Alterations In Executive Functions Research Articles

Executive Functions in a Patient with Low-Grade Glioma of the Central Nervous System: A Case Report.

Central nervous system tumors produce adverse outcomes in daily life, although low-grade gliomas are rare in adults. In neurological clinics, the state of impairment of executive functions goes unnoticed in the examinations and interviews carried out. For this reason, the objective of this study was to describe the executive function of a 59-year-old adult neurocancer patient. This study is novel in integrating and demonstrating biological effects and outcomes in performance evaluated by a neuropsychological instrument and psychological interviews. For this purpose, pre- and post-evaluations were carried out of neurological and neuropsychological functioning through neuroimaging techniques (iRM, spectroscopy, electroencephalography), hospital medical history, psychological interviews, and the Wisconsin Card Classification Test (WCST). There was evidence of deterioration in executive performance, as evidenced by the increase in perseverative scores, failure to maintain one's attitude, and an inability to learn in relation to clinical samples. This information coincides with the evolution of neuroimaging over time. Our case shows that the presence of the tumor is associated with alterations in executive functions that are not very evident in clinical interviews or are explicit in neuropsychological evaluations. In this study, we quantified the degree of impairment of executive functions in a patient with low-grade glioma in a middle-income country where research is scarce.

Emotional and behavioral alterations and their relationship with executive functioning in the pediatric population with autism spectrum disorder and epilepsy: a comparative study.

The pediatric population with Autism Spectrum Disorder (ASD) and epilepsy presents behavioral and emotional alterations that hinder their correct developmental maturation as well as their integration in different contexts such as school, family or social. This population shows atypical behavioral and emotional patterns, with difficulties in emotional regulation, understanding of emotions, aggressiveness, or low frustration tolerance. They also present alterations in executive functions, which significantly influence the emotional and behavioral characteristics of this population. Research suggests that epilepsy worsens the emotional, behavioral, and executive functioning status. To explore differences in behavioral, emotional, and executive functioning profile in individuals with a diagnosis of ASD, epilepsy, and ASD with epilepsy. In this quasi-experimental and cross-sectional study, a total of 170 participants were selected and distributed into three groups: a group of participants with ASD, a group with epilepsy, and a group of participants with ASD and epilepsy. The SENA, BASC-3, and ENFEN tests were administered to verify the behavioral, emotional, and executive functioning profile in the three groups. The results indicate that individuals diagnosed with ASD and epilepsy present greater emotional, behavioral, and executive functioning alterations compared to those who only present ASD or epilepsy. Individuals with ASD and epilepsy present significant alterations in emotional, behavioral, and executive functioning processes, which hinder their adaptation to different contexts, as well as decreasing their quality of life and that of their family.

Neurocognitive Analysis of Low-level Arsenic Exposure and Executive Function Mediated by Brain Anomalies Among Children, Adolescents, and Young Adults in India

Arsenic, a contaminant of groundwater and irrigated crops, is a global public health hazard. Exposure to low levels of arsenic through food extends well beyond the areas with high arsenic content in water. To identify cognitive impairments following commonly prevalent low-level arsenic exposure and characterize their underlying brain mechanisms. This multicenter population-based cohort study analyzed cross-sectional data of the Indian Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA) cohort, recruited between November 4, 2016, and May 4, 2019. Participants aged 6 to 23 years were characterized using deep phenotyping measures of behavior, neuropsychology, psychopathology, brain neuroimaging, and exposure to developmental adversities and environmental neurotoxins. All analyses were performed between June 1, 2020, and December 31, 2021. Arsenic levels were measured in urine as an index of exposure. Executive function measured using the cVEDA neuropsychological battery, gray matter volume (GMV) from T1-weighted magnetic resonance imaging, and functional network connectivity measures from resting state functional magnetic resonance imaging. A total of 1014 participants aged 6 to 23 years (589 male [58.1%]; mean [SD] age, 14.86 [4.79] years) were included from 5 geographic locations. Sparse-partial least squares analysis was used to describe a negative association of arsenic exposure with executive function (r = -0.12 [P = 5.4 × 10-4]), brain structure (r = -0.20 [P = 1.8 × 10-8]), and functional connectivity (within network, r = -0.12 [P = 7.5 × 10-4]; between network, r = -0.23 [P = 1.8 × 10-10]). Alterations in executive function were partially mediated by GMV (b = -0.004 [95% CI, -0.007 to -0.002]) and within-network functional connectivity (b = -0.004 [95% CI, -0.008 to -0.002]). Socioeconomic status and body mass index moderated the association between arsenic and GMV, such that the association was strongest in participants with lower socioeconomic status and body mass index. The findings of this cross-sectional study suggest that low-level arsenic exposure was associated with alterations in executive functioning and underlying brain correlates. These results indicate potential detrimental consequences of arsenic exposure that are below the currently recommended guidelines and may extend beyond endemic risk areas. Precision medicine approaches to study global mental health vulnerabilities highlight widespread but potentially modifiable risk factors and a mechanistic understanding of the impact of low-level arsenic exposure on brain development.

Reinforcer value moderates the effects of prenatal alcohol exposure on learning and reversal.

Fetal Alcohol Spectrum Disorders (FASD) are the leading cause of preventable developmental disability and are commonly characterized by alterations in executive function. Reversal learning tasks are reliable, cross-species methods for testing a frequently impaired aspect of executive control, behavioral flexibility. Pre-clinical studies commonly require the use of reinforcers to motivate animals to learn and perform the task. While there are several reinforcers available, the most commonly employed are solid (food pellets) and liquid (sweetened milk) rewards. Previous studies have examined the effects of different solid rewards or liquid dietary content on learning in instrumental responding and found that rodents on liquid reward with higher caloric content performed better with increased response and task acquisition rate. The influence of reinforcer type on reversal learning and how this interacts with developmental insults such as prenatal alcohol exposure (PAE) has not been explored. We tested whether reinforcer type during learning or reversal would impact an established deficit in PAE mice. We found that all male and female mice on liquid reward, regardless of prenatal exposure were better motivated to learn task behaviors during pre-training. Consistent with previous findings, both male and female PAE mice and Saccharine control mice were able to learn the initial stimulus reward associations irrespective of the reinforcer type. During the initial reversal phase, male PAE mice that received pellet rewards exhibited maladaptive perseverative responding whereas male mice that received liquid rewards performed comparable to their control counterparts. Female PAE mice that received either reinforcer types did not exhibit any deficits on behavioral flexibility. Female saccharine control mice that received liquid, but not pellet, rewards showed increased perseverative responding during the early reversal phase. These data suggest that reinforcer type can have a major impact on motivation, and therefore performance, during reversal learning. Highly motivating rewards may mask behavioral deficits seen with more moderately sought rewards and gestational exposure to the non-caloric sweetener, saccharine, can impact behavior motivated by those reinforcers in a sex-dependent manner.

Executive functioning in children with posterior cortex epilepsy compared to temporal and frontal lobe epilepsies

ObjectivePeople with epilepsy are at an increased risk of experiencing executive dysfunction, particularly those with frontal lobe epilepsy (FLE). The literature has also demonstrated alterations in executive functioning (EF) in patients with temporal lobe epilepsy (TLE). However, few studies have examined the neuropsychological profile of posterior cortex epilepsy (PCE), and little attention has been given to cognitive impairments in the pediatric population with PCE. This study aims to investigate EF performance in children with drug-resistant PCE compared to patients with FLE and TLE. MethodsWe analyzed neuropsychological data from 217 patients aged 6–18 years who underwent preoperative evaluation for epilepsy surgery. The EF of patients with PCE was compared to patients with FLE and TLE. ResultsThere was no significant difference in Full-Scale Intelligence Quotient (FSIQ) means between groups. However, we found a significant effect of brain region on the Coding task, in which patients with PCE and FLE performed worse than those with TLE (p = 0.034). We also observed performance differences between groups on the Stroop test (p = 0.005), with patients with PCE and FLE performing worse than the TLE group. SignificanceThese findings suggest that children with PCE have alterations in their EF that are similar to the deficits found in FLE compared to patients with TLE. This emphasizes the importance of understanding the neuroanatomy of executive functions and the model of neural networks extending beyond the prefrontal cortex.

Neurological Manifestations of Long COVID: A Single-Center One-Year Experience.

We report our single-center experience on the neurological manifestations of long COVID. This is a retrospective observational study. All consecutive patients referred to the neurological long COVID outpatient clinic of our institute from January 21 2021 to December 9 2021 underwent a general neurological objective examination. Treatments and investigations (brain MRI, neuropsychological evaluation, or others) were prescribed on an individual basis as per standard clinical practice. A follow-up visit was performed when appropriate. Descriptive statistics were presented as absolute and relative frequencies for categorical variables and as means, median, and ranges for continuous variables. One hundred and three patients were visited (mean age 50.5 ±36 years, 62 females). The average time from acute COVID-19 infection to the first visit to our outpatient clinic was 243 days. Most patients presented with a mild form of acute COVID-19, with only 24 cases requiring hospitalization. The neurological symptoms mostly (n=70/103, 68%) started during the acute phase (before a negative swab for SARS-CoV-2). The most frequent acute manifestations reported, which lately became persistent, were fatigue (n=58/103, 56%), olfactory/taste dysfunction (n=58/103, 56%), headache (n=47/103, 46%), cognitive disorders (n=46/103, 45%), sleep disorders (n=30/103, 29%), sensitivity alterations (n=29/103, 28%), and dizziness (n=7/103, 7%). Tremor was also reported (n=8/103, 7%). Neuropsychological evaluation was performed in 30 patients and revealed alterations in executive functions (n=6/30, 20%), memory (n=11/30, 37%), with pathological depressive (n=9/30, 30%) and anxiety (n=8/30, 27%) scores. Brain MRIs have been performed in 41 cases, revealing nonspecific abnormal findings only in 4 cases. Thirty-six patients underwent a follow-up, where a general improvement was observed but rarely (n=2/36) a complete recovery. The majority of patients presenting persistent neurological symptoms (most frequently fatigue, cognitive disorders, and olfactory dysfunctions) developed a previous mild form of COVID-19. Further studies are required to develop therapeutic strategies.

Comparison of Cognitive and Behavioral Profiles of Individuals with Attention Deficit Hyperactivity Disorder and Dyslexia

Attention Deficit Hyperactivity Disorder and Developmental Dyslexia are disorders usually diagnosed in childhood and adolescence and affect different cognitive functions, however, with differences in central deficits. There is a consensus that children with Attention Deficit Hyperactivity Disorder manifest alterations in attention and executive functioning. Meanwhile, a growing number of researchers that investigated and described attentional and other executive function alterations in affected Dyslexia individuals. Therefore, our study aimed to compare the cognitive and behavioral profiles of 21 children with Attention Deficit Hyperactivity Disorder (n=7), Dyslexia (n=6), and a control group (n=8), ages 6 to 14 years old, evaluated from January 2022 to July 2023. We excluded children with other neurodevelopmental disorders or neurologic diseases. The results showed that in tasks of working memory and cognitive flexibility, the group with Attention Deficit Hyperactivity Disorder presented higher averages than the children with Dyslexia. Furthermore, participants with Attention Deficit Hyperactivity Disorder committed more mistakes in attentional tests, mainly in alternating attention, than the Dyslexia group (z = -8.548; p=0.029). Furthermore, participants with Attention Deficit Hyperactivity Disorder had higher means for externalizing problems (Average: 62.43; Standard Deviation: 8.36) when compared to the group with Dyslexia (Average: 57.50; Standard Deviation: 5.09), as well as dyslexics had higher means for behavior problems internalizing (Average: 66.00; Standard Deviation: 11.63) than the Attention Deficit Hyperactivity Disorder group (Average: 58.00; Standard Deviation: 8.16). The results found in this study showed that children with Attention Deficit Hyperactivity Disorder had higher averages than the group with Dyslexia in attention and executive functions and indicated the presence of a heterogeneous cognitive and behavioral profile among the participants, however, the clinical groups showed significant impairments in attention, executive functions and behavior, which can have an impact on the functionality and quality of life of these children.

Amyloid Beta Alters Prefrontal-dependent Functions Along with its Excitability and Synaptic Plasticity in Male Rats

Prefrontal cortex (PFC)-related functions, such as working memory (WM) and cognitive flexibility (CF), are among the first to be altered at early stages of Alzheimer’s disease (AD). Likewise, transgenic AD models carrying different AD-related mutations, mostly linked to the overproduction of amyloid beta (Aβ) and other peptides, show premature behavioral and functional symptoms associated with PFC alterations. However, little is known about the effects of intracerebral or intra-PFC Aβ infusion on WM and CF, as well as on pyramidal cell excitability and plasticity. Thus, here we evaluated the effects of a single Aβ injection, directly into the PFC, or its intracerebroventricular (icv) application, on PFC-dependent behaviors and on the intrinsic and synaptic properties of layer V pyramidal neurons in PFC slices. We found that a single icv Aβ infusion reduced learning and performance of a delayed non-matching-to-sample WM task and prevented reversal learning in a matching-to-sample version of the task, several weeks after its infusion. The inhibition of WM performance was reproduced more potently by a single PFC Aβ infusion and was associated with Aβ accumulation. This behavioral disruption was related to increased layer V pyramidal cell firing, larger sag membrane potential, increased fast after-hyperpolarization and a failure to sustain synaptic long-term potentiation, even leading to long-term depression, at both the hippocampal-PFC pathway and intracortical synapses. These findings show that Aβ can affect PFC excitability and synaptic plasticity balance, damaging PFC-dependent functions, which could constitute the foundations of the early alterations in executive functions in AD patients.

Coupling cognitive and brainstem dysfunction in multiple sclerosis-related chronic neuropathic limb pain.

Chronic pain in multiple sclerosis is common and difficult to treat. Its mechanisms remain incompletely understood. Dysfunction of the descending pain modulatory system is known to contribute to human chronic pain conditions. However, it is not clear how alterations in executive function influence this network, despite healthy volunteer studies linking function of the descending pain modulatory system, to cognition. In adults with multiple sclerosis-associated chronic neuropathic limb pain, compared to those without pain, we hypothesized altered functional connectivity of the descending pain modulatory system, coupled to executive dysfunction. Specifically we hypothesized reduced mental flexibility, because of potential importance in stimulus reappraisal. To investigate these hypotheses, we conducted a case-control cross-sectional study of 47 adults with relapsing remitting multiple sclerosis (31 with chronic neuropathic limb pain, 16 without pain), employing clinical, neuropsychological, structural, and functional MRI measures. We measured brain lesions and atrophy affecting descending pain modulatory system structures. Both cognitive and affective dysfunctions were confirmed in the chronic neuropathic limb pain group, including reduced mental flexibility (Delis Kaplan Executive Function System card sorting tests P < 0.001). Functional connectivity of rostral anterior cingulate and ventrolateral periaqueductal gray, key structures of the descending pain modulatory system, was significantly lower in the group experiencing chronic neuropathic pain. There was no significant between-group difference in whole-brain grey matter or lesion volumes, nor lesion volume affecting white matter tracts between rostral anterior cingulate and periaqueductal gray. Brainstem-specific lesion volume was higher in the chronic neuropathic limb pain group (P = 0.0017). Differential functional connectivity remained after correction for brainstem-specific lesion volume. Gabapentinoid medications were more frequently used in the chronic pain group. We describe executive dysfunction in people with multiple sclerosis affected by chronic neuropathic pain, along with functional and structural MRI evidence compatible with dysfunction of the descending pain modulatory system. These findings extend understanding of close inter-relationships between cognition, function of the descending pain modulatory system, and chronic pain, both in multiple sclerosis and more generally in human chronic pain conditions. These findings could support application of pharmacological and cognitive interventions in chronic neuropathic pain associated with multiple sclerosis.

Neuropsychological changes in FMR1 premutation carriers and onset of fragile X-associated tremor/ataxia syndrome

BackgroundCarriers of the FMR1 premutation are at increased risk of developing a late-onset progressive neurodegenerative disease, fragile X-associated tremor/ataxia syndrome (FXTAS), characterized by intention tremor, gait ataxia, and cognitive decline. Cross-sectional studies to date have provided evidence that neuropsychological changes, such as executive function alterations, or subtle motor changes, may precede the onset of formal FXTAS, perhaps characterizing a prodromal state. However, the lack of longitudinal data has prevented the field from forming a clear picture of progression over time within individuals, and we lack consensus regarding early markers of risk and measures that may be used to track response to intervention.MethodsThis was a longitudinal study of 64 male FMR1 premutation carriers (Pm) without FXTAS at study entry and 30 normal controls (Nc), aged 40 to 80 years (Pm M = 60.0 years; Nc M = 57.4 years). Fifty of the Pm and 22 of the Nc were re-assessed after an average of 2.33 years, and 37 Pm and 20 Nc were re-assessed a third time after an average of another 2.15 years. Eighteen of 64 carriers (28%) converted to FXTAS during the study to date. Neuropsychological assessments at each time point, including components of the Cambridge Neuropsychological Test Automated Battery (CANTAB), tapped domains of episodic and working memory, inhibitory control, visual attention, planning, executive control of movement, and manual speed and dexterity. Age-based mixed models were used to examine group differences in change over time on the outcomes in the full sample, and differences were further evaluated in 15 trios (n = 45; 15 Pm “converters,” 15 Pm “nonconverters,” 15 Nc) that were one-one matched on age, education, and socioeconomic status.ResultsCompared to Nc, Pm showed significantly greater rates of change over time in visual working memory, motor dexterity, inhibitory control, and manual movement speed. After multiple comparison correction, significant effects remained for motor dexterity. Worsening inhibitory control and slower manual movements were related to progression in FXTAS stage, but these effects became statistically non-significant after correcting for multiple comparisons. Higher FMR1 mRNA correlated with worsening manual reaction time but did not survive multiple comparisons and no other molecular measures correlated with neuropsychological changes. Finally, trio comparisons revealed greater rate of decline in planning and manual movement speed in Pm converters compared to Pm nonconverters.ConclusionsAccelerated decline in executive function and subtle motor changes, likely mediated by frontocerebellar circuits, may precede, and then track with the emergence of formal FXTAS symptoms. Further research to develop and harmonize clinical assessment of FMR1 carriers across centers is needed to prepare for future prophylactic and treatment trials for this disorder.

Executive functions and eating behavior: Commentary on Steegers et al. (2021).

Alterations in executive functions have repeatedly been found in individuals suffering from eating and weight disorders. However, less is known about how these cognitive processes might contribute to the etiology of the disorders, as large prospective population-based studies have been missing. Here, we comment on the results of Steegers et al. (2021), a study that helped to fill this gap with a focus on set-shifting abilities predicting symptoms of anorexia nervosa (AN) in children. The main goal of this commentary is to encourage further interpretation of the population-based data beyond its relevance to AN. More specifically, we discuss the role of impaired inhibition as a risk factor for weight gain and obesity.

Functional brain rewiring and altered cortical stability in ulcerative colitis

Despite recent advances, there is still a major need to better understand the interactions between brain function and chronic gut inflammation and its clinical implications. Alterations in executive function have previously been identified in several chronic inflammatory conditions, including inflammatory bowel diseases. Inflammation-associated brain alterations can be captured by connectome analysis. Here, we used the resting-state fMRI data from 222 participants comprising three groups (ulcerative colitis (UC), irritable bowel syndrome (IBS), and healthy controls (HC), N = 74 each) to investigate the alterations in functional brain wiring and cortical stability in UC compared to the two control groups and identify possible correlations of these alterations with clinical parameters. Globally, UC participants showed increased functional connectivity and decreased modularity compared to IBS and HC groups. Regionally, UC showed decreased eigenvector centrality in the executive control network (UC < IBS < HC) and increased eigenvector centrality in the visual network (UC > IBS > HC). UC also showed increased connectivity in dorsal attention, somatomotor network, and visual networks, and these enhanced subnetwork connectivities were able to distinguish UC participants from HCs and IBS with high accuracy. Dynamic functional connectome analysis revealed that UC showed enhanced cortical stability in the medial prefrontal cortex (mPFC), which correlated with severe depression and anxiety-related measures. None of the observed brain changes were correlated with disease duration. Together, these findings are consistent with compromised functioning of networks involved in executive function and sensory integration in UC.

Cognition in prodromal Parkinson's disease.

One characteristic of Parkinson's disease (PD) is a prodromal phase, lasting many years during which both pre-clinical motor and non-motor symptoms occur. Around one-fifth of patients with PD manifest mild cognitive impairment at time of clinical diagnosis. Thus, important challenges are to define the time of onset of cognitive dysfunction in the prodromal phase of PD, and to define its co-occurrence with other specific characteristics. Evidence for cognitive change in prodromal PD comes from various study designs, including both longitudinal and cross-sectional approaches with different target groups. These studies support the concept that changes in global cognitive function and alterations in executive functions occur, and that these changes may be present up to 6 years before clinical PD diagnosis. Notably, this evidence led to including global cognitive impairment as an independent prodromal marker in the recently updated research criteria of the Movement Disorder Society for prodromal PD. Knowledge in this field, however, is still at its beginning, and evidence is sparse about many aspects of this topic. Further longitudinal studies including standardized assessments of global and domain-specific cognitive functions are needed to gain further knowledge about the first appearance, the course, and the interaction of cognitive deficits with other non-motor symptoms in prodromal stage PD. Treatment approaches, including non-pharmacological interventions, in individuals with prodromal PD might help to prevent or delay cognitive dysfunction in early PD.

Executive Dysfunction in Adolescent with Obesity: A Systematic Review

Obesity has been linked to low cognitive performance throughout the human life span. Alterations relate to attention, memory, language, and executive function. However, the obesity-executive function association remains unclear in adolescents. This study presents a systematic review of executive function alterations in adolescents with obesity. A search equation was proposed (Executive dysfunction AND Obesity AND Adolescents), with sixty studies meeting the inclusion criteria in the Clarivate Analytics Web of Science Core Collection database. A bibliometric analysis was conducted to identify the importance of the research topic and a citation network was built to establish the lines of research. Finally, the citation network was exported to Gephi to visualize the research groups studying the topic. Findings suggest 4 lines of research: (a) structural and functional brain abnormalities in adolescents with obesity, (b) inhibitory control alterations in adolescents with obesity, (c) effects of physical and cognitive activity on the executive function of adolescents with obesity, and (d) working memory alterations in adolescents with obesity. Obese adolescents were found to prefer immediate rewards to long-term ones. Nevertheless, effective interventions increase the intake of fruit and vegetables and reduce that of calorie-dense food. The authors recommend additional longitudinal studies to assess whether executive function alterations are either a cause or a consequence of adolescent obesity.

The Cognitive Consequences of the COVID-19 Pandemic on Members of the General Population in Italy: A Preliminary Study on Executive Inhibition.

The pandemic period which has characterized the last two years has been associated with increasingly worsening psychological conditions, and previous studies have reported severe levels of anxiety, mood disorder, and psychopathological alteration in the general population. In particular, worldwide populations have appeared to present post-traumatic stress symptoms (PTSS). Surprisingly, no studies have evaluated the effect of COVID-related PTSS on cognitive functioning. This study focused on the association between high levels of PTSS related to COVID-19 and alterations in executive functioning by considering executive inhibitions in populations not infected by the virus. Ninety respondents from the Italian population participated in the study. A higher percentage of PTSS was reported. Moreover, respondents with high post-traumatic symptomatology presented deficits in the inhibition of preponderant responses, demonstrating an executive deficit which could be expressed by a difficulty in controlling goal-directed actions. This was underlined by worse performances in elaborating incongruent stimuli in the Stroop task and no-go stimuli in the Go/No-Go task. This report presents preliminary findings underlining the effect of the COVID-19 pandemic on cognitive functions. The results confirmed a persistently higher post-traumatic symptomatology related to the COVID-19 pandemic in the Italian population and highlighted an association with cognitive inhibition impairment.

High cognitive demand tasks may detect mild alterations in executive functions in American football players: A pilot study

High cognitive demand tasks may detect mild alterations in executive functions in American football players: A pilot study

Volume of hippocampal subfields and cognitive deficits in neuromyelitis optica spectrum disorders.

Aquaporin-4 (AQP4) water channel is involved in hippocampal plasticity and is the target of neuromyelitis optica spectrum disorders (NMOSD) autoimmunity. We measured volumes of hippocampal subfields and their association with cognitive performance in AQP4-seropositive NMOSD patients. Global and regional hippocampal volumes were derived from 28 AQP4-seropositive NMOSD patients and 101 healthy controls (HC) from 3D-T1-weighted images. Normalized brain volumes were also calculated. A neuropsychological evaluation, including the Brief Repeatable Battery of Neuropsychological Tests, was performed in patients. Based on HC data, we estimated mean z-scores of volumes in the whole NMOSD group and compared them according to the status of global and domain-selective cognitive impairment. Global cognitive impairment was detected in 46.4% of NMOSD patients, with attentive (60.7%) and executive (21.4%) domains being the most affected. NMOSD patients had left hippocampal atrophy at global (p=0.012) and regional level (fimbria, Cornu Ammonis [CA] 3, molecular layer, dentate gyrus [DG], and subicular complex, p values ranging between 0.033 and <0.001). On the right side the fimbria and hippocampal tail were atrophic (p=0.024 for both). Cognitively impaired patients showed atrophy in the left CA3 and CA4 (p=0.025-0.028), while patients presenting verbal and visual memory impairment had significant CA3 and DG atrophy. Those patients with attentive or executive impairment had preserved brain and hippocampal volumes. NMOSD patients showed hippocampal atrophy associated with verbal and visual memory impairment. Such damage did not explain attention and executive function alterations, which were the most common cognitive deficits in this population.

Amyloid and anatomical correlates of executive functioning in middle-aged offspring of patients with late-onset Alzheimer's disease.

A traditional hallmark of cognitive impairment associated with late-onset Alzheimer´s disease (LOAD) is episodic memory impairment. However, early alterations have been identified in brain regions associated with executive function in asymptomatic, middle-age offspring of patients with LOAD (O-LOAD) compared to those with no family history. We hypothesized that executive function among O-LOAD would correlate with structural and amyloid brain imaging differently from those without a family history of LOAD (control subjects, CS). Executive function, cortical thickness, and in-vivo Aβ deposits were quantified in 30 O-LOAD and 25 CS. Associations were observed among O-LOAD only. Cortical thickness in the left lateral orbitofrontal cortex was positively associated with Design Fluency. The Stroop Color and Word Test, correlated positively with right rostral mid-frontal cortex thickness. Trails Making Test-B was inversely related to left medial orbitofrontal thickness. Tower of London total time was positively associated with β-amyloid deposition in the right precuneus. These results support previous evidence that early executive dysfunction might reflect subtle, early changes in persons at risk of LOAD and suggests that executive function alterations deserve further exploration in the LOAD literature.

Selective dopaminergic effects on attention and memory in male mice exposed to Methylmercury during adolescence

Gestational exposure to methylmercury disrupts dopamine-mediated behavior and produces heightened sensitivity to monoamine agonists later in life. This has been reported and replicated following both pre- and post-natal exposure. Impacts of methylmercury when exposure occurs during the sensitive period of adolescence, a key period of dopaminergic development, remain underexplored. There have been variable results thus far in studies investigating links between adolescent exposure to methylmercury and alterations in executive function and altered sensitivity to monoamine agonists. The current study was designed to investigate adolescent exposure by exposing male mice to 0, 0.3, or 3 ppm methylmercury during adolescence and training them in a hybrid task to assess two executive functions, attention and memory, in adulthood. Behavior in these animals was probed with a range of doses of the dopamine agonist, d-amphetamine, and the norepinephrine agonist, desipramine. Attention and memory in these mice were sensitive to disruption by d-amphetamine and interacted with methylmercury exposure. Choice latencies were also longer in the MeHg-exposed mice. Desipramine did not affect behavior in these animals nor did it interact with methylmercury. It is concluded that methylmercury-related inhibition of behavior observed in this study were differentially sensitive to acute disruption in dopamine, but not norepinephrine, neurotransmission.

Threat-Modulation of Executive Functions—A Novel Biomarker of Depression?

Background: Alterations in executive functions, emotion regulation, and their interaction are common concomitants of depression. Executive dysfunction frequently lingers after treatment, has adverse effects on daily life, and predisposes to recurrence of depression. Yet, sensitive measures of executive function for reliable assessment of cognitive outcomes are still lacking in clinical practice. To better understand the impact of depression and its most effective treatment, electroconvulsive therapy (ECT), on cognition, we assessed executive functions pre- and post-ECT and whether objective measures reflecting alterations in emotion–executive function interaction correlate with depression severity or with cognitive outcome.Methods: Executive functions were assessed in 21 patients with major depressive disorder (MDD) before and after ECT using subjective measures from the Behavior Rating Inventory of Executive Function—Adult version (BRIEF-A) and objective cognitive performance measures derived from computer-based test of executive function, Executive Reaction Time (RT) Test. In addition, we created novel indices reflecting emotional modulation of cognitive performance by subtracting different performance measures in the context of neutral distractors from those in the context of threat-related distractors. We correlated these indices with Beck Depression Inventory (BDI) and BRIEF-A scores.Results: Depression was significantly alleviated, and executive functions improved post-ECT, as seen in reduced BDI scores, BRIEF-A scores, and number of errors in Executive RT Test. Pre-ECT BDI scores correlated with threat modulation of RT (tmRT) and threat modulation of working memory (tmWM). Post-ECT tmRT correlated with several Behavioral Regulation scales and tmWM with several Metacognition scales of BRIEF-A.Conclusion: While caution is warranted, results from both subjective and objective measures suggest that ECT significantly improves executive functions and emotion regulation along with alleviation of depression. Novel indices derived from threat modulation of executive function and working memory show promise as objective biomarkers of depression severity pre-ECT and cognitive outcome post-ECT with potential for guiding depression treatments.