated when they reached adulthood (8 weeks) using a touchscreen-based system to investigate the effects of Poly (I:C) on discrimination and reversal learning performance. After an initial pre-training, mice were trained to discriminate between two different stimuli, of which only one was rewarded (acquisition phase). When the correct response reached above 80% values for two consecutive days, the images were reversed (reversal phase) to assess the adaptation capacity to a changing environment. Maternal Poly (I:C) treatment did not interfere with the learning process but induced deficits in reversal learning compared to control saline animals. Thus, the accuracy in the reversal phase was lower, and Poly (I:C) animals required more sessions to complete it, suggesting impairments in cognitive flexibility. This study advances the knowledge of how MIA affects behavior, especially cognitive domains that are impaired in schizophrenia. The findings support the validity of the Poly (I:C)-based MIA model as a tool to develop pharmacological treatments targeting cognitive deficits associated with neurodevelopmental disorders.

Impaired cognitive flexibility in major depressive disorder: Evidences from spatial-temporal ERPs analysis

BackgroundMajor Depressive Disorder (MDD) may exhibit impairments in cognitive flexibility. This study investigated whether the cognitive flexibility deficits in MDD are evident across general stimuli or specific to emotional stimuli, while exploring the underlying neuropsychological mechanism. MethodsA total of 41 MDD patients and 42 healthy controls (HCs) were recruited. Event-related potentials (ERPs) were recorded when participants performed a non-emotional and an emotional task switching paradigm (N-ETSP and ETSP), both of which assessed cognitive flexibility. Microstate and source localization analysis were applied to reflect brain activity among different brain areas during task switching. ResultsIn the N-ETSP, MDD group showed larger P3 difference wave (Pd3) amplitudes and longer P2 difference wave (Pd2) latencies. In the ETSP, MDD group displayed smaller N2 difference wave (Nd2) amplitudes and larger Pd3 amplitudes. The comparison of sLORETA images of emotional switch task and emotional repeat task showed that MDD group had increased activation in the precentral gyrus in microstate2 of the P2 time window and had reduced activation in the middle occipital gyrus in microstate3 of the N2 time window. LimitationsThe cross-sectional design failed to capture dynamic changes in cognitive flexibility in MDD. ConclusionsMDD demonstrated impaired cognitive flexibility respond to both non-emotional and emotional stimuli, with greater impairment for negative emotional stimuli. These deficits are evident in abnormal ERPs component during the early attention stage and the later task preparation stage. Furthermore, abnormal emotional switching cost in MDD appears to be related to early abnormal perceptual control in the parietal-occipital cortex.

The Aggregation of α-Synuclein in the Dorsomedial Striatum Significantly Impairs Cognitive Flexibility in Parkinson's Disease Mice.

This study focused on α-synuclein (α-syn) aggregation in the dorsomedial striatum (DMS) so as to investigate its role in the cognitive flexibility of Parkinson's disease (PD). Here, we investigated the cognitive flexibility by assessing reversal learning abilities in MPTP-induced subacute PD model mice and in C57BL/6J mice with α-syn aggregation in the DMS induced by adenovirus (AAV-SNCA) injection, followed by an analysis of the target protein's expression and distribution. PD mice exhibited impairments in reversal learning, positively correlated with the expression of phosphorylated α-syn in the DMS. Furthermore, the mice in the AAV-SNCA group exhibited reversal learning deficits and a reduction in acetylcholine levels, accompanied by protein alterations within the DMS. Notably, the administration of a muscarinic receptor 1 (M1R) agonist was able to alleviate the aforementioned phenomenon. These findings suggest that the impaired cognitive flexibility in PD may be attributed to the diminished activation of acetylcholine to M1R caused by α-syn aggregation.

Cognitive Alterations Associated with Remission and Alcohol Dependence Severity in Ethnically Diverse Patients of Siberia.

Impaired cognition in individuals with alcohol dependence may be associated with increased relapse risk. It has been recorded in more than half of patients during six months after treatment. In certain ethnic groups, for example, Tuvinians, the indigenous people of Siberia, relapses occur in extremely short periods of one to three months after treatment. An approach currently used to alcohol dependence treatment may be less effective for these patients. The study aimed to investigate cognitive sequelae in indigenous Tuvinian patients with alcohol dependence. The sample included 166 patients, 74 of indigenous ethnicity (Tuvinians) and 92 non-indigenous white patients. Data on inhibitory control, cognitive flexibility, attention, and working memory were collected from all the patients and processed using cluster analysis. The clustering data were then complemented by indicators of disorder dynamics, impulsivity, and emotion regulation. The clustering procedure revealed groups with severe cognitive sequelae. More than four-fold attention decrease was found in 43.5% of non-indigenous patients, and more impaired cognitive flexibility was revealed among 60.8% of indigenous patients. Groups with severe cognitive sequelae had higher impulsivity, maladaptive emotion regulation, more hospitalizations, faster disease progression, and shorter remissions. The latter was significantly reduced to 90 days on average in the severe group of indigenous patients versus 135 days of remission in the non-indigenous severe group. Results obtained may advance tailored intervention in alcohol-dependent patients of the indigenous Tuvinian ethnicity. While little is still known about the alcohol dependence course and consequences in the indigenous Tuvinians of Siberia, this study contributes to the global mental health data on alcohol abuse and dependence in indigenous communities.

Probing cognitive flexibility in Shank2-deficient mice: Effects of D-cycloserine and NMDAR signaling hub dynamics

Neurodevelopmental disorders such as autism spectrum disorder (ASD) have a heterogeneous etiology but are largely associated with genetic factors. Robust evidence from recent human genetic studies has linked mutations in the Shank2 gene to idiopathic ASD. Modeling these Shank2 mutations in animal models recapitulates behavioral changes, e.g. impaired social interaction and repetitive behavior of ASD patients. Shank2-deficient mice exhibit NMDA receptor (NMDAR) hypofunction and associated behavioral deficits. Of note, NMDARs are strongly implicated in cognitive flexibility. Their hypofunction, e.g. observed in schizophrenia, or their pharmacological inhibition leads to impaired cognitive flexibility. However, the association between Shank2 mutations and cognitive flexibility is poorly understood. Using Shank2-deficient mice, we explored the role of Shank2 in cognitive flexibility measured by the attentional set shifting task (ASST) and whether ASST performance in Shank2-deficient mice can be modulated by treatment with the partial NMDAR agonist D-cycloserine (DCS). Furthermore, we investigated the effects of Shank2 deficiency, ASST training, and DCS treatment on the expression level of NMDAR signaling hub components in the orbitofrontal cortex (OFC), including NMDAR subunits (GluN2A, GluN2B, GluN2C), phosphoglycerate dehydrogenase and serine racemase. Surprisingly, Shank2 deficiency did not affect ASST performance or alter the expression of the investigated NMDAR signaling hub components. Importantly, however, DCS significantly improved ASST performance, demonstrating that positive NMDAR modulation facilitates cognitive flexibility. Furthermore, DCS increased the expression of GluN2A in the OFC, but not that of other NMDAR signaling hub components. Our findings highlight the potential of DCS as a pharmacological intervention to improve cognitive flexibility impairments downstream of NMDAR modulation and substantiate the key role of NMDAR in cognitive flexibility.

Peripuberty Is a Sensitive Period for Prefrontal Parvalbumin Interneuron Activity to Impact Adult Cognitive Flexibility.

Developmental windows in which experiences can elicit long-lasting effects on brain circuitry and behavior are called "sensitive periods" and reflect a state of heightened plasticity. The classic example of a sensitive period comes from studies of sensory systems, like the visual system, where early visual experience is required for normal wiring of primary visual cortex and proper visual functioning. At a mechanistic level, loss of incoming visual input results in a decrease in activity in thalamocortical neurons representing the affected eye, resulting in an activity-dependent reduction in the representation of those inputs in the visual cortex and loss of visual perception in that eye. While associative cortical regions like the medial prefrontal cortex (mPFC) do not receive direct sensory input, recent findings demonstrate that changes in activity levels experienced by this region during defined windows in early development may also result in long-lasting changes in prefrontal cortical circuitry, network function, and behavior. For example, we recently demonstrated that decreasing the activity of mPFC parvalbumin-expressing (PV) interneurons during a period of time encompassing peripuberty (postnatal day P14) to adolescence (P50) led to a long-lasting decrease in their functional inhibition of pyramidal cells, as well as impairments in cognitive flexibility. While the effects of manipulating mPFC PV interneuron activity were selective to development, and not adulthood, the exact timing of the sensitive period for this manipulation remains unknown. To refine the sensitive period in which inhibiting mPFC PV cell activity can lead to persistent effects on prefrontal functioning, we used a chemogenetic approach to restrict our inhibition of mPFC PV activity to two distinct windows: (1) peripuberty (P14-P32) and (2) early adolescence (P33-P50). We then investigated adult behavior after P90. In parallel, we performed histological analysis of molecular markers associated with sensitive period onset and offset in visual cortex, to define the onset and offset of peak-sensitive period plasticity in the mPFC. We found that inhibition of mPFC PV interneurons in peripuberty (P14-P32), but not adolescence (P33-P50), led to an impairment in set-shifting behavior in adulthood manifest as an increase in trials to reach criterion performance and errors. Consistent with a pubertal onset of sensitive period plasticity in the PFC, we found that histological markers of sensitive period onset and offset also demarcated P14 and P35, respectively. The time course of expression of these markers was similar in visual cortex. Both lines of research converge on the peripubertal period (P14-P32) as one of heightened sensitive period plasticity in the mPFC. Further, our direct comparison of markers of sensitive period plasticity across the prefrontal and visual cortex suggests a similar time course of expression, challenging the notion that sensitive periods occur hierarchically. Together, these findings extend our knowledge about the nature and timing of sensitive period plasticity in the developing mPFC.

Disentangling cognitive flexibility: a model-based assessment of women with anorexia nervosa

ABSTRACT Cognitive flexibility (CF) has been proposed as a potential trait marker in anorexia nervosa (AN), although findings have been inconsistent. To address this inconsistency, we applied a model that distinguishes between three subtypes of CF: task switching, switching sets, and stimulus-response mapping, which we then assessed using a paradigm-based task battery. The aim of the study was to investigate how AN is associated with these three CF subtypes. Thirty-three women with AN and 37 age- and education-matched controls performed a battery of computerized cognitive tasks to assess the three CF subtypes. Compared to the control group, individuals with AN exhibited poorer performance on the task switching and switching sets subtypes, as measured by response time switch cost, but not on the stimulus-response mapping subtype. No differences were found between the groups in response accuracy. Furthermore, switching sets as compared to the task switching and stimulus-response mapping subtypes was found to better explain the differences between the groups. These findings indicate a domain-specific impairment in CF among patients with AN, reflecting deficits observed in subtypes related to the disorder’s characteristics, particularly that associated with visual perception. Therefore, CF impairment in AN should not be viewed dichotomously, but rather as a relative impairment that varies depending on the specific CF subtype.

Executive function performance in children and adolescent patients with narcolepsy type 1

ObjectiveThe executive function profile in patients with narcolepsy type 1 (NT1) has been mentioned; however, limited research exists on children and adolescent patients with NT1.This study aims to assess executive function in children and adolescent patients with NT1 in China, examine potential influencing factors and evaluate the short-term treatment effect on executive function. Methods53 NT1 patients (36 males, age 12.2 ± 3.4 years) and 37 healthy controls (23 males, age 12.2 ± 2.5 years) underwent self-reported measures assessing subjective sleepiness, depression, anxiety and sleep quality. A comprehensive neuropsychological test was administered to assess executive function domains, including processing speed, inhibitory control, cognitive flexibility and working memory. These assessments were repeated in NT1 patients after three-day regular drug treatment. ResultsNT1 patients exhibited higher levels of excessive daytime sleepiness, depression, anxiety, and poor sleep quality compared to healthy controls. Patients showed impaired processing speed, inhibitory control and cognitive flexibility (p < 0.05), whereas working memory was unaffected (p > 0.05). Regression analysis revealed that parameters from sleep monitoring, such as sleep efficiency and sleep latency, were correlated with executive function performance after controlling for age, gender, and education years. The short-term treatment led to improvements in inhibitory control, cognitive flexibility, and working memory. ConclusionThe findings showed that executive function was impaired among children and adolescent patients with NT1, which was associated with objective sleep parameters. Furthermore, this study emphasizes the necessity of neuropsychological assessments and early interventions among children and adolescent NT1 patients.

Neurocognitive functioning in adults with trichotillomania: Predictors of treatment response and symptom severity in a randomized control trial

Trichotillomania (TTM) is associated with impairments in response inhibition and cognitive flexibility, but it is unclear how such impairments relate to treatment outcome. The present study examined pre-treatment response inhibition and cognitive flexibility as predictors of treatment outcome, change in these domains from pre-to post-treatment, and associations with TTM severity. Participants were drawn from a randomized controlled trial comparing acceptance-enhanced behavior therapy (AEBT) to psychoeducation and supportive therapy (PST) for TTM. Adults completed assessments at pre-treatment (n = 88) and following 12 weeks of treatment (n = 68). Response inhibition and cognitive flexibility were assessed using the Stop Signal Task and Object Alternation Task, respectively. Participants completed the MGH-Hairpulling Scale. Independent evaluators administered the NIMH-Trichotillomania Severity Scale and Clinical Global Impressions-Improvement Scale. Higher pre-treatment TTM severity was associated with poorer pre-treatment cognitive flexibility, but not response inhibition. Better pre-treatment response inhibition performance predicted positive treatment response and lower post-treatment TTM symptom severity, irrespective of treatment assignment. Cognitive flexibility did not predict treatment response. After controlling for age, neither neurocognitive variable changed during treatment. Response inhibition and cognitive flexibility appear uniquely related to hair pulling severity and treatment response in adults with TTM. Implications for treatment delivery and development are discussed.

Systemic inflammation in Aβ1-40-induced Alzheimer’s disease model: New translational opportunities

Alzheimer disease (AD) is the most frequent cause of dementia, and the most common neurodegenerative disease, which is characterized by memory impairment, neuronal death, and synaptic loss in the hippocampus. Sporadic late-onset AD, which accounts for over 95 % of disease cases, is a multifactorial pathology with complex etiology and pathogenesis. Nowadays, neuroinflammation is considered the third most important component of AD pathogenesis in addition to amyloid peptide generation and deposition. Neuroinflammation is associated with the impairment of blood–brain barrier and leakage of inflammatory mediators into the periphery with developing systemic inflammatory responses. Systemic inflammation is currently considered one of the therapeutic targets for AD treatment, that necessitates in-depth study of this phenomenon in appropriate non-transgenic animal models. This study was aimed to explore systemic inflammatory manifestations in rats with Aβ1-40-induced AD. The impairment of spatial memory and cognitive flexibility in Aβ1-40-lesioned rats was accompanied by pronounced systemic inflammation, which was confirmed by commonly accepted biomarkers: increased hematological indices of systemic inflammation (NLR, dNLR, LMR, PLR and SII), signs of anemia of inflammation or chronic diseases, and pro-inflammatory polarized activation of circulating phagocytes. In addition, markers of systemic inflammation strongly correlated with disorders of remote cognitive flexibility in Aβ1-40-lesioned rats. These results indicate, that Aβ1-40-induced AD model permits the investigation of specific element of the disease – systemic inflammation in addition to well reproduced neuroinflammation and impairment of spatial memory and cognitive flexibility. It increases translational value of this well-known model.

A shift to a standard diet after exposure to a high-fat, high-sucrose diet from gestation to weaning restores brain metabolism and behavioral flexibility in adult rats

Prolonged consumption of diets high in saturated fat and sugar has been related to obesity and overweight, which in turn are linked to cognitive impairment in both humans and rodents. This has become a current issue, especially in children and adolescents, because these stages are crucial to neurodevelopmental processes and programming of adult behavior. To evaluate the effects of gestational and early exposure to an obesogenic diet, three groups with different dietary patterns were established: high-fat and high-sucrose diet (HFS), standard diet (SD), and a dietary shift from a high-fat, high-sucrose diet to a standard diet after weaning (R). Spatial learning and behavioral flexibility in adult male and female Wistar rats were evaluated using the Morris water maze (MWM) at PND 60. Furthermore, regional brain oxidative metabolism was assessed in the prefrontal cortex and the hippocampus. Contrary to our hypothesis, the HFS diet groups showed similar performance on the spatial learning task as the other groups, although they showed impaired cognitive flexibility. The HFS group had increased brain metabolic capacity compared to that of animals fed the standard diet. Shifting from the HFS diet to the SD diet after weaning restored the brain metabolic capacity in both sexes to levels similar to those observed in animals fed the SD diet. In addition, animals in the R group performed similarly to those fed the SD diet in the Morris water maze in both tasks. However, dietary shift from HFS diet to standard diet after weaning had only moderate sex-dependent effects on body weight and fat distribution. In conclusion, switching from an HFS diet to a balanced diet after weaning would have beneficial effects on behavioral flexibility and brain metabolism, without significant sex differences.

The capacity of cognitive tests to detect generalized anxiety disorder (GAD): A pilot study

Cognitive impairment remains understudied in generalized anxiety disorder (GAD), despite the high prevalence and substantial burden associated with this disorder. We aimed to assess cognitive impairment in patients with GAD and evaluate the ability of cognitive tests to detect this disorder. Because of its high rate of comorbidity, we also examined how other anxiety disorders and current major depressive episodes affected our results. We tested 263 consecutive general practice outpatients. We used the GAD-7 and the Mini International Neuropsychiatric Interview (MINI) to detect anxiety and mood disorders. We assessed cognitive performance with the Stroop test, a facial emotion recognition test, and the trail-making test (TMT). Compared to patients without GAD, patients with GAD were significantly slower to complete the TMT(B-A) and faster to recognize emotions, especially negative ones such as disgust and anger. When controlling for other anxiety disorders and current major depressive episode, GAD retained a significant effect on the TMT(B-A), but not on the emotion recognition test. The TMT(B-A) could detect GAD with good accuracy (area under the curve (AUC) = 0.83, maximal Youden's index = 0.56), which was by no means comparable to the GAD-7 (AUC = 0.97, Youden's index = 0.81). While it is not efficient enough to replace the GAD-7 as a diagnostic tool, the capacity of the TMT(B-A) to detect GAD emphasizes the importance of cognitive flexibility impairment in GAD.