Showing papers on "Executive dysfunction published in 2018"

Autism spectrum disorders: a meta-analysis of executive function

Abstract: Evidence of executive dysfunction in autism spectrum disorders (ASD) across development remains mixed and establishing its role is critical for guiding diagnosis and intervention. The primary objectives of this meta-analysis is to analyse executive function (EF) performance in ASD, the fractionation across EF subdomains, the clinical utility of EF measures and the influence of multiple moderators (for example, age, gender, diagnosis, measure characteristics). The Embase, Medline and PsychINFO databases were searched to identify peer-reviewed studies published since the inclusion of Autism in DSM-III (1980) up to end of June 2016 that compared EF in ASD with neurotypical controls. A random-effects model was used and moderators were tested using subgroup analysis. The primary outcome measure was Hedges' g effect size for EF and moderator factors. Clinical sensitivity was determined by the overlap percentage statistic (OL%). Results were reported according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 235 studies comprising 14 081 participants were included (N, ASD=6816, Control=7265). A moderate overall effect size for reduced EF (Hedges' g=0.48, 95% confidence interval (CI) 0.43-0.53) was found with similar effect sizes across each domain. The majority of moderator comparisons were not significant although the overall effect of executive dysfunction has gradually reduced since the introduction of ASD. Only a small number of EF measures achieved clinical sensitivity. This study confirms a broad executive dysfunction in ASD that is relatively stable across development. The fractionation of executive dysfunction into individual subdomains was not supported, nor was diagnostic sensitivity. Development of feasible EF measures focussing on clinical sensitivity for diagnosis and treatment studies should be a priority.

Prefrontal cortex executive processes affected by stress in health and disease.

Abstract: Prefrontal cortical executive functions comprise a number of cognitive capabilities necessary for goal directed behavior and adaptation to a changing environment. Executive dysfunction that leads to maladaptive behavior and is a symptom of psychiatric pathology can be instigated or exacerbated by stress. In this review we survey research addressing the impact of stress on executive function, with specific focus on working memory, attention, response inhibition, and cognitive flexibility. We then consider the neurochemical pathways underlying these cognitive capabilities and, where known, how stress alters them. Finally, we review work exploring potential pharmacological and non-pharmacological approaches that can ameliorate deficits in executive function. Both preclinical and clinical literature indicates that chronic stress negatively affects executive function. Although some of the circuitry and neurochemical processes underlying executive function have been characterized, a great deal is still unknown regarding how stress affects these processes. Additional work focusing on this question is needed in order to make progress on developing interventions that ameliorate executive dysfunction.

Diabetes and Cognitive Decline in Older Adults: The Ginkgo Evaluation of Memory Study.

Abstract: Background Previous studies have shown that individuals with diabetes exhibit accelerated cognitive decline. However, methodological limitations have limited the quality of this evidence. Heterogeneity in study design, cognitive test administration, and methods of analysis of cognitive data have made it difficult to synthesize and translate findings to practice. We analyzed longitudinal data from the Ginkgo Evaluation of Memory Study to test our hypothesis that older adults with diabetes have greater test-specific and domain-specific cognitive declines compared to older adults without diabetes. Methods Tests of memory, visuo-spatial construction, language, psychomotor speed, and executive function were administered. Test scores were standardized to z-scores and averaged to yield domain scores. Linear random effects models were used to compare baseline differences and changes over time in test and domain scores among individuals with and without diabetes. Results Among the 3,069 adults, aged 72-96 years, 9.3% reported diabetes. Over a median follow-up of 6.1 years, participants with diabetes exhibited greater baseline differences in a test of executive function (trail making test, Part B) and greater declines in a test of language (phonemic verbal fluency). For the composite cognitive domain scores, participants with diabetes exhibited lower baseline executive function and global cognition domain scores, but no significant differences in the rate of decline. Conclusions Identifying cognitive domains most affected by diabetes can lead to targeted risk modification, possibly in the form of lifestyle interventions such as diet and physical activity, which we know to be beneficial for improving vascular risk factors, such as diabetes, and therefore may reduce the risk of executive dysfunction and possible dementia.

Prevalence of Cognitive Impairment and Association With Survival Among Older Patients With Hematologic Cancers

Abstract: Importance As the population ages, cognitive impairment has promised to become increasingly common among patients with cancer. Little is known about how specific domains of cognitive impairment may be associated with survival among older patients with hematologic cancers. Objective To determine the prevalence of domain-specific cognitive impairment and its association with overall survival among older patients with blood cancer. Design, Setting, and Participants This prospective observational cohort study included all patients 75 years and older who presented for initial consultation in the leukemia, myeloma, or lymphoma clinics of a large tertiary hospital in Boston, Massachusetts, from February 1, 2015, to March 31, 2017. Patients underwent screening for frailty and cognitive dysfunction and were followed up for survival. Exposures The Clock-in-the-Box (CIB) test was used to screen for executive dysfunction. A 5-word delayed recall test was used to screen for impairment in working memory. The Fried frailty phenotype and Rockwood cumulative deficit model of frailty were also assessed to characterize participants as robust, prefrail, or frail. Results Among 420 consecutive patients approached, 360 (85.7%) agreed to undergo frailty assessment (232 men [64.4%] and 128 women [35.6%]; mean [SD] age, 79.8 [3.9] years), and 341 of those (94.7%) completed both cognitive screening tests. One hundred twenty-seven patients (35.3%) had probable executive dysfunction on the CIB, and 62 (17.2%) had probable impairment in working memory on the 5-word delayed recall. Impairment in either domain was modestly correlated with the Fried frailty phenotype (CIB, ρ = 0.177; delayed recall, ρ = 0.170;P = .01 for both), and many phenotypically robust patients also had probable cognitive impairment (24 of 104 [23.1%] on CIB and 9 of 104 [8.7%] on delayed recall). Patients with impaired working memory had worse median survival (10.9 [SD, 12.9] vs 12.2 [SD, 14.7] months; log-rankP Conclusions and Relevance These data suggest that domains of cognitive dysfunction may be prevalent in older patients with blood cancer and may have differential predictive value for survival. Targeted interventions are needed for this vulnerable patient population.

Trends in Executive Functioning in Extremely Preterm Children Across 3 Birth Eras.

Abstract: BACKGROUND AND OBJECTIVES: To determine if executive functioning outcomes at school age are different for extremely preterm (EP; METHODS: Population-based cohorts of all EP/ELBW survivors born in the state of Victoria, Australia, in 1991 to 1992, 1997, and 2005, and contemporaneous controls (matched for expected date of birth, sex, mother’s country of birth [English speaking or not], and health insurance status) were recruited at birth. At 7 to 8 years of age, parents of 613 children who were EP/ELBW and 564 children who were controls rated their children’s executive functioning on the Behavior Rating Inventory of Executive Function (BRIEF). The proportion of children with elevated BRIEF scores (in the clinically significant range) in each birth group and era was compared by using logistic regression. Sensitivity analyses explored these associations after excluding children with intellectual impairment. RESULTS: Across the eras, EP/ELBW children had higher rates of elevated scores than controls in almost all BRIEF domains. The 2005 EP/ELBW cohort had increased executive dysfunction compared with earlier cohorts, particularly in working memory and planning and organization. This effect persisted after accounting for demographic factors and weakened slightly when those with intellectual impairment were excluded. CONCLUSIONS: These results indicate a concerning trend of increasing executive dysfunction for EP/ELBW children who were born more recently. This may have adverse implications for other functional domains, such as academic achievement and social-emotional well-being.

HIV-associated executive dysfunction in the era of modern antiretroviral therapy: A systematic review and meta-analysis.

Abstract: Objective: While some reports suggest that HIV+ individuals continue to display executive function (EF) impairment in the era of cART, findings have been contradictory and appear to differ based on the aspect of EF being measured. To improve the understanding of how discrete executive abilities may be differentially affected or spared in the context of HIV infection, we conducted a systematic review and meta-analysis to (a) determine whether and to what extent HIV+ adults experience deficits in EFs, and (b) understand how demographic and clinical characteristics may modify the associations between HIV infection and executive abilities.Method: Studies comparing HIV+ and HIV-uninfected groups on measures of working memory, set-shifting, inhibition, decision-making, and apathy between 2000 and 2017 were identified from three databases. Effect sizes (Cohen’s d) were calculated using inverse variance weighted random effects models. Meta-regression was used to examine the moderating effect of demographi...

Cognitive training for freezing of gait in Parkinson’s disease: a randomized controlled trial

Abstract: The pathophysiological mechanism of freezing of gait (FoG) has been linked to executive dysfunction. Cognitive training (CT) is a non-pharmacological intervention which has been shown to improve executive functioning in Parkinson's disease (PD). This study aimed to explore whether targeted CT can reduce the severity of FoG in PD. Patients with PD who self-reported FoG and were free from dementia were randomly allocated to receive either a CT intervention or an active control. Both groups were clinician-facilitated and conducted twice-weekly for seven weeks. The primary outcome was percentage of time spent frozen during a Timed Up and Go task, assessed both on and off dopaminergic medications. Secondary outcomes included multiple neuropsychological and psychosocial measures. A full analysis was first conducted on all participants randomized, followed by a sample of interest including only those who had objective FoG at baseline, and completed the intervention. Sixty-five patients were randomized into the study. The sample of interest included 20 in the CT group and 18 in the active control group. The primary outcome of percentage time spent frozen during a gait task was significantly improved in the CT group compared to active controls in the on-state. There were no differences in the off-state. Patients who received CT also demonstrated improved processing speed and reduced daytime sleepiness compared to those in the active control. The findings suggest that CT can reduce the severity of FoG in the on-state, however replication in a larger sample is required.

Metacognitive Aspects of Executive Function Are Highly Associated with Social Functioning on Parent-Rated Measures in Children with Autism Spectrum Disorder

Abstract: Autism Spectrum Disorder (ASD) is characterized by social dysfunction. Even though executive dysfunction has been recognized as important in understanding ASD, the findings are inconsistent. This might be due to different definitions of executive function (EF), which part of EF that has been studied, structured vs. unstructured tasks, inclusion of different moderators (age, IQ, sex) and different diagnostic categories within the spectrum. The main finding is that people with ASD have more EF difficulties than normal controls and more difficulties on open-end tasks than on structured cognitive tasks. Since some EF difficulties may not be observable in a laboratory setting, informant measures might have higher ecological validity than neuropsychological tests. Evidence suggests that executive dysfunctions are associated with social impairments, but few studies have investigated the details of this relationship, and it remains unclear what types of EF deficits are relevant for the social problems of individuals with ASD. Here we investigated which EF domains were associated with various domains of social function on parent-rated measures. A total of 86 children and adolescents with a diagnosis of ASD were included and tested for general cognitive abilities. Parents completed the Behavior Rating Inventory of Executive Function (BRIEF) and the Social Responsiveness Scale (SRS). Multiple regression analysis revealed significant associations between SRS scores and age, sex, total IQ and the BRIEF indexes. The Metacognition Index from the BRIEF added significantly to the prediction of the SRS total score and the subscales Social Communication, Social Motivation and Autistic Mannerisms. The findings suggest that metacognitive aspects of EF are of particular importance for social abilities in children and adolescents with ASD. Earlier research has shown that typically developing (TD) children have a different relationship between EF and social function than children with ASD. They found that in TD children the EF domain related to behavioral regulation was most important to social function. The results from the current study may have implications for understanding the cognitive components of the social problems that define ASD, and may be relevant in developing more targeted clinical EF interventions related to core ASD dysfunctions.

Apathy: a neurocircuitry model based on frontotemporal dementia

Abstract: Apathy is a symptom shared among many neurological and psychiatric disorders. However, the underlying neurocircuitry remains incompletely understood. Apathy is one of the core features of behavioural variant frontotemporal dementia (bvFTD), a neurodegenerative disease presenting with heterogeneous combinations of socioaffective symptoms and executive dysfunction. We reviewed all neuroimaging studies of apathy in frontotemporal dementia (FTD) attempting to refine a neurocircuitry model and inform clinical definitions. Levels of apathy have been consistently shown to correlate with the severity of executive dysfunctions across a wide range of diseases, including FTD. Some authors view ‘energisation’—the loss of which is central in apathy—as a core executive function. Apathy in FTD is most robustly associated with atrophy, hypometabolism and/or hypoperfusion in the dorsolateral prefrontal cortex, the anterior and middle cingulate cortex, the orbitofrontal cortex and the medial and ventromedial superior frontal gyri. Data also suggest that abnormalities in connecting white matter pathways and functionally connected more posterior cortical areas could contribute to apathy. There is a lack of consistency across studies due to small samples, lenient statistical thresholds, variable measurement scales and the focus on apathy as a unitary concept. Integrating findings across studies, we revise a neurocircuitry model of apathy divided along three subcomponents (cognition/planning, initiation, emotional-affective/motivation) with specific neuroanatomical and cognitive substrates. To increase consistency in clinical practice, a recommendation is made to modify the bvFTD diagnostic criteria of apathy/inertia. More generally, we argue that bvFTD constitutes a disease model to study the neurocircuitry of complex behaviours as a ‘lesion-based’ approach to neuropsychiatric symptoms observed across diagnostic categories.

Altered caudate connectivity is associated with executive dysfunction after traumatic brain injury.

Abstract: Traumatic brain injury often produces executive dysfunction. This characteristic cognitive impairment often causes long-term problems with behaviour and personality. Frontal lobe injuries are associated with executive dysfunction, but it is unclear how these injuries relate to corticostriatal interactions that are known to play an important role in behavioural control. We hypothesized that executive dysfunction after traumatic brain injury would be associated with abnormal corticostriatal interactions, a question that has not previously been investigated. We used structural and functional MRI measures of connectivity to investigate this. Corticostriatal functional connectivity in healthy individuals was initially defined using a data-driven approach. A constrained independent component analysis approach was applied in 100 healthy adult dataset from the Human Connectome Project. Diffusion tractography was also performed to generate white matter tracts. The output of this analysis was used to compare corticostriatal functional connectivity and structural integrity between groups of 42 patients with traumatic brain injury and 21 age-matched controls. Subdivisions of the caudate and putamen had distinct patterns of functional connectivity. Traumatic brain injury patients showed disruption to functional connectivity between the caudate and a distributed set of cortical regions, including the anterior cingulate cortex. Cognitive impairments in the patients were mainly seen in processing speed and executive function, as well as increased levels of apathy and fatigue. Abnormalities of caudate functional connectivity correlated with these cognitive impairments, with reductions in right caudate connectivity associated with increased executive dysfunction, information processing speed and memory impairment. Structural connectivity, measured using diffusion tensor imaging between the caudate and anterior cingulate cortex was impaired and this also correlated with measures of executive dysfunction. We show for the first time that altered subcortical connectivity is associated with large-scale network disruption in traumatic brain injury and that this disruption is related to the cognitive impairments seen in these patients.

The contribution of executive control to semantic cognition: Convergent evidence from semantic aphasia and executive dysfunction.

Abstract: Semantic cognition, as described by the controlled semantic cognition (CSC) framework (Rogers et al., , Neuropsychologia, 76, 220), involves two key components: activation of coherent, generalizable concepts within a heteromodal 'hub' in combination with modality-specific features (spokes), and a constraining mechanism that manipulates and gates this knowledge to generate time- and task-appropriate behaviour. Executive-semantic goal representations, largely supported by executive regions such as frontal and parietal cortex, are thought to allow the generation of non-dominant aspects of knowledge when these are appropriate for the task or context. Semantic aphasia (SA) patients have executive-semantic deficits, and these are correlated with general executive impairment. If the CSC proposal is correct, patients with executive impairment should not only exhibit impaired semantic cognition, but should also show characteristics that align with those observed in SA. This possibility remains largely untested, as patients selected on the basis that they show executive impairment (i.e., with 'dysexecutive syndrome') have not been extensively tested on tasks tapping semantic control and have not been previously compared with SA cases. We explored conceptual processing in 12 patients showing symptoms consistent with dysexecutive syndrome (DYS) and 24 SA patients, using a range of multimodal semantic assessments which manipulated control demands. Patients with executive impairments, despite not being selected to show semantic impairments, nevertheless showed parallel patterns to SA cases. They showed strong effects of distractor strength, cues and miscues, and probe-target distance, plus minimal effects of word frequency on comprehension (unlike semantic dementia patients with degradation of conceptual knowledge). This supports a component process account of semantic cognition in which retrieval is shaped by control processes, and confirms that deficits in SA patients reflect difficulty controlling semantic retrieval.

A Systematic Review of Cognition in Chiari I Malformation

Abstract: Displacement of the cerebellar tonsils in Chiari type I malformation (CMI) can affect functions controlled by the cerebellum and brainstem. While playing an integral role in the control of movement, the cerebellum also has widespread cortical connections, influencing a range of cognitive process. A systematic literature review was conducted to examine the relationship between cognition and CMI, assessing evidence for general or domain-specific cognitive change. The search protocol examined the AMED, CINAHL, Cochrane Library, EMBASE, MEDLINE, PsycINFO, and Scopus databases. Articles meeting the following criteria were included in this review (i) examined children or adults with a clinically defined diagnosis of CMI, (ii) assessed cognitive function with a prospective examination, (iii) included at least one standardized instrument designed to measure general or specific domains of cognitive function, and (iv) were published in English in a peer-reviewed journal. Twelve articles were identified, including 783 cases aged 3 months to 64 years. General cognition, processing speed, and learning and memory appeared less affected, while language deficits appeared to diminish with age. Executive dysfunction was the most commonly reported cognitive impairment, while attention and working memory, and visuospatial and perceptual skills also appeared vulnerable. Numerous methodological limitations were identified that should be considered in interpreting the impact of CMI and planning future investigations. Overall, there is currently insufficient evidence to describe a valid and reliable profile of cognitive impairment in CMI. Further research is required to confirm these preliminary psychometric results and integrate them with pathophysiological models

Step length predicts executive dysfunction in Parkinson’s disease: a 3-year prospective study

Abstract: Cognition and gait appear to be closely related. The chronological interplay between cognitive decline and gait dysfunction is not fully understood. The aim of the present prospective study is investigating whether the dysfunction of specific gait parameters, during specific task and medication conditions, may predict subsequent cognitive impairment in Parkinson’s disease (PD). We evaluated cognition and gait in 39 Parkinsonian patients at an initial assessment and after 3 years. Cognitive performance was evaluated with a neuropsychological battery designed to assess memory, executive/attention, and visuospatial domains. Gait was investigated using a gait analysis system during both the off and on states in the following conditions: (1) normal gait; (2) motor dual task; and (3) cognitive dual task. We used regression models to determine whether gait predicts subsequent cognitive dysfunction. Overall, the cognitive test scores were stable over time with the exception of the executive/attention scores, whereas all gait parameters declined. The step length during the cognitive dual task during the on state at the initial evaluation was the only significant predictor of executive/attention domain dysfunction at follow up. The results were confirmed when executive/attention dysfunction at the initial assessment evaluation was included in the regression model as a covariate. Our longitudinal study offers additional insight into the progression of gait dysfunction, and its chronological relationship with cognitive dysfunction in PD patients. In particular, the present study indicates that step length during a cognitive task when on medication is an independent predictor of future executive/attention decline.

The Mechanism of Cortico-Striato-Thalamo-Cortical Neurocircuitry in Response Inhibition and Emotional Responding in Attention Deficit Hyperactivity Disorder with Comorbid Disruptive Behavior Disorder.

Abstract: The neurocircuitries that constitute the cortico-striato-thalamo-cortical (CSTC) circuit provide a framework for bridging gaps between neuroscience and executive function in attention deficit hyperactivity disorder (ADHD), but it has been difficult to identify the mechanisms for regulating emotional problems from the understanding of ADHD comorbidity with disruptive behavior disorders (DBD). Research based on “cool” and “hot” executive functional theory and the dual pathway models, which are thought of as applied response inhibition and delay aversion, respectively, within the neuropsychological view of ADHD, has shed light on emotional responding before and after decontextualized stimuli, while CSTC circuit-related domains have been suggested to explain the different emotional symptoms of ADHD with or without comorbid DBD. This review discusses the role of abnormal connections in each CSTC circuit, especially in the emotion circuit, which may be responsible for targeted executive dysfunction at the neuroscience level. Thus, the two major domains – abstract thinking (cool) and emotional trait (hot) – trigger the mechanism of onset of ADHD.

Neurocognitive and behavioral predictors of social problems in ADHD: A Bayesian framework.

Abstract: Objective Social problems are a key area of functional impairment for children with ADHD, and converging evidence points to executive dysfunction as a potential mechanism underlying ADHD-related social dysfunction. The evidence is mixed, however, with regard to which neurocognitive abilities account for these relations.

A Modified Reading the Mind in the Eyes Test Predicts Behavioral Variant Frontotemporal Dementia Better Than Executive Function Tests.

Abstract: Behavioral variant frontotemporal dementia (bvFTD) is characterized by deep alterations in behavior and personality. Although revised diagnostic criteria agree for executive dysfunction as most characteristic, impairments in social cognition are also suggested. The study aimed at identifying those neuropsychological and behavioral parameters best discriminating between bvFTD and healthy controls. Eighty six patients were diagnosed with possible or probable bvFTD according to Rascovsky et al. (2011) and compared with 43 healthy age-matched controls. Neuropsychological performance was assessed with a modified Reading the Mind in the Eyes Test (RMET), Stroop task, Trail Making Test (TMT), Hamasch-Five-Point Test (H5PT), and semantic and phonemic verbal fluency tasks. Behavior was assessed with the Apathy Evaluation Scale, Frontal Systems Behavioral Scale, and Bayer Activities of Daily Living Scale. Each test's discriminatory power was investigated by Receiver Operating Characteristic curves calculating the area under the curve (AUC). bvFTD patients performed significantly worse than healthy controls in all neuropsychological tests. Discriminatory power (AUC) was highest in behavioral questionnaires, high in verbal fluency tasks and the RMET, and lower in executive function tests such as the Stroop task, TMT and H5PT. As fluency tasks depend on several cognitive functions, not only executive functions, results suggest that the RMET discriminated better between bvFTD and control subjects than other executive tests. Social cognition should be incorporated into diagnostic criteria for bvFTD in the future, such as in the International Classification of Diseases (ICD)-11, as already suggested in the Diagnostic and Statistical Manual for Mental Disorders (DSM)-5.

Systematic Review and Meta-analysis of Executive Functions in Preschool and School-Age Children With Neurofibromatosis Type 1.

Abstract: Objectives Neurofibromatosis type 1 (NF1) is a genetic disorder in which the most frequent complication in children is learning disabilities. Over the past decade, growing arguments support the idea that executive dysfunction is a core deficit in children with NF1. However, some data remain inconsistent. The aim of this study was to determine the magnitude of impairment for each executive function (EF) and clarify the impact of methodological choices and participant's characteristics on EFs. Methods In this meta-analysis, 19 studies met the selection criteria and were included with data from a total of 805 children with NF1 and 667 controls. Based on the Diamond's model (2013), EF measures were coded separately according to the following EF components: working memory, inhibitory control, cognitive flexibility, planning/problem solving. The review protocol was registered with PROSPERO (International prospective register of systematic reviews; CRD42017068808). Results A significant executive dysfunction in children with NF1 is demonstrated. Subgroup analysis showed that the impairment varied as a function of the specific component of executive functioning. The effect size for working memory and planning/problem solving was moderate whereas it was small for inhibitory control and cognitive flexibility. Executive dysfunction seems to be greater with increasing age whereas assessment tool type, intellectual performance, attention deficit hyperactivity disorder and control group composition did not seem to affect EF results. Conclusions EF deficits are a core feature in children with NF1 and an early identification of executive dysfunctions is essential to limit their impact on the quality of life. (JINS, 2018, 24, 977-994).

The effects of post-traumatic depression on cognition, pain, fatigue, and headache after moderate-to-severe traumatic brain injury: a thematic review

Abstract: Background: Post-traumatic depression (PTD) is one of the most common secondary complications to develop after moderate-to-severe traumatic brain injury (TBI). However, it rarely manifests ...

Evolution of neurocognitive function in long-term survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only.

Abstract: The purpose of this study was to determine the evolution of neurocognitive problems from therapy completion to long-term follow-up in survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only. We evaluated whether attention problems observed at therapy completion evolve into long-term executive dysfunction in 158 survivors treated on a single institution protocol. Treatment data (high-dose intravenous methotrexate exposure [serum concentration] and triple intrathecal chemotherapy injections) were collected. Parent report of behavior and direct cognitive testing of survivors was conducted at end of therapy, and survivors completed neurocognitive testing when > 5 years post-diagnosis. At the end of chemotherapy, survivors (52% female; mean age 9.2 years) demonstrated higher frequency of impairment in sustained attention (38%) and parent-reported inattention (20%) compared to population expectations (10%). At long-term follow-up, survivors (mean age 13.7 years; 7.6 years post-diagnosis) demonstrated higher impairment in executive function (flexibility 24%, fluency 21%), sustained attention (15%), and processing speed (15%). Sustained attention improved from end of therapy to long-term follow-up (p 0.05). The direct effect of chemotherapy exposure predicted outcomes at both time points. Survivors should be monitored for neurocognitive problems well into long-term survivorship, regardless of whether they show attention problems at the end of therapy. Treatment exposures are the best predictor of long-term complications.

Executive (dys)Function after Stroke: Special Considerations for Behavioral Pharmacology

Abstract: Stroke is a worldwide leading cause of death and long-term disability with concurrent secondary consequences that are largely comprised of mood dysfunction, as well as sensory, motor, and cognitive deficits. This review focuses on the cognitive deficits associated with stroke specific to executive dysfunction (including decision making, working memory, and cognitive flexibility) in humans, nonhuman primates, and additional animal models. Further, we review some of the cellular and molecular underpinnings of the individual components of executive dysfunction and their neuroanatomical substrates after stroke, with an emphasis on the changes that occur during biogenic monoamine neurotransmission. We concentrate primarily on changes in the catecholaminergic (dopaminergic and noradrenergic) and serotonergic systems at the levels of neurotransmitter synthesis, distribution, reuptake, and degradation. We also discuss potential secondary stroke-related behavioral deficits (specifically, poststroke depression as well as drug-abuse potential and addiction) and their relationship with stroke-induced deficits in executive function, an especially important consideration given that the average age of the human stroke population is decreasing. In the final sections, we address pharmacological considerations for the treatment of ischemia and the subsequent functional impairment, as well as current limitations in the field of stroke and executive function research.

Alterations of the default mode network and cognitive impairment in patients with unilateral chronic tinnitus.

Abstract: Background Previous studies have demonstrated that cognitive impairment is linked with neurophysiological alterations in chronic tinnitus. This study aimed to investigate the intrinsic functional connectivity (FC) pattern within the default mode network (DMN) and its associations with cognitive impairment in tinnitus patients using a resting-state functional magnetic resonance imaging (rs-fMRI). Methods Thirty-five chronic unilateral tinnitus patients, and 50 healthy controls were recruited for rsfMRI scanning. Both groups were age, gender and education level well-matched. The posterior cingulate cortex (PCC) was chosen as the region of interest (ROI) for detecting the FC changes, and determining if these abnormalities were related to a specific cognitive performance and tinnitus characteristic. Results Relative to the healthy controls, tinnitus patients showed increased FC between the PCC and the right medial prefrontal cortex (mPFC). Moreover, the enhanced FC between the PCC and right mPFC was correlated with the poorer TMT-B scores (r=0.474, P=0.008). These correlations were adjusted by age, gender, education level, GM volume, and mean hearing thresholds. The enhanced FC was not correlated with other tinnitus characteristics or cognitive performances. Conclusions The enhanced FC pattern of the PCC that is correlated with cognitive impairment in chronic tinnitus patients, especially the executive dysfunction. Enhanced connectivity pattern within the DMN may play a crucial role in neurophysiological mechanism in tinnitus patients with cognitive dysfunction.

Reduced Short-Latency Afferent Inhibition in Prefrontal but not Motor Cortex and Its Association With Executive Function in Schizophrenia: A Combined TMS-EEG Study.

Abstract: BACKGROUND Cholinergic dysfunction is increasingly assumed to be involved in the pathophysiology of schizophrenia. Short-latency afferent inhibition (SAI) is a transcranial magnetic stimulation (TMS) paradigm that has been shown to assay central cholinergic activity from the motor cortex (M1). Recently, we established a method to index SAI from the dorsolateral prefrontal cortex (DLPFC), an area implicated in the pathophysiology of schizophrenia. We investigated SAI in M1 and DLPFC in schizophrenia. We hypothesized that modulation of N100 on TMS-evoked potentials (TEPs) from the DLPFC would be attenuated in patients with schizophrenia compared to healthy controls. METHODS SAI was examined in 12 patients, whose age was matched to controls, using TMS combined with electroencephalography (EEG). SAI was recorded with TMS applied to left M1 (M1-SAI) and DLPFC (DLPFC-SAI). For group comparison, we used the SAI data of healthy participants in our previous study. RESULTS In patients, N100 TEP was significantly attenuated with DLPFC-SAI, whereas P180 TEP was significantly increased with M1-SAI. Between patients and controls, there were significant differences in modulation of P180 TEP by M1-SAI (t22 = -2.748, P = .012; patients > controls) and N100 TEP by DLPFC-SAI (t22 = 5.456, P < .0001; patients < controls). Further, modulation of N100 TEP by DLPFC-SAI significantly correlated with executive function (r = -.740, P = .006, N = 12). CONCLUSION Our findings suggest that DLPFC-SAI but not M1-SAI were reduced in patients with schizophrenia and this was linked to deficits in cognition. This may reflect prefrontal cholinergic deficits and represent a biomarker for cholinergic and executive dysfunction in patients with schizophrenia.

Executive Functioning Mediates the Relationship Between Pain Coping and Quality of Life in Youth With Sickle Cell Disease.

Abstract: Objective Sickle cell disease (SCD) is a lifelong condition characterized by pain, which is associated with reduced health-related quality of life (HRQL). Data suggest that patients with SCD vary in how they cope and their neurocognitive abilities. This study aimed to characterize executive functioning and pain coping styles in children with SCD experiencing a range of pain frequency (i.e., chronic, episodic, and asymptomatic) and to examine whether executive functioning mediates the relationship between pain coping and HRQL. Method Participants included 100 children and adolescents with SCD between the ages of 8 and 18 years (M = 13.53, SD = 2.8) and their parents who were recruited during outpatient SCD clinic visits in a children's hospital. Children completed questionnaires related to pain experience and pain coping. Parents completed questionnaires about demographic information, their child's executive functioning, and HRQL. Results Pain intensity, executive dysfunction, and engagement in emotion-focused coping (i.e., internalizing/catastrophizing and externalizing) predicted poor HRQL. In addition, engagement in emotion-focused coping predicted executive dysfunction. Multivariate analysis of covariance revealed executive functioning did not differ based on pain frequency; however, executive functioning was a significant mediator that helped explain the relationships between distraction and emotion-focused coping techniques on HRQL. Conclusion Findings support that executive functioning is an important factor in understanding the relationship between pain coping and HRQL in youth with SCD. Future research is warranted to examine the potential impact of executive functioning on the utility of interventions targeting adaptive pain coping in youth with SCD.

Executive function impairments in fibromyalgia syndrome: Relevance of clinical variables and body mass index.

Abstract: Background Several investigations suggest the presence of deterioration of executive function in fibromyalgia syndrome (FMS). The study quantified executive functions in patients with FMS. A wide array of functions was assessed, including updating, shifting and inhibition, as well as decision making and mental planning. Moreover, clinical variables were investigated as possible mediators of executive dysfunction, including pain severity, psychiatric comorbidity, medication and body mass index (BMI). Methods Fifty-two FMS patients and 32 healthy controls completed a battery of 14 neuropsychological tests. Clinical interviews were conducted and the McGill Pain Questionnaire, Beck Depression Inventory, State-Trait Anxiety Inventory, Fatigue Severity Scale and Oviedo Quality of Sleep Questionnaire were presented. Results Patients performed poorer than controls on the Letter Number Sequencing, Arithmetic and Similarities subtests of the Wechsler Adult Intelligence Scale, the Spatial Span subtest of the Wechsler Memory Scale, an N-back task, a verbal fluency task, the Ruff Figural Fluency Test, the Inhibition score of the Stroop Test, the Inhibition and Shifting scores of the Five Digits Test, the Key Search Test and the Zoo Map Task. Moreover, patients exhibited less steep learning curves on the Iowa Gambling Task. Among clinical variables, BMI and pain severity explained the largest proportion of performance variance. Conclusions This study demonstrated impairments in executive functions of updating, shifting inhibition, decision making and planning in FMS. While the mediating role of pain in cognitive impairments in FMS had been previously established, the influence of BMI is a novel finding. Overweight and obesity should be considered by FMS researchers, and in the treatment of the condition.