Neurocognitive Difficulties Research Articles

Efficacy of Neurocognitive Remediation Therapy During an Acute Depressive Episode and Following Remission: Results From Two Randomised Pilot Studies

Introduction Major depression is the most prevalent psychiatric disorder with high relapse rates. Following usual treatment, mood may improve but neurocognitive difficulties often persist, preventing full return to normal social function. These deficits worsen with repeated depressive episodes and are a significant predictor of relapse. The efficacy of neurocognitive remediation therapy (NCRT) to rehabilitate cognition has been demonstrated in several neurological and psychiatric populations but randomised controlled trials (RCT) have not been conducted in depression. Objective Conduct two randomised controlled pilot studies to determine the feasibility and obtain preliminary efficacy data of NCRT in (1) acutely depressed, hospitalised patients; and (2) community-living remitters from recurrent depression. Methods In Pilot1, 24 inpatients hospitalised for major depression were randomised to computerised NCRT or playing computer games for five weeks with four one-hour individual sessions weekly. NCRT targeted divided attention, working memory and planning. In Pilot2, 20 community-living remitters from recurrent depression were randomised to the same intervention arms, but their administration was home-based from the programme start. In both studies, before the intervention start and within a week of the final session, standardised assessments of cognition and depression severity were conducted. Results The feasibility assessment demonstrated good recruitment and compliance rates, excellent acceptance of randomisation. Preliminary outcome data showed improvement in 80% of the targeted cognitive domains following NCRT comparatively to the control condition. Conclusions These pilot studies support the feasibility and value of conducting an RCT of computerised NCRT for neurocognitive deficits in both acutely depressed and remitted individuals.

A Cross Cultural Comparison of Disability and Symptomatology Associated with CFS.

Few studies have compared symptomatology and functional differences experienced by patients with chronic fatigue syndrome (CFS) across cultures. The current study compared patients with CFS from the United States (US) to those from the United Kingdom (UK) across areas of functioning, symptomatology, and illness onset characteristics. Individuals in each sample met criteria for CFS as defined by Fukuda et al. (1994). These samples were compared on two measures of disability and impairment, the DePaul Symptom Questionnarie (DSQ) and the Medical outcomes study 36-item short-form health survey (SF-36). Results revealed that the UK sample was significantly more impaired in terms of mental health and role emotional functioning, as well as specific symptoms of pain, neurocognitive difficulties, and immune manifestations. In addition, the UK sample was more likely to be working rather than on disability. Individuals in the US sample reported more difficulties falling asleep, more frequently reported experiencing a sudden illness onset (within 24 hours), and more often reported that the cause of illness was primarily due to physical causes. These findings suggest that there may be important differences in illness characteristics across individuals with CFS in the US and the UK, and this has implications for the comparability of research findings across these two countries.

Vitamin D in fetal development: findings from a birth cohort study.

Birth cohort studies provide an invaluable resource for studies of the influence of the fetal environment on health in later life. It is uncertain to what extent maternal vitamin D status influences fetal development. Using an unselected community-based cohort of 901 mother-offspring pairs (the Western Australian Pregnancy Cohort [Raine] Study), we examined the relationship between maternal vitamin D deficiency at 18 weeks' pregnancy and long-term health outcomes of offspring who were born in Perth, Western Australia (32° South), in 1989-1991. Vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] <50 nmol/L) was present in 36% (323 of 901) of the pregnant women. After adjusting for relevant covariates, maternal vitamin D deficiency during pregnancy was associated with impaired lung development in 6-year-old offspring, neurocognitive difficulties at age 10, increased risk of eating disorders in adolescence, and lower peak bone mass at 20 years. In summary, vitamin D may have an important, multifaceted role in the development of fetal lungs, brain, and bone. Experimental animal studies support an active contribution of vitamin D to organ development. Randomized controlled trials of vitamin D supplementation in pregnant women with long-term follow-up of offspring are urgently required to examine whether the correction of vitamin D deficiency in pregnant women is beneficial for their offspring and to determine the optimal level of maternal serum 25(OH)D for fetal development.

A population-based prospective birth cohort study of childhood neurocognitive and psychological functioning in healthy survivors of early life meningitis

PurposeTo determine neurocognitive, educational, and psychological functioning during childhood and early adolescence among survivors of early life meningitis who are apparently healthy. MethodsIn the general population-based Avon Longitudinal Study of Parents and Children birth cohort, meningitis exposure was determined at age of 18 months. The outcomes of intelligence quotient, short-term memory, working memory, reading and spelling abilities, psychological and behavioral problems, depressive and anxiety symptoms, and psychotic experiences at ages 9 to 13 years were compared between those exposed and unexposed to meningitis. Individuals with special educational needs were excluded. ResultsBy age of 18 months, 67 of 11,035 children were reported to have suffered from meningitis (0.61%). These children, compared with the unexposed, performed worse on all neurocognitive and educational measures; mean difference in total intelligence quotient 7.36 (95% confidence interval, 1.60–13.11). Meningitis was associated with higher depressive and anxiety symptoms (P = .02), psychological and behavioral problems (P = .09), and increased risk of psychotic experiences; risk ratio 2.22 (95% confidence interval, 1.12–4.38). ConclusionsExposure to meningitis in the early life is associated with neurocognitive, educational, and psychological difficulties during childhood and early adolescence among survivors who are apparently healthy. Therefore, focusing only on serious neurologic disabilities may underestimate the true impact of early life meningitis.

Episodic foresight deficits in long-term opiate users.

There is considerable literature showing that opiate use is associated with a range of neurocognitive deficits, including deficits in executive control and episodic memory. However, no study to date has assessed whether these neurocognitive difficulties extend to the ability to mentally time travel into one's personal future. This is a surprising omission given that executive control and episodic memory are considered to be critical for episodic foresight. In addition, opiate-related brain changes have been identified in the neural regions that underlie the capacity for episodic foresight. In the present study, we assessed how episodic foresight is affected in the context of chronic opiate use, as well as the degree to which any deficits are related to difficulties with executive control and episodic memory. Forty-eight long-term heroin users enrolled in an opiate substitution program and 48 controls were tested. The results showed that, relative to controls, the clinical group exhibited significant impairment in episodic foresight but not episodic memory (as indexed by an adapted version of the Autobiographical Interview). For executive function, the clinical group was impaired on only one of three measures (Inhibition). These data provide important preliminary evidence that episodic foresight might be particularly susceptible to the neurocognitive effects of opiate use, as the difficulties identified were not secondary to more general executive control or episodic memory impairment. Because a number of widely used relapse prevention protocols require the ability to mentally project into the future, these data have potentially important practical implications in relation to the treatment of substance dependence disorders.

Neurocognitive abilities in the general population and composite genetic risk scores for attention-deficit hyperactivity disorder.

BackgroundThe genetic architecture of ADHD is complex, with rare and common variants involved. Common genetic variants (as indexed by a composite risk score) associated with clinical ADHD significantly predict ADHD and autistic-like behavioural traits in children from the general population, suggesting that ADHD lies at the extreme of normal trait variation. ADHD and other neurodevelopmental disorders share neurocognitive difficulties in several domains (e.g. impaired cognitive ability and executive functions). We hypothesised that ADHD composite genetic risk scores derived from clinical ADHD cases would also contribute to variation in neurocognitive abilities in the general population.MethodsChildren (N = 6,832) from a UK population cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC), underwent neurocognitive testing. Parent-reported measures of their children's ADHD and autistic-like traits were used to construct a behavioural latent variable of ‘neurodevelopmental traits’. Composite genetic risk scores for ADHD were calculated for ALSPAC children based on findings from an independent ADHD case–control genome-wide association study. Structural equation modelling was used to assess associations between ADHD composite genetic risk scores and IQ, working memory, inhibitory control and facial emotion recognition, as well as the latent ‘neurodevelopmental trait’ measure.ResultsThe results confirmed that neurocognitive and neurodevelopmental traits are correlated in children in the general population. Composite genetic risk scores for ADHD were independently associated with lower IQ (β = −.05, p < .001) and working memory performance (β = −.034, p = .013), even after accounting for the relationship with latent neurodevelopmental behavioural trait scores. No associations were found between composite genetic risk scores and inhibitory control or emotion recognition (p > .05).ConclusionsThese findings suggest that common genetic variants relevant to clinically diagnosed ADHD have pleiotropic effects on neurocognitive traits as well as behavioural dimensions in the general population. This further suggests that the well-recognised association between cognition and neurodevelopmental behavioural traits is underpinned at a biological level.

Brave new worlds--review and update on virtual reality assessment and treatment in psychosis.

In recent years, virtual reality (VR) research on psychotic disorders has been initiated. Several studies showed that VR can elicit paranoid thoughts about virtual characters (avatars), both in patients with psychotic disorders and healthy individuals. Real life symptoms and VR experiences were correlated, lending further support to its validity. Neurocognitive deficits and difficulties in social behavior were found in schizophrenia patients, not only in abstract tasks but also using naturalistic virtual environments that are more relevant to daily life, such as a city or encounters with avatars. VR treatments are conceivable for most dimensions of psychotic disorders. There is a small but expanding literature on interventions for delusions, hallucinations, neurocognition, social cognition, and social skills; preliminary results are promising. VR applications for assessment and treatment of psychotic disorders are in their infancy, but appear to have a great potential for increasing our understanding of psychosis and expanding the therapeutic toolbox.

Colour or shape: examination of neural processes underlying mental flexibility in posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a mental disorder that stems from exposure to one or more traumatic events. While PTSD is thought to result from a dysregulation of emotional neurocircuitry, neurocognitive difficulties are frequently reported. Mental flexibility is a core executive function that involves the ability to shift and adapt to new information. It is essential for appropriate social-cognitive behaviours. Magnetoencephalography (MEG), a neuroimaging modality with high spatial and temporal resolution, has been used to track the progression of brain activation during tasks of mental flexibility called set-shifting. We hypothesized that the sensitivity of MEG would be able to capture the abnormal neurocircuitry implicated in PTSD and this would negatively impact brain regions involved in set-shifting. Twenty-two soldiers with PTSD and 24 matched control soldiers completed a colour–shape set-shifting task. MEG data were recorded and source localized to identify significant brain regions involved in the task. Activation latencies were obtained by analysing the time course of activation in each region. The control group showed a sequence of activity that involved dorsolateral frontal cortex, insula and posterior parietal cortices. The soldiers with PTSD showed these activations but they were interrupted by activations in paralimbic regions. This is consistent with models of PTSD that suggest dysfunctional neurocircuitry is driven by hyper-reactive limbic areas that are not appropriately modulated by prefrontal cortical control regions. This is the first study identifying the timing and location of atypical neural responses in PTSD with set-shifting and supports the model that hyperactive limbic structures negatively impact cognitive function.

Functional neuroimaging of working memory in survivors of childhood brain tumors and healthy children: Associations with coping and psychosocial outcomes

Purpose: Pediatric brain tumors are the second most common cancer diagnosis in individuals under age 20 and research has documented significant neurocognitive, psychosocial, and emotional late effects. Associations among these deficits have not been adequately considered and the role of survivors’ coping with stress in relation to deficits is unknown. Further, research has yet to examine neurobiological processes related to neurocognitive, psychosocial, and emotional difficulties in survivors through the use of functional neuroimaging. Method: Questionnaire measures and functional neuroimaging were used to examine the neurocognitive, psychosocial, and emotional functioning and coping responses of survivors of pediatric brain tumors (N = 17; age 8–16) and healthy children (N = 15). Results: Survivors experienced elevated levels of psychosocial and behavioral/emotional difficulties relative to healthy controls and normative data. Increases in brain activation in prefrontal and other anterior regions in response to a working memory task were associated with better psychosocial functioning, use of engagement coping strategies, and less use of disengagement coping strategies. Regression analyses suggest coping accounts for a significant portion of the association between brain activation and behavioral/emotional functioning. Conclusions: This study extends late-effects research by examining neurobiological processes associated with psychosocial and emotional difficulties. These findings contribute to our understanding of difficulties in survivors and provide a foundation for research exploring these associations and mediators of deficits in future longitudinal studies.

The contribution of neurocognitive functioning to quality of life after childhood acute lymphoblastic leukemia

Neurocognitive late effects after childhood acute lymphoblastic leukemia (ALL) are well-documented, but their impact on quality of life (QOL) is not well understood. In this multi-site study, we examined the relative influence of neurocognitive functioning, steroid randomization (prednisone vs. dexamethasone), and demographic characteristics on QOL in first-remission survivors of childhood ALL. Participants included 263 ALL survivors (ages 7-17 years at the time of evaluation; mean age at diagnosis 3.9 years) who were treated on similar legacy Children's Cancer Group chemotherapy protocols and did not receive cranial radiation. Children completed detailed neuropsychological performance tests. The Pediatric QOL Inventory was completed by children and their parents. Participants were a mean of 9 years from diagnosis at the time of assessment (with a range of 4 to 13 years). Children and their parents reported lower mean child psychosocial QOL than healthy population norms (p < 0.05), but were not in the impaired range. Physical QOL was similar to population norms. Though neurocognitive difficulties were predominantly mild for the sample as a whole, neurocognitive deficits, specifically problems in verbal cognitive abilities and visual-motor integration skills, were significantly associated with poor physical (p < 0.01) and Psychosocial QOL (p < 0.01). QOL was not associated with previous steroid randomization. ALL survivors with neurocognitive deficits are at risk for poor QOL, with broad implications for their physical, social, and school functioning.

Évaluation de la cognition sociale en langue française chez l’adulte : outils disponibles et recommandations de bonne pratique clinique

Social cognition is described as the processes underlying interpersonal relationships. The crucial role of these processes in rehabilitation, especially in adult psychiatry, has raised needs of clinical assessment in this particular cognitive domain. However, social cognition is a multidimensional construct which has been studied in numerous recent international researches. This review is aimed at inventorying available tools in French language for social cognition assessment in adults, and at drawing recommendation for practice in clinical neuropsychology. Results show that despite the lack of available tools, the assessment of social cognition is feasible in several dimensions, such as facial emotion recognition, theory of mind, alexithymia and emotional awareness. Each of the identified tools has specific benefits and limits that delimitate their potential usefulness. Globally, the incomplete validation of tools, as well as their heterogeneity and their multidetermination should lead to some caution when assessing performances and interpreting results. However, when crossing assessments and controlling for basic neurocognitive difficulties, the identified tools can provide detailed information about each patient's social cognition profile. Studies remain necessary to further validate existing tools and to allow more reliable and diversified assessment.

Late neurocognitive effects in children and adolescents who have undercone oncological treatment: a rehabilitation model

Oncologists have been driven to face the need to reach their primary goal of patient recovery by reducing or preventing as much as possible late effects in cancer survivors of developmental age as a result of improved oncological treatments, increased survival rates, and their awareness that they are acting in a crucial phase of life. Late effects involve various systems of individual functioning: cardiovascular, respiratory, reproductive and neurocognitive. The aim of this study was to draw attention to late cognitive effects and underline the importance and usefulness of rehabilitation interventions in reducing not only learning difficulties, but also the problems related to socialisation and psychological unease. Neurocognitive outcomes are influenced by the type of cancer treatment, the time that has passed since its administration, surgery, tumour location, and the patient’s age and gender. Late effects are generally more severe in cases of radiotherapy, which seems to affect IQ, whereas chemotherapy only seems to affect neuropsychological abilities such as attention, concentration, memory, and executive and visuo-spatial functions. Cognitive outcomes therefore affect not only intellectual and educational functioning, but also social and psychological functioning. It is widely acknowledged that Butler and Copeland’s tripartite Cognitive Remediation Program (CRP) can benefit children and adolescents with neurocognitive difficulties due to oncological treatment. It not only improves attention and learning abilities, but also the ability to manage post-treatment cognitive dysfunction more effectively.

Neuroimaging and neurological findings in patients with hypochondroplasia and FGFR3 N540K mutation

Hypochondroplasia (HCH), an autosomal dominant skeletal dysplasia caused by mutations in the FGFR3 gene, has not been commonly associated with neurological problems. Temporal lobe dysgenesis associated with epilepsy was recently described in single patients. In this retrospective study, we assessed neurological and neuroimaging aspects of 13 FGFR3 (N540K) mutation verified HCH patients in Finland. Eight patients had neurocognitive difficulties, ranging from specific learning disorder (2/13) to mild intellectual disability (5/13) or global developmental delay (1/13). Six of 13 patients had a history of seizures or epilepsy. Eight patients had undergone MRI. They all had structural abnormalities consistent with temporal lobe dysgenesis. Six patients had peritrigonal white matter reduction, and 4 had abnormally shaped lateral ventricles. We recommend a close follow-up of development in patients with HCH and a low threshold for neuroimaging.

The role of verbal and nonverbal memory in the Family Pictures Subtest: Data from children with specific language impairment

This study examined the contribution of verbal and visual memory to performance on the Family Pictures subtest of the Children’s Memory Scale. This subtest purports to assess declarative memory functioning in the visual/nonverbal domain. A total of 115 nine-year-old children participated in this study. Fifty-eight had specific language impairment (SLI), whilst the remaining 57 were typically developing (TD), with no history of language difficulties. Results showed that the children with SLI, who had intact declarative memory for visual but not verbal information, obtained significantly lower scores on the Family Pictures subtest when compared to the TD group. Regression analyses revealed that across the entire sample, individual differences on the Family Pictures subtest was best predicted by a measure of verbal working memory. These results question whether the Family Pictures subtest can be considered a measure of visual memory in pediatric populations. These results have implications for the interpretation of scores on this subtest regarding the nature of the types of neurocognitive difficulties children may exhibit.

Cardiorespiratory Fitness in Survivors of Pediatric Posterior Fossa Tumor

Advances in medical therapies have greatly improved survivorship rates in children diagnosed with brain tumor; as a result, morbidities associated with survivorship have become increasingly important to identify and address. In general, pediatric posterior fossa tumor survivors tend to be less physically active than peers. This may be related to late effects of diagnosis and treatment, including cardiovascular, endocrine, psychological, and neurocognitive difficulties. Exercise has been shown to be effective in improving physical functioning, mood, and even cognitive functioning. Consequently, the benefits of physical exercise need to be explored and incorporated into the daily lives of pediatric posterior fossa tumor survivors. The primary aim of the present study was to establish the feasibility and safety of cardiorespiratory fitness testing in pediatric posterior fossa tumor survivors who had received cranial radiation therapy. In addition, comparing our cohort with previously published data, we found that pediatric posterior fossa tumor survivors tended to be less fit than children with pulmonary disease and healthy controls and approximately as fit as children with chronic heart disease and survivors of other types of childhood cancer. The importance of cardiorespiratory fitness in pediatric posterior fossa tumor survivors is discussed along with implications for future directions.

The psychosocial challenges of solid organ transplant recipients during childhood

A large proportion of pediatric solid organ transplant recipients are young children, yet dedicated studies on the challenges faced by these patients are sparse. The present article aims to provide a summary of key considerations for pediatric solid organ transplant teams, describing what challenges are more likely for younger patients and how they might identify and address these circumstances. Our findings suggest that the mental health of patients and caregivers, issues at school, neurocognitive difficulties, and self-management are areas of particular relevance for children. We offer several recommendations that stem from these identified areas of concern. Dedicated focus on the well-being of younger patients could in the long-term stave off adverse events that are often associated with adolescence. In the short-term, certainly intervening in any of these domains could lead to improved quality of life during childhood.

Post-treatment Lyme disease syndrome symptomatology and the impact on life functioning: is there something here?

PurposeA subset of patients treated for Lyme disease report persistent or recurrent symptoms of unknown etiology named post-treatment Lyme disease syndrome (PTLDS). This study aims to describe a cohort of participants with early, untreated Lyme disease, and characterize post-treatment symptomatology and functional impact of PTLDS over time.MethodsSixty-three participants with erythema migrans and systemic symptoms were enrolled in a prospective cohort study. Participants underwent physical exams and clinical assessments, and completed the SF-36 (daily life functioning) and the Beck Depression Inventory, Second Edition (BDI-II) (depression), at each of five visits over a period of 6 months.ResultsSigns of Lyme disease disappeared post-treatment; however, new-onset patient-reported symptoms increased or plateaued over time. At 6 months, 36% of patients reported new-onset fatigue, 20% widespread pain, and 45% neurocognitive difficulties. However, less than 10% reported greater than “minimal” depression across the entire period. Those with PTLDS (36%) did not differ significantly from those without with respect to demographics, pre-treatment SF-36, and BDI-II scores. Statistically significant differences were found over time on the Role Physical, Vitality, Social Functioning, Role Emotional, and Mental Health subscales (with a trend toward significance for the remaining three subscales of Physical Functioning, Bodily Pain, and General Health) of the SF-36 between those with an eventual PTLDS diagnosis and those without when measured at 6 months.ConclusionsUnlike clinical signs of Lyme disease, new-onset symptoms are reported by a subset of participants without evidence of depressive symptomatology. Patients who developed PTLDS had significantly lower life functioning compared to those without PTLDS. We propose future avenues for researching infection-triggered symptoms resulting from multiple mechanisms.

Genetic associations of fatigue and other symptom domains of the acute sickness response to infection

The acute sickness response to infection is a conserved set of changes in physiology and behaviour, featuring fever, fatigue, musculo-skeletal pain, disturbed mood, and cognitive difficulties. The manifestations differ somewhat between individuals, including those infected with pathogens which do not have genetic variability--suggesting host determinants. Principal components analysis (PCA) was applied to acute phase, self-report symptom data from subjects in the Dubbo Infection Outcomes Study (n=296) to empirically derive indices of fatigue, pain, neurocognitive difficulties, and mood disturbance, as well as overall illness severity. Associations were sought with functional single nucleotide polymorphisms (SNPs) in the cytokine genes, interleukin (IL)-6, tumour necrosis factor (TNF)-α, interferon (IFN)-γ, and IL-10. The summed individual symptom indices correlated with overall severity and also with functional status. The relative contribution of individual symptom domains to the overall illness was stable over time within subjects, but varied between subjects with the same infection. The T allele of the IFN-γ +874 T/A SNP was associated with increased fatigue (p=0.0003; OR: 3.3). The C allele of the IL-10 -592 C/A SNP exerted a protective effect on neurocognitive difficulties (p=0.017; OR: 0.52); while the A allele for the IL-10 -592 SNP was associated with increased mood disturbance (p=0.044; OR: 1.83), as was the G allele of the IL-6 -174 G/C SNP (p=0.051; OR: 1.83). The acute sickness response has discrete symptom domains including fatigue, which have unique genetic associations. These data provide novel insights into the pathophysiology of fatigue states.

Evidence of impaired neurocognitive functioning in school‐age children awaiting cardiac surgery

Children with congenital heart disease (CHD) are at risk of developing neurocognitive problems. However, as these problems are usually identified after cardiac surgery, it is unclear whether they resulted from the surgery or whether they pre-existed and hence might be explained by complications and events associated with the heart disease itself. The purpose of this study was to examine whether neurocognitive deficits commonly reported after cardiac surgery are present before surgery. Forty-five children (22 males, 23 females; mean age 11 y 6 mo, SD 3 y 0 mo) with cyanotic and acyanotic heart diseases scheduled for elective cardiac surgery were compared with 41 healthy peers (17 males, 24 females; mean age 11 y 10 mo, SD 2 y 10 mo) for attention and processing speed, construction, motor speed, motor planning and fluency, and visual memory. Twenty-three children in the patient group were awaiting their first cardiac surgery and 22 were awaiting follow-up surgery. The patients showed manifest neurocognitive difficulties. Their performance was inferior to that of the healthy comparison group for motor planning (p=0.02) and visual memory (p=0.01). The same neurocognitive profile was found in the group of patients awaiting their first cardiac operation. School-age children with various forms of CHD are at risk of neurocognitive impairments before cardiac surgery.

Neuropsychological decline/improvement in opsoclonus myoclonus ataxia

Opsoclonus myoclonus ataxia (OMA) is a rare neurological disorder (incidence = ∼1/5 million) primarily associated with involuntary conjugate saccadic eye movements, involuntary muscle jerks, cerebellar ataxia, and neuropsychological impairments. Unfortunately, there is limited published data regarding the nature and course of neuropsychological impairments following OMA diagnosis and treatment. This study presents neuropsychological data obtained at 1, 4, and 18 months post-diagnosis of a 52-year-old male with OMA. The patient initially demonstrated significant global neurocognitive, psychomotor, and psychological difficulties with substantial improvement over time. Treatment included medication management, physical rehabilitation, and psychological intervention.