Impaired Executive Function Research Articles

Cognitive deficits with chemotherapy in women with breast cancer: a bibliographic revisión

Patients with breast cancer may experience cognitive difficulties from chemotherapy. This alteration is called Chemoinduced Cognitive Impairment, also known as Chemobrain or Chemofog. To identify the cognitive profile and the characteristics of the neuropsychological assessment in this population. Method: PubMed, SpringerLink and SciELO databases were revised. Articles from 1994 to September 2021 were selected. Keywords related to the study topic were used. Chemotherapy can cause cognitive impairment between 15 and 50% of women. This disturbance may be from multiple aetiologies and can be associated with biological factors and functional and/or structural changes of the CNS. Sociodemographic, clinical and psychological factors should be considered as modulating variables. It manifests mainly with memory problems, executive function, attention and processing speed impairment. It can be measured through neuropsychological evaluation instruments. We suggest that chemo-induced cognitive impairment should be included to the informed consent. Further development of longitudinal studies complemented with neuroimages that allow us to advance in the knowledge of this problem is recommended. A neuropsychological protocol is proposed, which includes screening tests, clinical scales, specific cognitive tests and quality of life questionnaires, within the recommendations of the International Cognition and Cancer Task Force.

Evaluation of the Relationships between Irisin Levels and Cognitive Functions in Individuals with Schizophrenia.

: Irisin is a myokine that is involved in neurogenesis, neuronal proliferation, and neuronal differentiation. Many research examine the relationship between irisin and schizophrenia. In this study, we aimed to evaluate the relationship between irisin levels and cognitive functions in individuals with schizophrenia. : Ninety-six individuals who were diagnosed with schizophrenia were included. The Brief Psychiatric Rating Scale (BPRS) was used to assess disease severity. To evaluate the cognitive functions of the patients, the trail-making test was evaluated with the A and B forms and the verbal memory processes scale. After a 12-hour night fast, samples of fasting blood were obtained from the participants. : There was no significant correlation between irisin, duration of disease, and BPRS total score. In the analysis performed, a positive correlation was found between the plasma irisin level and the error score of the trail-making test form B. Other than that, no correlation was found between irisin level and cognitive performance in schizophrenia patients. In addition, in subgroup analysis between genders, it was determined that the duration of the trail-making test B was longer in female schizophrenia patients. : In this study, there was a positive correlation between the trail-making test B-form error scores and the irisin levels. This relationship between impaired executive functions and irisin levels may suggest that the irisin level is increased as compensation for the impairment in executive functions. More research is needed to understand the role of irisin in cognitive impairment and schizophrenia.

Identifying subgroups of attention-deficit/hyperactivity disorder from the psychopathological and neuropsychological profiles.

The Research Domain Criteria (RDoC) advocates the dimensional approach in characterizing mental disorders. We followed RDoC to characterize children with ADHD using profiling based on the cognitive and psychopathological domains. We aimed to identify and validate ADHD subtypes with different clinical characteristics and functional impairments. We recruited 362 drug-naïve children with ADHD and 103 typically developing controls. The cluster analysis was used to identify subgroups based on the Child Behaviour Checklist (CBCL) and the Behaviour Rating Inventory of Executive Function (BRIEF). The subgroups' clinical characteristics and functional impairments were assessed using the WEISS Functional Impairment Rating Scale-Parent Report (WFIRS-P) and the Conners Parent Symptom Questionnaire (PSQ). The cluster analysis yielded four subgroups: (1) ADHD with severe impairment in psychopathology and executive functions (EF), (2) ADHD with mild executive dysfunctions and normal-level psychopathology, (3) ADHD with severe externalizing problems and (4) ADHD with severe executive dysfunctions. These subgroups showed different clinical characteristics and degrees of functional impairment. The EF impairment group displayed more serious learning problems and worse life skills than the externalizing group. The two groups with externalizing problems (i.e. the severe impairment group and the externalizing group) both exhibited higher rates of the combined subtype of ADHD and higher rates of comorbid ODD. Different subtypes of ADHD displayed different profiles of internalizing and externalizing problems and levels of executive dysfunctions. In particular, the subtype with severe impairment in EF exhibited more learning problems and worse life skills, suggesting EF is a critical target for intervention in children with ADHD.

Reported neurological symptoms after severe acute respiratory syndrome coronavirus type 2 (SARS CoV-2) infection: a systematic diagnostic approach.

Following increasing demands of patients with suspected neurological symptoms after infection with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the Department of Neurology at the Medical University of Vienna established a new outpatient clinic to systematically assess, diagnose and document neurological complaints potentially associated with a prior SARS-CoV-2 infection. The data presented here include prospectively collected 156 outpatients from May 2021 to April 2022. Patients underwent semi-standardized interviewing about symptoms with reported onset after SARS CoV-2 infection, neurological examination, and comprehensive diagnostic workup. Reported new-onset symptoms after infection included fatigue (77.6%), subjective cognitive impairment (72.4%), headache (47.7%), loss of smell and/or taste (43.2%), and sleep disturbances (42.2%). Most patients had a mild coronavirus disease (COVID-19) disease course (84%) and reported comorbidities (71%), thereof the most frequent were psychiatric disorders (34%). Frequency of symptoms was not associated with age, sex, or severity of COVID-19 course. A comprehensive diagnostic workup revealed no neurological abnormalities in the clinical examination, electrophysiological, or imaging assessments in the majority of patients (n=143, 91.7%). Neuropsychological assessment of a subgroup of patients (n = 28, 17.9%) showed that cognitive impairments in executive functions and attention, anxiety, depression, and somatization symptoms were highly common. In this systematic registry we identified fatigue, cognitive impairment, and headache as the most frequently reported persisting complaints after SARS-CoV-2 infection. Structural neurological findings were rare. We suspect a link between the growing burden of the COVID pandemic on personal lives and the increase in reported neurological and psychiatric complaints.

Cross-Validating the Executive Errors Scale of the Repeatable Battery for the Assessment of Neuropsychological Status.

The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was developed to briefly measure a broad range of cognitive abilities, but it initially lacked a scale to evaluate executive functioning. Robert Spencer and colleagues recently created an Executive Errors scale (RBANS-EE) that quantified executive functioning (EF) errors committed during four RBANS subtests: List Learning, Semantic Fluency, Coding, and List Recall. In the present paper we cross-validated the RBANS-EE with a sample of 234 U.S. military veterans (M AGE = 67.2, SD = 11.5years; M EDUCATION = 13.3, SD = 2.4years) who completed the RBANS and various EF criterion measures as part of neuropsychological assessments they underwent during their clinical care. We found the RBANS-EE to be significantly correlated with most of the criterion EF measures. The RBANS-EE scale demonstrated modest ability to classify EF impairment at mild and severe levels; and, similarly, the RBANS-EE was modestly capable of accurately classifying those veteran respondents who were determined to have or to not have a neurocognitive disorder. Overall, the RBANS-EE can be quickly calculated, adds no administration time to an RBANS assessment, and yields useful scores to screen for EF dysfunction without replacing standalone EF tests.

Resolution of elevated interleukin-6 after surgery is associated with return of normal cognitive function

BackgroundUnresolved surgical inflammation might induce chronic cognitive decline in older adults. Although inflammatory biomarkers have been correlated with perioperative cognitive impairment and delirium, the effects of prolonged inflammation on cognition are not well studied. This prospective cohort study investigated 1-yr dynamics in plasma interleukin-6 levels and executive function. MethodsPatients undergoing major surgery (n=170) aged ≥65 yr completed Trail Making Test B and other neuropsychological assessments with plasma interleukin-6 levels collected on postoperative days 1–9 and 90, and at 1-yr. Mixed-effects analyses were conducted for Trail Making Test B (and other assessments), including interleukin-6 levels, time, and additional confounders (fixed effects), and a random effect for participant. ResultsChanges in interleukin-6 levels were associated with changes in Trail Making Test B over 1 yr in a generalised additive model (β=0.074, P<0.001) supporting that unresolved inflammation impaired executive function. This result was robust to confounders, outlier rejection, and fitting to non-linear models. Changes in interleukin-6 levels also correlated with changes in Trail Making Test A and Controlled Oral Word Association Test. Sensitivity analyses conducted on binary definitions of cognitive decline (>1, >1.5, or >2 standard deviations from baseline) were also associated with interleukin-6 changes. ConclusionsDelayed resolution of inflammation is associated with cognitive impairment after surgery. Monitoring interleukin-6 might provide an opportunity to intervene with anti-inflammatory therapies in vulnerable patients. Clinical trial registrationNCT01980511, NCT03124303.

The association of hypoglycemia with outcome of critically ill children in relation to nutritional and blood glucose control strategies

BackgroundWithholding parenteral nutrition (PN) until one week after PICU admission facilitated recovery from critical illness and protected against emotional and behavioral problems 4 years later. However, the intervention increased the risk of hypoglycemia, which may have counteracted part of the benefit. Previously, hypoglycemia occurring under tight glucose control in critically ill children receiving early PN did not associate with long-term harm. We investigated whether hypoglycemia in PICU differentially associates with outcome in the context of withholding early PN, and whether any potential association with outcome may depend on the applied glucose control protocol.MethodsIn this secondary analysis of the multicenter PEPaNIC RCT, we studied whether hypoglycemia in PICU associated with mortality (N = 1440) and 4-years neurodevelopmental outcome (N = 674) through univariable comparison and multivariable regression analyses adjusting for potential confounders. In patients with available blood samples (N = 556), multivariable models were additionally adjusted for baseline serum NSE and S100B concentrations as biomarkers of neuronal, respectively, astrocytic damage. To study whether an association of hypoglycemia with outcome may be affected by the nutritional strategy or center-specific glucose control protocol, we further adjusted the models for the interaction between hypoglycemia and the randomized nutritional strategy, respectively, treatment center. In sensitivity analyses, we studied whether any association with outcome was different in patients with iatrogenic or spontaneous/recurrent hypoglycemia.ResultsHypoglycemia univariably associated with higher mortality in PICU, at 90 days and 4 years after randomization, but not when adjusted for risk factors. After 4 years, critically ill children with hypoglycemia scored significantly worse for certain parent/caregiver-reported executive functions (working memory, planning and organization, metacognition) than patients without hypoglycemia, also when adjusted for risk factors including baseline NSE and S100B. Further adjustment for the interaction of hypoglycemia with the randomized intervention or treatment center revealed a potential interaction, whereby tight glucose control and withholding early PN may be protective. Impaired executive functions were most pronounced in patients with spontaneous or recurrent hypoglycemia.ConclusionCritically ill children exposed to hypoglycemia in PICU were at higher risk of impaired executive functions after 4 years, especially in cases of spontaneous/recurrent hypoglycemia.

Prefrontal cortex melanocortin 4 receptors (MC4R) mediate food intake behavior in male mice

BackgroundMelanocortin 4 receptor (MC4R) activity in the hypothalamus is crucial for regulation of metabolism and food intake. The peptide ligands for the MC4R are associated with feeding, energy expenditure, and also with complex behaviors that orchestrate energy intake and expenditure, but the downstream neuroanatomical and neurochemical targets associated with these behaviors are elusive. In addition to strong expression in the hypothalamus, the MC4R is highly expressed in the medial prefrontal cortex, a region involved in executive function and decision-making. MethodsUsing viral techniques in genetically modified male mice combined with molecular techniques, we identify and define the effects on feeding behavior of a novel population of MC4R expressing neurons in the infralimbic (IL) region of the cortex. ResultsHere, we describe a novel population of MC4R-expressing neurons in the IL of the mouse prefrontal cortex that are glutamatergic, receive input from melanocortinergic neurons, and project to multiple regions that coordinate appetitive responses to food-related stimuli. The neurons are stimulated by application of MC4R-specific peptidergic agonist, THIQ. Deletion of MC4R from the IL neurons causes increased food intake and body weight gain and impaired executive function in simple food-related behavior tasks. ConclusionTogether, these data suggest that MC4R neurons of the IL play a critical role in the regulation of food intake in male mice.

Association of childhood trauma with cognitive domains in adult patients with mental disorders and in non-clinical populations: a systematic review.

Although the association between cognitive performances and the onset of psychiatric disorders has been widely investigated, limited research on the role of childhood trauma or early life stress (CT/ELS), and whether this role differs between clinical and non-clinical cohorts is available. This systematic review aims at filling this gap, testing whether the occurrence of CT/ELS and its subtypes are associated with cognitive domains (general cognitive ability, executive functions, working memory, attention, processing speed, verbal/visual memory) in patients with psychiatric disorders and in non-clinical populations. This study followed the PRISMA 2020 guidelines and the Newcastle-Ottawa scale for quality assessment. The search was performed until May 2022. Seventy-four studies were classified as eligible. The graphical representations of the results reported an association between exposure to CT/ELS and worse general cognitive ability, verbal/visual memory, processing speed and attention in patients affected by anxiety, mood and psychotic disorders, and that specific CT/ELS subtypes (physical neglect, physical/sexual abuse) can differentially influence specific cognitive abilities (executive functions, attention, working memory, verbal/visual memory). In non-clinical cohorts we found associations between CT/ELS exposure and impairments in executive functions, processing speed and working memory, while physical neglect was related to general cognitive ability and working memory. Concerning the emotional abuse/neglect subtypes in both populations, the results indicated their involvement in cognitive functioning; however, the few studies conducted are not enough to reach definitive conclusions. These findings suggest an association of CT/ELS with specific cognitive deficits and psychopathology.

Executive functions and borderline personality features in adolescents with major depressive disorder.

Executive functions (EF) consolidate during adolescence and are impaired in various emerging psychiatric disorders, such as pediatric Major Depressive Disorder (pMDD) and Borderline Personality Disorder. Previous studies point to a marked heterogeneity of deficits in EF in pMDD. We examined the hypothesis that deficits in EF in adolescents with pMDD might be related to comorbid Borderline Personality features (BPF). We examined a sample of 144 adolescents (15.86 ± 1.32) diagnosed with pMDD. Parents rated their child's EF in everyday life with the Behavior Rating Inventory of Executive Function (BRIEF) and BPF with the Impulsivity and Emotion Dysregulation Scale (IED-27). The adolescents completed equivalent self-rating measures. Self- and parent-ratings of the BRIEF scores were compared with paired t-Tests. Correlation and parallel mediation analyses, ICC, and multiple regression analyses were used to assess symptom overlap, parent-child agreement, and the influence of depression severity. Over the whole sample, none of the self- or parent-rated BRIEF scales reached a mean score above T > 65, which would indicate clinically impaired functioning. Adolescents tended to report higher impairment in EF than their parents. Depression severity was the strongest predictor for BPF scores, with Emotional Control predicting parent-rated BPF and Inhibit predicting self-rated BPF. Furthermore, the Behavioral Regulation Index, which includes EF closely related to behavioral control, significantly mediated the relationship between depression severity and IED-27 factors emotional dysregulation and relationship difficulties but not non-suicidal self-injuries. On average, adolescents with depression show only subtle deficits in executive functioning. However, increased EF deficits are associated with the occurrence of comorbid borderline personality features, contributing to a more severe overall psychopathology. Therefore, training of executive functioning might have a positive effect on psychosocial functioning in severely depressed adolescents, as it might also improve comorbid BPF. www.ClinicalTrials.gov, identifier NCT03167307.

Social cognition and adjustment in adult survivors of pediatric central nervous system tumors.

Survivors of pediatric central nervous system (CNS) tumors are at risk for neurocognitive and social difficulties throughout childhood. This study characterized social cognition (perception and reasoning from social cues) and adjustment in adulthood. A total of 81 adult survivors of pediatric CNS tumors (51% female; mean [SD] age,28.0 [5.8] years), were recruited across four groups: (1) no radiation therapy (RT) [n=21], (2) infratentorial (IT) tumors+focal RT [n=20], (3) IT tumors+craniospinal irradiation [n=20], and (4) supratentorial tumors+focal RT [n=20]. Prevalence of social cognitive and adjustment impairments was compared to test norms. Multivariable models examined clinical and neurocognitive predictors of social cognition and its impact on functional outcomes. Survivors demonstrated elevated risk of severe social cognitive impairments (social perception Morbidity Ratio [95% CI] 5.70 [3.46-9.20]), but self-reported few social adjustment problems. Survivors of IT tumors treated with craniospinal irradiation performed nearly 1 SD worse than survivors treated without RT on multiple measures of social cognition (e.g., social perception: β=-0.89, p=.004). Impaired executive functioning and nonverbal reasoning were associated with worse social cognitive performance (e.g., social perception: β=-0.75, p<.001; β=-0.84, p<.001, respectively). Better social perception was associated with higher odds of attaining full-time employment (odds ratio, 1.52 [1.17-1.97]) and at least some college education (odds ratio, 1.39 [1.11-1.74]). Adult survivors of CNS tumors are at elevated risk of severely impaired social cognition, but do not perceive social adjustment difficulties. Better understanding of potential mechanisms underlying social cognitive deficits may inform intervention targets to promote better functional outcomes for at-risk survivors.

Untreated if unrecognized: A cognitive profile of sustained subjective executive dysfunctions in COVID-19

ABSTRACT & STATEMENT OF IMPACT SARS-COV-2 infection can result in acute and long-lasting cognitive complaints, causing ongoing impairments in daily life which poses a challenge to society. Consequently, the evaluation and characterization of cognitive complaints, specifically in the domain of executive functions (EFs) affecting daily life, is imperative in formulating an effective neuropsychological response. In total 442 participants aged 18–65+ years from the Netherlands, Germany, Mexico, and Spain were included in an online questionnaire. Among others, the questionnaire consisted of demographics, the Behavior Rating Inventory of Executive Functioning for Adults (BRIEF-A), measures of subjective disease progression severity and experienced subjective impairment in daily activities. To assess whether daily life activities are affected by EF impairments, the main BRIEF-A composite score (GEC) was analyzed. To determine whether disease-related COVID-19 factors predict EFs complaints in daily life, a stepwise regression analysis was performed with i) experienced disease severity, ii) time since disease, and iii) health risk factor as predictors. The study revealed noteworthy differences in the occurrence of EFs problems in daily life between both groups, as indicated by the GEC, which exhibited a medium effect size even 6 months post-COVID-19 diagnosis even in mild disease progression. The scores of the BRIEF-A subscales follow a domain-specific profile, and includes clinically relevant impairments in: Working memory, Plan/Organize, Task Monitor, Shift, which are affected by the experienced severity of the disease. This cognitive profile has important implications for targeted cognitive training in rehabilitation and has the potential for an applicability to other viruses as well.

A Cognitive Biotype of Depression and Symptoms, Behavior Measures, Neural Circuits, and Differential Treatment Outcomes

Cognitive deficits in depression have been associated with poor functional capacity, frontal neural circuit dysfunction, and worse response to conventional antidepressants. However, it is not known whether these impairments combine together to identify a specific cognitive subgroup (or "biotype") of individuals with major depressive disorder (MDD), and the extent to which these impairments mediate antidepressant outcomes. To undertake a systematic test of the validity of a proposed cognitive biotype of MDD across neural circuit, symptom, social occupational function, and treatment outcome modalities. This secondary analysis of a randomized clinical trial implemented data-driven clustering in findings from the International Study to Predict Optimized Treatment in Depression, a pragmatic biomarker trial in which patients with MDD were randomized in a 1:1:1 ratio to antidepressant treatment with escitalopram, sertraline, or venlafaxine extended-release and assessed at baseline and 8 weeks on multimodal outcomes between December 1, 2008, and September 30, 2013. Eligible patients were medication-free outpatients with nonpsychotic MDD in at least the moderate range, and were recruited from 17 clinical and academic practices; a subset of these patients underwent functional magnetic resonance imaging. This prespecified secondary analysis was performed between June 10, 2022, and April 21, 2023. Pretreatment and posttreatment behavioral measures of cognitive performance across 9 domains, depression symptoms assessed using 2 standard depression scales, and psychosocial function assessed using the Social and Occupational Functioning Assessment Scale and World Health Organization Quality of Life scale were analyzed. Neural circuit function engaged during a cognitive control task was measured using functional magnetic resonance imaging. A total of 1008 patients (571 [56.6%] female; mean [SD] age, 37.8 [12.6] years) participated in the overall trial and 96 patients participated in the imaging substudy (45 [46.7%] female; mean [SD] age, 34.5 [13.5] years). Cluster analysis identified what may be referred to as a cognitive biotype of 27% of depressed patients with prominent behavioral impairment in executive function and response inhibition domains of cognitive control. This biotype was characterized by a specific profile of pretreatment depressive symptoms, worse psychosocial functioning (d = -0.25; 95% CI, -0.39 to -0.11; P < .001), and reduced activation of the cognitive control circuit (right dorsolateral prefrontal cortex: d = -0.78; 95% CI, -1.28 to -0.27; P = .003). Remission was comparatively lower in the cognitive biotype positive subgroup (73 of 188 [38.8%] vs 250 of 524 [47.7%]; P = .04) and cognitive impairments persisted regardless of symptom change (executive function: ηp2 = 0.241; P < .001; response inhibition: ηp2 = 0.750; P < .001). The extent of symptom and functional change was specifically mediated by change in cognition but not the reverse. Our findings suggest the presence of a cognitive biotype of depression with distinct neural correlates, and a functional clinical profile that responds poorly to standard antidepressants and instead may benefit from therapies specifically targeting cognitive dysfunction. ClinicalTrials.gov Identifier: NCT00693849.

Association of Bilateral Vestibulopathy With and Without Hearing Loss With Cognitive-Motor Interference

The past years, evidence suggested that the primary symptoms traditionally associated with bilateral vestibulopathy (BV) do not represent the full picture of this patient population. Recent literature also demonstrated cognitive impairment. However, although multitasking and dual-tasking are widely present in everyday activities, most of these studies assessed cognitive function only in single-task conditions. To uncover the association of BV with and without hearing loss with cognitive and motor performance and cognitive-motor interference. This prospective case-control study assessed persons with an isolated BV and persons with BV and a concomitant hearing loss compared with a healthy control group. Data were analyzed in December 2022. The study was conducted at Ghent University (Ghent, Belgium). Data collection took place between March 26, 2021, and November 29, 2022. All participants completed the 2BALANCE dual-task protocol, comprising a static and a dynamic motor task that was combined with 5 visual cognitive tasks. These cognitive tasks assessed mental rotation, visuospatial memory, working memory, response inhibition (executive function), and processing speed. All cognitive tasks were performed in a single-task condition (while seated) and in a dual-task condition (combined with a static and a dynamic motor task). The static task comprised balancing on a force platform with foam pad, and the dynamic task comprised walking at a self-selected speed on the GAITRite Walkway. Both motor tasks were performed in the single-task and dual-task condition. Nineteen persons with BV and hearing loss (mean [SD] age, 56.70 [10.12] years; 10 women [52.6%]), 22 persons with an isolated BV (mean [SD] age, 53.66 [13.35] years; 7 women [31.8%]), and 28 healthy control participants were included (mean [SD] age, 53.73 [12.77] years; 12 women [42.9%]). Both patient groups had mental rotation and working memory impairment in a single-task condition and slower processing speed when walking (ie, during the dynamic dual-task condition). Additionally, the patient group with hearing loss had impaired visuospatial memory and executive function deficits in single-task and dual-task conditions, while this could only be elicited when performing a motor task in persons with isolated BV (ie, when dual-tasking). The findings of this case-control study suggest an association between vestibular function and cognitive and motor performance, even greater in persons with a concomitant hearing loss than in persons with an isolated BV.

Long-term improvements in executive functions after frontal-midline theta neurofeedback in a (sub)clinical group.

Impairments in executive functions (EFs) are common across disorders and can greatly affect daily functioning. Frontal-midline (FM) theta neurofeedback (NF) has been shown effective in enhancing EFs in healthy adults, prompting interest in exploring its potential as an alternative treatment for EFs in (sub)clinical samples. This study aims to determine the effects of FM theta NF on EFs in a sample of 58 adults (aged 20-60 years) with pronounced subjective EF complaints in daily life. Using a pre/post/follow-up design with a sham NF group, the present study assessed upregulation of FM theta in an eight-session individualized FM theta NF training and its immediate and long-term transfer effects on objective and subjective measures of EFs. These included behavioral performance on EF tasks assessing working memory updating (N-back task), set-shifting (Switching task), conflict monitoring (Stroop task), and response inhibition (Stop-signal task), as well as FM theta power during these tasks, and subjective EFs in daily life (BRIEF-A). The results indicate that there are only differences in FM theta self-upregulation between the NF group and sham group when non-responders are excluded from the analysis. Regarding behavioral transfer effects, NF-specific improvements are found in working memory updating reaction time (RT) and conflict monitoring RT variability at 6-month follow-up, but not immediately after the NF training. The effects on FM theta power during the EF tasks and subjective changes in EFs in daily life were not specific to the NF training. As a next step, research should identify the best predictors to stratify NF training, as well as explore ways to improve NF responsiveness, for instance by increasing neuroplasticity.

A Neuropsychiatric Assessment of Children with Previous SARS-CoV-2 Infection.

Concerns have been raised about possible neuropsychiatric sequelae of COVID-19. The objective of this study was to examine the plausibility of long-term mental health consequences of COVID-19 by assessing a sample of children after the resolution of the acute SARS-CoV-2 infection. As part of a systematic follow-up assessment of pediatric patients with COVID-19 conducted at two university children's hospitals, 50 children (56% males) aged 8 to 17 years (median 11.5), 26% with previous multisystem inflammatory syndrome in children (MIS-C), without a prior history of neuropsychiatric disorders, received a battery of clinical neuropsychiatric and neuropsychological rating scales that included the Pediatric Migraine Disability Assessment (PedMIDAS), Sleep Disturbance Scale for Children (SDSC), Multidimensional Anxiety Scale for Children (MASC-2), Child Depression Inventory (CDI-2), Child Behavior Checklist (CBCL), and the NEPSY II (Neuropsychological Assessment, Second Edition). The assessments were conducted between 1 and 18 months (median 8 months) after the acute infection. The CBCL internalizing symptoms score was in the clinical range for 40% of the participants (vs. a population expected rate of about 10%, p < 0.001). A sleep disturbance was detected in 28%, clinically significant anxiety in 48%, and depressive symptoms in 16%. The NEPSY II scores showed impairment in attention and other executive functions in 52%, and memory deficits in 40% of the children. These data from direct assessment of a sample of children who had SARS-CoV-2 infection show higher than expected rates of neuropsychiatric symptoms, thus supporting the possibility that COVID-19 may have mental health sequelae long after the resolution of the acute infection.

Genetic Variants, Neurocognitive Outcomes, and Functional Neuroimaging in Survivors of Childhood Acute Lymphoblastic Leukemia.

Genetic predispositions may modulate risk for developing neurocognitive late effects in childhood acute lymphoblastic leukemia (ALL) survivors. Long-term ALL survivors (n = 212; 14.3[4.77] years, mean[SD]; 49% female) treated with chemotherapy completed neurocognitive testing and task-based functional neuroimaging (fMRI). Based on previous work from our team, genetic variants related to the folate pathway, glucocorticoid regulation, drug metabolism, oxidative stress, and attention were included as predictors of neurocognitive performance, using multivariable models adjusted for age, race, and sex. Subsequent analyses evaluated the impact of these variants on task-based fMRI. Statistical tests were two-sided. Survivors exhibited higher rates of impaired attention(20.8%), motor skills(42.2%), visuo-spatial memory(49.3-58.3%), processing speed(20.1%), and executive function(24.3-26.1%) relative to population norms (10%; p's < 0.001). Genetic variants implicated in attention deficit phenotypes predicted impaired attention span (synaptosome associated protein 25 [SNAP25rs3746544], F(2,172)=4.07, p = 0.019) and motor skills (monoamine oxidase A, [MAOArs1137070], F(2,125)=5.25, p = 0.007). Visuo-spatial memory and processing speed varied as a function of genetic variants in the folate pathway (methylenetetrahydrofolate reductase [MTHFRrs1801133], F(2,165)=3.48, p = 0.033; methylenetetrahydrofolate dehydrogenase 1 [MTHFD1rs2236225], F(2,135)=3.8, p = 0.025; respectively). Executive function performance was modulated by genetic variants in the folate pathway (MTHFD1rs2236225, F(2,158)=3.95, p = 0.021; MTHFD1rs1950902, F(2,154)=5.55, p = 0.005) and glucocorticoid regulation (vitamin D receptor [VDRrs154410], F(2,158)=3.29, p = 0.039; FKBP prolyl isomerase 5 [FKBP5rs1360780], F(2,154)=5.6, p = 0.005). Additionally, MTHFD1rs2236225 and FKBP5rs1360780 were associated with altered brain function during attention and working memory (p < 0.05; FWE corrected). Results extend previous findings of genetic risk of neurocognitive impairment following ALL therapy and highlight the importance of examining genetic modulators in relation to neurocognitive deficits.

Impact and centrality of attention dysregulation on cognition, anxiety, and low mood in adolescents

Functional impairments in cognition are frequently thought to be a feature of individuals with depression or anxiety. However, documented impairments are both broad and inconsistent, with little known about when they emerge, whether they are causes or effects of affective symptoms, or whether specific cognitive systems are implicated. Here, we show, in the adolescent ABCD cohort (N = 11,876), that attention dysregulation is a robust factor underlying wide-ranging cognitive task impairments seen in adolescents with moderate to severe anxiety or low mood. We stratified individuals high in DSM-oriented depression or anxiety symptomology, and low in attention deficit hyperactivity disorder (ADHD), as well as vice versa – demonstrating that those high in depression or anxiety dimensions but low in ADHD symptoms not only exhibited normal task performance across several commonly studied cognitive paradigms, but out-performed controls in several domains, as well as in those low in both dimensions. Similarly, we showed that there were no associations between psychopathological dimensions and performance on an extensive cognitive battery after controlling for attention dysregulation. Further, corroborating previous research, the co-occurrence of attention dysregulation was associated with a wide range of other adverse outcomes, psychopathological features, and executive functioning (EF) impairments. To assess how attention dysregulation relates to and generates diverse psychopathology, we performed confirmatory and exploratory network analysis with different analytic approaches using Gaussian Graphical Models and Directed Acyclic Graphs to examine interactions between ADHD, anxiety, low mood, oppositional defiant disorder (ODD), social relationships, and cognition. Confirmatory centrality analysis indicated that features of attention dysregulation were indeed central and robustly connected to a wide range of psychopathological traits across different categories, scales, and time points. Exploratory network analysis indicated potentially important bridging traits and socioenvironmental influences in the relationships between ADHD symptoms and mood/anxiety disorders. Trait perfectionism was uniquely associated with both better cognitive performance and broad psychopathological dimensions. This work suggests that attentional dysregulation may moderate the breadth of EF, fluid, and crystalized cognitive task outcomes seen in adolescents with anxiety and low mood, and may be central to disparate pathological features, and thus a target for attenuating wide-ranging negative developmental outcomes.

A Verbal Card Sorting Task to Measure Executive Functions.

The Wisconsin Card Sorting Test (WCST) is commonly used to measure nonverbal executive functions (EFs) in a variety of clinical populations. However, in some clinical populations (e.g., people with aphasia), deficits may be present in more linguistic (or verbal) domains and less pronounced in nonverbal domains. Thus, when determining possible deficits in these individuals, it is critical to assess both verbal and nonverbal cognitive abilities. The purpose of this study was to create a verbal card sorting task (VCST) to complement the WCST. We created the VCST by modifying a computerized version of the WCST, the Berg Card Sorting Task (BCST). We then compared 35 individuals with mild traumatic brain injury (mTBI) and 33 matched controls' performance on each task. We tested the VCST in individuals with mTBI first because they demonstrate impaired EFs but unimpaired language. We therefore expected the mTBI group to perform similarly on the VCST and BCST, suggesting that the two tasks measure EFs similarly. In line with our hypothesis, the mTBI group had unimpaired inhibition and sustained attention but impaired shifting on each task. Component loadings for both tasks were also similar, and participants' inhibition and shifting scores positively correlated across the two tasks. Together, these findings suggest that the VCST is a potentially useful tool for measuring verbal EF deficits. Our results also provide important insights into the EF impairments experienced by individuals with mTBI. https://doi.org/10.23641/asha.23230475.

Cognitive functioning in postural orthostatic tachycardia syndrome among different body positions: a prospective pilot study (POTSKog study)

PurposeApproximately 96% of patients with postural orthostatic tachycardia syndrome (PoTS) report cognitive complaints. We investigated whether cognitive function is impaired during sitting and active standing in 30 patients with PoTS compared with 30 healthy controls (HCs) and whether it will improve with the counter manoeuvre of leg crossing.MethodsIn this prospective pilot study, patients with PoTS were compared to HCs matched for age, sex, and educational level. Baseline data included norepinephrine plasma levels, autonomic testing and baseline cognitive function in a seated position [the Montreal Cognitive Assessment, the Leistungsprüfsystem (LPS) subtests 1 and 2, and the Test of Attentional Performance (TAP)]. Cognitive functioning was examined in a randomized order in supine, upright and upright legs crossed position. The primary outcomes were the cognitive test scores between HCs and patients with PoTS at baseline testing, and among the different body positions.ResultsPatients with PoTS had impaired attention (TAP median reaction time) in the seated position and impaired executive functioning (Stroop) while standing compared with HC. Stroop was influenced by position (supine versus upright versus upright legs crossed) only in the PoTS group. Leg crossing did not result in an improvement in executive function. In patients with PoTS, there was a negative correlation of Stroop with norepinephrine plasma levels while standing.ConclusionCompared with HCs, PoTS participants showed impaired cognitive attention and executive function in the upright position that did not improve in the legs crossed position. Data provide further evidence for orthostatic cognitive deterioration in patients with PoTS.Trial Registration InformationThe study was registered at ClinicalTrials.gov (NCT03681080).