Impaired Executive Function Research Articles

A Comparison between the Effectiveness of computerized Cognitive Rehabilitation Training and transcranial Direct Current Stimulation on Dialysis Patients' Executive Functions.

Executive function impairments are among the most common dialysis side effects. The present study aims to compare the efficiency of transcranial Direct Current Stimulation (tDCS) with computerized Cognitive Rehabilitation Training (cCRT) on dialysis patients' executive functions. The present study, a quasi-experimental effort, adopted a pre-test/post-test method that included a control (sham) group. The study sample consisted of 30 participants, selected through the convenience sampling method, and categorized into three groups of cCRT, tDCS, and sham participants. The cCRT participants were asked to complete 8 tasks in Captain's Log MindPower Builder software. The tDCS participants were treated with a 0.06 mA/cm2 current with the anodal electrode on F3 and the cathodal electrode on Fp2. For the sham participants, the electrodes were put on the same regions but there was no current stimulation. The treatment lasted for 10 sessions carried out every other day. The results of MANCOVA showed no significant difference between the sham group and the cCRT group in any of the executive function items. . However, between the sham group and the tDCS group was detected a significant difference in spatial working memory (p \< 0.05) and a marginally significant in cognitive flexibility (p = 0.091). No significant difference was reported between cCRT and tDCS groups in any item. According to the findings of the study, given the efficacy of tDCS on spatial working memory and cognitive flexibility for dialysis patients, it can be used to improve these skills.

Investigation of Siblings of Patients Diagnosed with Substance-Induced Psychotic Disorder in terms of Cognitive Functions and Clinical High-Risk State for Psychosis

Objective: This study aimed to investigate the influence of familial predisposition on substance-induced psychosis among healthy siblings of patients diagnosed with substance-induced psychotic disorder, who themselves lack any family history of psychotic disorders. Additionally, the study aimed to explore clinical high-risk states for psychosis, schizotypal features, and neurocognitive functions in comparison to a healthy control group. Method: The study compared healthy siblings of 41 patients diagnosed with substance-induced psychotic disorder with 41 healthy volunteers without a family history of psychotic disorders, matching age, gender, and education. Sociodemographic and clinical characteristics of participants were obtained using data collection forms. The Comprehensive Assessment of At-Risk Mental States (CAARMS) and the Structured Interview for Schizotypy-Revised Form (SIS-R) scales were utilized to assess clinical high risk for psychosis. Neurocognitive functions were evaluated with digit span test (DST), trail making test part A-B (TMT), verbal fluency test (VFT), and Stroop test (ST). Results: Analysis using the CAARMS scale revealed that 39% of siblings and 7.3% of the control group were at clinically high risk for psychosis, indicating a significant difference in rates of psychotic vulnerability. Comparison between siblings and the control group showed significant differences in mean SIS-R subscale scores, including social behavior, hypersensitivity, referential thinking, suspiciousness, illusions, and overall oddness, as well as in mean neurocognitive function scores, including errors in TMT-A, TMT-B, and VFT out-of-category errors, with siblings exhibiting poorer performance. Conclusion: Our study suggests that healthy siblings of patients with substance-induced psychosis exhibit more schizotypal features and have a higher risk of developing psychosis compared to healthy controls. Additionally, siblings demonstrate greater impairment in attention, response inhibition, and executive functions compared to healthy controls, indicating the potential role of genetic predisposition in the development of substance-induced psychotic disorder.

Cage effects on synaptic plasticity and its modulation in a mouse model of fragile X syndrome.

Fragile X syndrome (FXS) is characterized by impairments in executive function including different types of learning and memory. Long-term potentiation (LTP), thought to underlie the formation of memories, has been studied in the Fmr1 mouse model of FXS. However, there have been many discrepancies in the literature with inconsistent use of littermate and non-littermate Fmr1 knockout (KO) and wild-type (WT) control mice. Here, the influence of the breeding strategy (cage effect) on short-term potentiation (STP), LTP, contextual fear conditioning (CFC), expression of N-methyl-d-aspartate receptor (NMDAR) subunits and the modulation of NMDARs, were examined. The largest deficits in STP, LTP and CFC were found in KO mice compared with non-littermate WT. However, the expression of NMDAR subunits was unchanged in this comparison. Rather, NMDAR subunit (GluN1, 2A, 2B) expression was sensitive to the cage effect, with decreased expression in both WT and KO littermates compared with non-littermates. Interestingly, an NMDAR-positive allosteric modulator, UBP714, was only effective in potentiating the induction of LTP in non-littermate KO mice and not the littermate KO mice. These results suggest that commonly studied phenotypes in Fmr1 KOs are sensitive to the cage effect and therefore the breeding strategy may contribute to discrepancies in the literature.This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.

In a circuit necessary for cognition and emotional affect, Alzheimer's-like pathology associates with neuroinflammation, cognitive and motivational deficits in the young adult TgF344-AD rat

In addition to extracellular amyloid plaques, intracellular neurofibrillary tau tangles, and inflammation, cognitive and emotional affect perturbations are characteristic of Alzheimer's disease (AD). The cognitive and emotional domains impaired by AD include several forms of decision making (such as intertemporal choice), blunted motivation (increased apathy), and impaired executive function (such as working memory and cognitive flexibility). However, the interaction between these domains of the mind and their supporting neurobiological substrates at prodromal stages of AD, or whether these interactions can be predictive of AD severity (individual variability), remain unclear. In this study, we employed a battery of cognitive and emotional tests in the young adult (5–7 mo) transgenic Fisher-344 AD (TgF344-AD; TgAD) rat model of AD. We also assessed whether markers of inflammation or AD-like pathology in the prelimbic cortex (PrL) of the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), or nucleus accumbens (NAc), all structures that directly support the aforementioned behaviors, were predictive of behavioral deficits. We found TgAD rats displayed maladaptive decision making, greater apathy, and impaired working memory that was indeed predicted by AD-like pathology in the relevant brain structures, even at an early age. Moreover, we report that the BLA is an early epicenter of inflammation, and notably, AD-like pathology in the PrL, BLA, and NAc was predictive of BLA inflammation. These results suggest that operant-based battery testing may be sensitive enough to determine pathology trajectories, including neuroinflammation, from early stages of AD.

Long-term outcomes of early exposure to repeated general anaesthesia in children with cystic fibrosis (CF-GAIN): a multicentre, open-label, randomised controlled phase 4 trial

Long-term effects of early, recurrent human exposure to general anaesthesia remain unknown. The Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) trial provided an opportunity to examine this issue in children randomly assigned in infancy to either repeated bronchoalveolar-lavage (BAL)-directed therapy with general anaesthesia or standard care with no planned lavages up to 5 years of age when all children received BAL-directed therapy under general anaesthesia. This multicentre, randomised, open-label phase 4 trial (CF-GAIN) used the original ACFBAL trial randomisation at 3·6 months (SD 1·6) to BAL-directed therapy or standard-care groups to assess the impact of general anaesthesia exposures over early childhood. Children who completed the ACFBAL trial, with a mean age of 5·1 (SD 0·18) years, received standardised neurobehavioural and health-related-quality-of-life assessment and brain MRI scans between Oct 8, 2013, and June 30, 2017, at a mean age of 12·8 (SD 1·7) years at three hospitals in Australia and one hospital in New Zealand. The primary outcome was a composite score of performance on a standardised, computer-based assessment of child attention, processing speed, and response inhibition skills (Conners Continuous Performance test, second edition). Secondary outcomes included intellectual function, other neurobehavioural measures, and brain imaging as an exploratory outcome. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN 12613000057785) and is completed. At 2 years, the BAL-directed therapy group (n=52) and standard-care group (n=45) had a median of 2·0 (IQR 1·0-3·0) and 0·0 (0·0-0·0) exposures, respectively. At completion of the ACFBAL trial, the BAL-directed therapy group had a median of 6·0 (4·0-9·5) exposures and the standard-care group 2·0 (1·0-4·0) exposures. At CF-GAIN completion, the BAL-directed therapy group had a median of 10·0 (IQR 6·5-14·5) exposures and the standard-care group 4·0 (3·0-7·0) exposures. Cumulative general anaesthesia exposure time was not prospectively collected but, for those with complete cumulative exposure time data to the end of the ACFBAL trial, the median cumulative exposure time for the BAL-directed therapy group (n=29) was 180 (IQR 140-285) min and for the standard-care group (n=32) was 48 (30-122) min. The mean Conners Continuous Performance test, second edition composite score was 51 (SD 8·1) in BAL-directed therapy group and 53 (8·8) in the standard-care group; difference -1·7 (95% CI -5·2 to 1·7; p=0·32) with similar performance on other neurobehavioural measures, including measures of executive function, intellectual quotient scores, and brain imaging. Our findings suggest that repeated general anaesthesia exposure in young children with cystic fibrosis is not related to functional impairment in attention, intellectual quotient, executive function, or brain structure compared with a group with fewer and shorter cumulative anaesthesia durations. National Health and Medical Research Council Australia, Queensland Government Health Service and Clinical Innovation Fellowship, and the Children's Hospital Foundation Queensland.

Rapidly progressive cognitive impairment resulting in heavy psychosocial burden in a patient with Fabry disease undergoing hemodialysis: a case report

BackgroundLong-term enzyme replacement therapy (ERT) may improve prognosis in the patients with Fabry disease (FD), however, detail psychosocial burden has not been focused on long life expectancy. We experienced a male case of FD under ERT, he was placed on hemodialysis and presented rapidly progressive cognitive function.Case presentationA 51-year-old male patient with FD has been receiving ERT from age of 38 years. Hemodialysis was initiated at the age of 47 years. The patient experienced several attacks of cerebral infarction, and brain images demonstrated wide-spread asymptomatic ischemic lesions. His behavior became problematic at the age of 51 years. He often exhibited restlessness during hemodialysis sessions and failure to communicate effectively. The patient experienced impairment of attention and executive function, topographical disorientation, and amnesia. Consequently, it was necessary for medical staff and family members to monitor his behavior for safe extracorporeal circulation and daily life activities. Annual standardized neuropsychiatric testing revealed worsening of cognitive performance.ConclusionsDespite treating with long-term ERT, it is necessary to determine the psychosocial burden derived from the progression of cognitive impairment in patients with FD undergoing hemodialysis.

Episodic memory network characteristics in patients with amnestic mild cognitive impairment accompanied by executive function impairment.

To explore the functional connectivity (FC) characteristics of the episodic memory network (EMN) in amnestic mild cognitive impairment (aMCI) patients with different levels of executive function (EF). This study included 76 participants from the Alzheimer's Disease Neuroimaging Initiative database, comprising 23 healthy controls (HCs) and 53 aMCI patients. Based on EF levels, aMCI patients were categorized into aMCI-highEF and aMCI-lowEF groups. Cognitive function scores, pathological markers (cerebrospinal fluid β-amyloid, total tau protein, phosphorylated tau protein, AV45-PET, and FDG-PET), and functional magnetic resonance imaging were collected and compared among the three groups. Seed-based FC analysis was used to examine differences in the EMN among the groups, and partial correlation analysis was employed to investigate the relationship between changes in FC and cognitive function scores as well as pathological markers. Compared to the aMCI-highEF group, the aMCI-lowEF group exhibited more severe cognitive impairment, decreased cerebral glucose metabolism, and elevated AV45 levels. Significant FC differences in the left superior temporal gyrus (STG) of the EMN were observed among the three groups. Post hoc analysis revealed that the aMCI-lowEF group had increased FC in the left STG compared to the HCs and aMCI-highEF groups, with statistically significant differences. Correlation analysis showed a significant negative correlation between the differences in FC in the left STG of aMCI-highEF and aMCI-lowEF groups and Rey Auditory Verbal Learning Test forgetting scores. Receiver operator characteristic curve analysis indicated an area under the curve of 0.741 for distinguishing between aMCI-highEF and aMCI-lowEF groups based on FC of left STG, with a sensitivity of 0.808 and a specificity of 0.667. aMCI-lowEF exhibits characteristic changes in FC within the EMN, providing theoretical support for the role of EF in mediating EMN alterations and, consequently, impacting episodic memory function.

Working memory performance predicts, but does not reduce, cocaine- and cannabinoid-seeking in adult male rats.

Cognitive deficits reflecting impaired executive function are commonly associated with psychiatric disorders, including substance use. Cognitive training is proposed to improve treatment outcomes for these disorders by promoting neuroplasticity within the prefrontal cortex, enhancing executive control, and mitigating cognitive decline due to drug use. Additionally, brain derived neurotrophic factor (BDNF) can facilitate plasticity in the prefrontal cortex and reduce drug-seeking behaviors. We investigated whether working memory training could elevate BDNF levels in the prefrontal cortex and if this training would predict or protect against cocaine or cannabinoid seeking. Adult male rats were trained to perform a 'simple' or 'complex' version of a delayed- match-to-sample working memory task. Rats then self-administered cocaine or the synthetic cannabinoid WIN55,212-2 and were tested for cued drug-seeking during abstinence. Tissue from the prefrontal cortex and dorsal hippocampus was analyzed for BDNF protein expression. Training on the working memory task enhanced endogenous BDNF protein levels in the prelimbic prefrontal cortex but not the dorsal hippocampus. Working memory training did not impact self-administration of either drug but predicted the extent of WIN self-administration and cocaine seeking during abstinence. These results suggest that working memory training promotes endogenous BDNF but does not alter drug-seeking or drug-taking behavior. However, individual differences in cognitive performance prior to drug exposure may predict vulnerability to future drug use.

The role of cognitive flexibility on higher level executive functions in mild cognitive impairment and healthy older adults

BackgroundMild Cognitive Impairment (MCI) is a preclinical condition between healthy and pathological aging, which is characterized by impairments in executive functions (EFs), including cognitive flexibility. According to Diamond’s model, cognitive flexibility is a core executive function, along with working memory and inhibition, but it requires the development of these last EFs to reach its full potential. In this model, planning and fluid intelligence are considered higher-level EFs. Given their central role in enabling individuals to adapt their daily life behavior efficiently, the goal is to gain valuable insight into the functionality of cognitive flexibility in a preclinical form of cognitive decline. This study aims to investigate the role of cognitive flexibility and its components, set-shifting and switching, in MCI. The hypotheses are as follows: (I) healthy participants are expected to perform better than those with MCI on cognitive flexibility and higher-level EFs tasks, taking into account the mediating role of global cognitive functioning; (II) cognitive flexibility can predict performance on higher-level EFs (i.e., planning and fluid intelligence) tasks differently in healthy individuals and those diagnosed with MCI.MethodsNinety participants were selected and divided into a healthy control group (N = 45; mean age 64.1 ± 6.80; 66.6% female) and an MCI group (N = 45; mean age 65.2 ± 8.14; 40% female). Cognitive flexibility, fluid intelligence, planning, and global cognitive functioning of all participants were assessed using standardized tasks.ResultsResults indicated that individuals with MCI showed greater impairment in global cognitive functioning and EFs performance. Furthermore, the study confirms the predictive role of cognitive flexibility for higher EFs in individuals with MCI and only partially in healthy older adults.

A 5-week Digital Intervention to Reduce Attention Problems in Children With ADHD: A Double-Blind Randomized Controlled Trial

Objective: Growing evidence suggests digital interventions may provide neurocognitive benefits for children with ADHD. This study aimed to investigate the efficacy of a digital attention intervention in children with ADHD. Method: In this double-blind randomized controlled trial 55 children with ADHD (5–9 years) were allocated to the intervention (N = 28) or control program (N = 27). Both programs were delivered via touchscreen tablets at home 5 days a week for 5 weeks. The primary outcome was change in the Test of Variables of Attention (TOVA) Attention Comparison Score (ACS) from pre- to post-intervention. Results: Participants who received the intervention had significantly greater improvements in the TOVA ACS from pre- to post-intervention than those in the control (p < .044). No intervention effects were observed on secondary outcomes assessing executive functioning, ADHD symptoms, or functional impairment. Conclusion: Collectively these findings provide insufficient evidence for the implementation of digital attention interventions for children with ADHD.

P.023 Review of imaging changes, cognitive decline, and dementia risk in cancer survivors after chemotherapy

Background: Cancer survival rates in Canada have been improving, leading to a steady increase in the number of survivors entering the typical ages of dementia onset. Yet, some cancer treatments (e.g. chemotherapy) are neurotoxic and adversely affect normal brain functioning. We conducted a review to examine changes observed in brain imaging and cognitive measures in survivorship, and long-term risk of dementia among cancer survivors. Methods: 91 Primary studies were selected from PubMed. Inclusion criteria were studies investigating the changes in brain imaging, cognition, and future dementia risk among adult survivors who received chemotherapy. Study quality was assessed based on 1) prospective, controlled design, 2) sample size, and 3) validated imaging and cognitive metrics. Results: Imaging studies identified MRI-based structural grey and white matter changes and functional network changes among survivors. Cognitive studies reported heterogeneous impairments in attention, memory, and executive function. In studies that examined dementia risk among cancer survivors, 67% reported lower risk of dementia, while 33% reported no association or a higher risk. Conclusions: While short-term cognitive impairment with associated changes on brain imaging is widely reported, findings concerning future or long-term cognitive impairment are mixed. Studies are warranted to identify potential connections between short-term and long-term cognitive function after cancer treatment.

Alterations in Blood-Brain Barrier Integrity and Lateral Ventricle Differ in Rats Exposed to Space Radiation and Social Isolation.

The proposed Mars missions will expose astronauts to long durations of social isolation (SI) and space radiation (SR). These stressors have been shown to alter the brain's macrostructure and microenvironment, including the blood-brain barrier (BBB). Breakdown of the BBB is linked to impaired executive functions and physical deficits, including sensorimotor and neurocognitive impairments. However, the precise mechanisms mediating these effects remain unknown. Additionally, the synergistic effects of combined exposure to SI and SR on the structural integrity of the BBB and brain remain unknown. We assessed the BBB integrity and morphology in the brains of male rats exposed to ground-based analogs of SI and SR. The rats exposed to SR had enlarged lateral ventricles and increased BBB damage associated with a loss of astrocytes and an increased number of leaky vessels. Many deficits observed in SR-treated animals were attenuated by dual exposure to SI (DFS). SI alone did not show BBB damage but did show differences in astrocyte morphology compared to the Controls. Thus, determining how single and combined inflight stressors modulate CNS structural integrity is crucial to fully understand the multiple pathways that could impact astronaut performance and health, including the alterations to the CNS structures and cell viability observed in this study.

Preoperative executive functioning impairments in patients with a meningioma: does a frontal location matter?

AbstractPatients with meningiomas frequently exhibit impairments in executive functioning. There are few studies specifically examining the role of frontal meningioma localization in executive functioning impairments. This study examines whether frontally located meningiomas are specifically associated with executive functioning impairments in a large sample of meningioma patients before treatment, using an axis-wise and lobe-based approach to meningioma localization. We retrospectively examined cognitive performances in 353 patients with frontal, frontally-involved and non-frontal meningiomas on a battery of tests including tests of executive functioning. We applied an axis-based approach to meningioma location, in addition to qualitative lobe-based localization. We examined the association between meningioma coordinates on an anterior-posterior axis and continuous cognitive performance scores in univariate correlations and linear regression analyses. We also examined the association between meningioma coordinates on an anterior-posterior axis with cognitive impairments in multivariable logistic regression analyses. Meningioma position on the anterior-posterior axis was only univariately associated with mean performance on the Stroop test Interference ratio and Symbol Digit Coding task. There was no (multivariable) association with impairments on tests of executive or non-executive domains. Increased odds of impairment on executive functioning tasks were associated with left-localization (Verbal Fluency) and larger meningioma volumes (Shifting Attention). We did not find a specific relation between a frontal meningioma location and executive functioning impairments, which may be explained by widespread organization of executive functioning throughout the brain, diffuse cognitive effects of the mass of meningiomas, functional reorganization due to neuroplasticity, or functional involvement of less-anteriorly located frontal areas.

Processing Speed Partially Mediates Executive Function Impairments in Adolescents with Congenital Heart Disease: Results from a Prospective Cohort Study

To assess processing speed, fine motor function, attention, and executive function (EF) impairments in adolescents with complex congenital heart disease (CHD) who underwent open-heart surgery during infancy. We administered a comprehensive neuropsychological test battery evaluating 5 EF domains: working memory, inhibition, cognitive flexibility, fluency, and planning and primary neurodevelopmental processes (PNPs): processing speed, fine motor function, and attention. The sample included 100 adolescents with complex CHD from a previous University Children's Hospital Zurich study, with 104 healthy controls for comparison. We generated scores for each EF domain and computed an EF summary score. Group comparisons and associations were analyzed with multiple regressions accounting for parental education. Mediation analysis explored how PNPs mediate the effect between a CHD diagnosis and EF. In adolescents with complex CHD, all EF domains and the EF summary score were impaired (β=0.20 to 0.37, all P<.05). Furthermore, they exhibited slower processing speed (β=0.27, P<.01) than healthy controls, with no differences in attention (β=-0.07, P=.34) and fine motor function (β=0.08, P=.34). Processing speed showed a strong association with the EF summary score (β=0.60, P<.001) and partially mediated the relationship between CHD diagnosis and the EF summary score (β=0.37, 95% CI [0.24, 0.50], P<.001). Adolescents with complex CHD show difficulties in EFs and processing speed. Notably, processing speed is strongly associated with EFs and partly accounts for EFs disparities between patients and healthy controls. Early detection and interventions for processing speed difficulties may improve EF outcomes in these patients.

Differentiating Prodromal Dementia with Lewy Bodies from Prodromal Alzheimer's Disease: A Pragmatic Review for Clinicians.

This pragmatic review synthesises the current understanding of prodromal dementia with Lewy bodies (pDLB) and prodromal Alzheimer's disease (pAD), including clinical presentations, neuropsychological profiles, neuropsychiatric symptoms, biomarkers, and indications for disease management. The core clinical features of dementia with Lewy bodies (DLB)-parkinsonism, complex visual hallucinations, cognitive fluctuations, and REM sleep behaviour disorder are common prodromal symptoms. Supportive clinical features of pDLB include severe neuroleptic sensitivity, as well as autonomic and neuropsychiatric symptoms. The neuropsychological profile in mild cognitive impairment attributable to Lewy body pathology (MCI-LB) tends to include impairment in visuospatial skills and executive functioning, distinguishing it from MCI due to AD, which typically presents with impairment in memory. pDLB may present with cognitive impairment, psychiatric symptoms, and/or recurrent episodes of delirium, indicating that it is not necessarily synonymous with MCI-LB. Imaging, fluid and other biomarkers may play a crucial role in differentiating pDLB from pAD. The current MCI-LB criteria recognise low dopamine transporter uptake using positron emission tomography or single photon emission computed tomography (SPECT), loss of REM atonia on polysomnography, and sympathetic cardiac denervation using meta-iodobenzylguanidine SPECT as indicative biomarkers with slowing of dominant frequency on EEG among others as supportive biomarkers. This review also highlights the emergence of fluid and skin-based biomarkers. There is little research evidence for the treatment of pDLB, but pharmacological and non-pharmacological treatments for DLB may be discussed with patients. Non-pharmacological interventions such as diet, exercise, and cognitive stimulation may provide benefit, while evaluation and management of contributing factors like medications and sleep disturbances are vital. There is a need to expand research across diverse patient populations to address existing disparities in clinical trial participation. In conclusion, an early and accurate diagnosis of pDLB or pAD presents an opportunity for tailored interventions, improved healthcare outcomes, and enhanced quality of life for patients and care partners.

Increased [18F]Fluorodeoxyglucose Uptake in the Left Pallidum in Military Veterans with Blast-Related Mild Traumatic Brain Injury: Potential as an Imaging Biomarker and Mediation with Executive Dysfunction and Cognitive Impairment.

Blast-related mild traumatic brain injury (blast-mTBI) can result in a spectrum of persistent symptoms leading to substantial functional impairment and reduced quality of life. Clinical evaluation and discernment from other conditions common to military service can be challenging and subject to patient recall bias and the limitations of available assessment measures. The need for objective biomarkers to facilitate accurate diagnosis, not just for symptom management and rehabilitation but for prognostication and disability compensation purposes is clear. Toward this end, we compared regional brain [18F]fluorodeoxyglucose-positron emission tomography ([18F]FDG-PET) intensity-scaled uptake measurements and motor, neuropsychological, and behavioral assessments in 79 combat Veterans with retrospectively recalled blast-mTBI with 41 control participants having no lifetime history of TBI. Using an agnostic and unbiased approach, we found significantly increased left pallidum [18F]FDG-uptake in Veterans with blast-mTBI versus control participants, p < 0.0001; q = 3.29 × 10-9 [Cohen's d, 1.38, 95% confidence interval (0.96, 1.79)]. The degree of left pallidum [18F]FDG-uptake correlated with the number of self-reported blast-mTBIs, r2 = 0.22; p < 0.0001. Greater [18F]FDG-uptake in the left pallidum provided excellent discrimination between Veterans with blast-mTBI and controls, with a receiver operator characteristic area under the curve of 0.859 (p < 0.0001) and likelihood ratio of 21.19 (threshold:SUVR ≥ 0.895). Deficits in executive function assessed using the Behavior Rating Inventory of Executive Function-Adult Global Executive Composite T-score were identified in Veterans with blast-mTBI compared with controls, p < 0.0001. Regression-based mediation analyses determined that in Veterans with blast-mTBI, increased [18F]FDG-uptake in the left pallidum-mediated executive function impairments, adjusted causal mediation estimate p = 0.021; total effect estimate, p = 0.039. Measures of working and prospective memory (Auditory Consonant Trigrams test and Memory for Intentions Test, respectively) were negatively correlated with left pallidum [18F]FDG-uptake, p < 0.0001, with mTBI as a covariate. Increased left pallidum [18F]FDG-uptake in Veterans with blast-mTBI compared with controls did not covary with dominant handedness or with motor activity assessed using the Unified Parkinson's Disease Rating Scale. Localized increased [18F]FDG-uptake in the left pallidum may reflect a compensatory response to functional deficits following blast-mTBI. Limited imaging resolution does not allow us to distinguish subregions of the pallidum; however, the significant correlation of our data with behavioral but not motor outcomes suggests involvement of the ventral pallidum, which is known to regulate motivation, behavior, and emotions through basal ganglia-thalamo-cortical circuits. Increased [18F]FDG-uptake in the left pallidum in blast-mTBI versus control participants was consistently identified using two different PET scanners, supporting the generalizability of this finding. Although confirmation of our results by single-subject-to-cohort analyses will be required before clinical deployment, this study provides proof of concept that [18F]FDG-PET bears promise as a readily available noninvasive biomarker for blast-mTBI. Further, our findings support a causative relationship between executive dysfunction and increased [18F]FDG-uptake in the left pallidum.

Cognitive dysfunction characteristics of multiple sclerosis with aging

BackgroundWe aimed to investigate the characteristics of cognitive impairment in older people with multiple sclerosis (MS). MethodsCross-sectional study that included participants that were examined with a common and comprehensive neuropsychological protocol. The subjects were matched by sociodemographic variables and the following groups were generated for comparisons: young MS versus healthy controls (HC) (n = 246), old MS versus HC (n = 198), young MS vs old MS (n = 226), MS vs Alzheimer's disease (AD)(n = 70), and MS vs Parkinson's disease (PD) (n = 62). The ICCoDiMS criteria were used to define cognitive impairment in MS. ResultsCognitive impairment was more frequent in young than old patients (70.8 % vs 52.2 %). Attention and speed processing is the most frequent cognitive domain impaired in MS (54.9 % of young MS vs 32.7 % of old MS). The frequency of impairment in attention/processing speed (54.9 % vs 32.7 %) and episodic memory (27.9 % vs 14.3) was higher in the young group than in the old group. There were no statistically significant differences in the distribution of impairment in executive function (46.0 % vs 35.3 %), visuospatial (17.9 % vs 9.5 %), and language (12.4 % vs 17.7 %). In those patients meeting the criteria for cognitive impairment, young MS patients showed lower performance in attention/processing speed tests. Conversely, old MS patients showed lower performance in episodic memory, verbal fluency, and planning. There were no differences in the correlations between SDMT and other neuropsychological tests in young and old patients, which suggests similar cognitive processes underlying SDMT performance in both groups. There were differences between old MS and prodromal AD, especially in episodic memory, while the cognitive profile of old MS was largely shared with PD. ConclusionsOur study found that the cognitive profile of MS is defined by a characteristic impairment in attention and processing speed, which is present during the lifespan. The impairment in processing speed is less prominent in old age, whereas the impairment of other cognitive functions becomes more relevant. These findings suggest potential differences in the pathophysiological processes associated with cognitive impairment between young and old ages that warrant further investigation.

The Role of Everyday Executive Function in Observed Social Symptoms of Autism Spectrum Disorder.

Recent research suggests there may be differences in the social presentations of autistic males and females. Camouflaging is believed to account for some of these differences and executive function (EF) may support compensatory social behaviors. As few studies have explored the role of sex and everyday EF when evaluating specific social difficulties among autistic youth, the present study seeks to address this. The Social Responsiveness Scale-2 (SRS-2) was used to measure types of social difficulties and the Behavioral Rating Inventory of Executive Function-2 (BRIEF-2) served as a measure of everyday EF. Four three-step hierarchical multiple regressions were conducted with SRS-2 social subscales as dependent variables. Autism symptom severity, BRIEF-2 EF Indices (i.e., behavioral, emotional, and cognitive regulation), and sex served as independent variables. Types of EF impairment significantly predicted social symptoms of autism. Behavioral dysregulation predicted all social symptoms assessed, cognitive dysregulation predicted social awareness and communication challenges, and emotion dysregulation predicted social motivation and communication difficulties. Sex significantly predicted social communication and cognition challenges, beyond the contributions of age, IQ, autism severity, and EF impairment. Findings from this study provide evidence for the contribution of EF to observed social symptoms of autism. Results suggest there may be sex-based differences in the relationship between EF and social problems for autistic youth. Implications and future directions are discussed.

The effect of financial stress on inhibitory control and economic decisions

Financial scarcity, both real and imagined, is associated with impaired executive functions and present-focused economic decisions. What is the mechanism that connects the lack of financial resources to these cognitive and behavioral effects? The present work will test the hypothesis that the experience of financial stress contributes to these deficits by reducing executive functions related to self-control and causing present-focused, real-world economic decisions. In a preliminary experiment (N = 215), we found support for the hypothesis that financial stress (as compared to social stress) causes a reduction in inhibitory control performance. In the registered study, we recruited participants (N = 1014) from diverse socioeconomic backgrounds and assessed inhibitory control before and after a financial stress manipulation, and economic preferences. The results did not support the hypothesis that momentary financial stress reduces inhibitory control or alters time preference. However, chronic financial stress was associated with reduced inhibitory control and VWM, and real-world economic decisions. Several interactions between SES and the effect of conditions highlight the relevance of a person's SES in the association between affective experiences and cognitive and behavioral responses. We discuss the implications of this work for future study of the association between SES, executive function, and economic decisions.

Biochemical, Biomarker, and Behavioral Characterization of the GrnR493X Mouse Model of Frontotemporal Dementia.

Heterozygous loss-of-function mutations in the progranulin gene (GRN) are a major cause of frontotemporal dementia due to progranulin haploinsufficiency; complete deficiency of progranulin causes neuronal ceroid lipofuscinosis. Several progranulin-deficient mouse models have been generated, including both knockout mice and knockin mice harboring a common patient mutation (R493X). However, the GrnR493X mouse model has not been characterized completely. Additionally, while homozygous GrnR493X and Grn knockout mice have been extensively studied, data from heterozygous mice is still limited. Here, we performed more in-depth characterization of heterozygous and homozygous GrnR493X knockin mice, which includes biochemical assessments, behavioral studies, and analysis of fluid biomarkers. In the brains of homozygous GrnR493X mice, we found increased phosphorylated TDP-43 along with increased expression of lysosomal genes, markers of microgliosis and astrogliosis, pro-inflammatory cytokines, and complement factors. Heterozygous GrnR493X mice did not have increased TDP-43 phosphorylation but did exhibit limited increases in lysosomal and inflammatory gene expression. Behavioral studies found social and emotional deficits in GrnR493X mice that mirror those observed in Grn knockout mouse models, as well as impairment in memory and executive function. Overall, the GrnR493X knockin mouse model closely phenocopies Grn knockout models. Lastly, in contrast to homozygous knockin mice, heterozygous GrnR493X mice do not have elevated levels of fluid biomarkers previously identified in humans, including neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in both plasma and CSF. These results may help to inform pre-clinical studies that use this Grn knockin mouse model and other Grn knockout models.