Dissociation of Reliability, Heritability, and Predictivity in Coarse- and Fine-Scale Functional Connectomes during Development.

The functional connectome supports information transmission through the brain at various spatial scales, from exchange between broad cortical regions to finer-scale, vertex-wise connections that underlie specific information processing mechanisms. In adults, while both the coarse- and fine-scale functional connectomes predict cognition, the fine scale can predict up to twice the variance as the coarse-scale functional connectome. Yet, past brain-wide association studies, particularly using large developmental samples, focus on the coarse connectome to understand the neural underpinnings of individual differences in cognition. Using a large cohort of children (age 9-10 years; n = 1,115 individuals; both sexes; 50% female, including 170 monozygotic and 219 dizygotic twin pairs and 337 unrelated individuals), we examine the reliability, heritability, and behavioral relevance of resting-state functional connectivity computed at different spatial scales. We use connectivity hyperalignment to improve access to reliable fine-scale (vertex-wise) connectivity information and compare the fine-scale connectome with the traditional parcel-wise (coarse scale) functional connectomes. Though individual differences in the fine-scale connectome are more reliable than those in the coarse-scale, they are less heritable. Further, the alignment and scale of connectomes influence their ability to predict behavior, whereby some cognitive traits are equally well predicted by both connectome scales, but other, less heritable cognitive traits are better predicted by the fine-scale connectome. Together, our findings suggest there are dissociable individual differences in information processing represented at different scales of the functional connectome which, in turn, have distinct implications for heritability and cognition.

Leveraging the adolescent brain cognitive development study to improve behavioral prediction from neuroimaging in smaller replication samples.

Neuroimaging is a popular method to map brain structural and functional patterns to complex human traits. Recently published observations cast doubt upon these prospects, particularly for prediction of cognitive traits from structural and resting state functional magnetic resonance imaging (MRI). We leverage baseline data from thousands of children in the Adolescent Brain Cognitive DevelopmentSM Study to inform the replication sample size required with univariate and multivariate methods across different imaging modalities to detect reproducible brain-behavior associations. We demonstrate that by applying multivariate methods to high-dimensional brain imaging data, we can capture lower dimensional patterns of structural and functional brain architecture that correlate robustly with cognitive phenotypes and are reproducible with only 41 individuals in the replication sample for working memory-related functional MRI, and ~ 100 subjects for structural and resting state MRI. Even with 100 random re-samplings of 100 subjects in discovery, prediction can be adequately powered with 66 subjects in replication for multivariate prediction of cognition with working memory task functional MRI. These results point to an important role for neuroimaging in translational neurodevelopmental research and showcase how findings in large samples can inform reproducible brain-behavior associations in small sample sizes that are at the heart of many research programs and grants.

CD4 nadir and neurocognitive trajectories in people living with HIV.

Human immunodeficiency virus-associated neurocognitive disorders persist in the combination antiretroviral therapy era. CD4 nadir is a well-established predictor of cognition cross-sectionally, but its impact on longitudinal neurocognitive (NC) trajectories is unclear. The few studies on this topic examined trajectories of global cognition, rather than specific NC domains. The current study examined CD4 nadir in relation to domain-specific NC decline. 132 HIV + adults from the Temple/Drexel Comprehensive NeuroHIV Center, Clinical and Translational Research Support Core Cohort were administered comprehensive NC assessments longitudinally, with last visit occurring an average of 12 years after CD4 nadir. Linear mixed models were used to examine CD4 nadir in relation to longitudinal NC trajectories in three empirically identified NC domains: speed/executive function (S/EF), visuospatial memory (VM), and verbal fluency (VF). CD4 nadir was associated with change in VF (p = 0.020), but not with S/EF or VM. Specifically, those with CD4 nadir < 200 demonstrated increasing VF over time (p = .002), whereas those with CD4 nadir > 200 demonstrated stable VF (p = .568), though these differing trajectories may partly reflect regression to the mean or differential practice effect. CD4 dynamics over time were analyzed as potential mechanisms for the identified associations, with mixed findings. While low CD4 nadir has been associated with weaker neurocognition among people living with HIV, the results of this study suggest that low CD4 nadir is not associated with ongoing decline a decade later. Nadir-related deficits in VF may be stable or even improve over time, possibly reflecting the beneficial cognitive effects of long-term treatment and immune reconstitution.

It's about time: mitigating cancer-related cognitive impairments through findings from computational models of the Wisconsin Card Sorting Task.

BACKGROUND: Many cancer survivors experience cancer-related cognitive impairment (CRCI), often with significant negative consequences across various life domains. Emerging evidence suggests that allowing additional time to process information before acting may be a useful strategy for those with CRCI to mitigate some of its impacts. The Wisconsin Card Sorting Task (WCST), a measure of general cognition, has shown that for some cancer survivors, longer task completion time facilitates similar task performance outcomes to control populations concerning perseveration errors; a key performance metric of the WCST. However, assessing if this strategy may be useful, as well as determining for whom it may be useful, with regard to strengths and weaknesses among select cognitive domains, is challenging due to factors such as the problem of task impurity. Accordingly, this study provides an initial computational and experimental assessment of whether additional time to process information before acting is a useful strategy for those with CRCI. METHODS: We simulated individual cognitive differences observed in humans by varying contributions of executive functioning components (updating, shifting, inhibition) to yield 48 distinct computational models of the WCST. Our main manipulation was then to provide these models with more or less time (at three levels of 20, 40 and 60 cycles) before models executed an action to sort a given card. We compared the number of perseveration errors on the WCST produced by the computational models. Additionally, we determined models that simulated the performance of cancer survivors on the WCST by comparing the number of perseveration errors produced by the models to human data. RESULTS: Additional processing time resulted in the models producing significantly fewer perseveration errors, supporting our hypothesis. In addition, 8 unique models simulated the performance of cancer survivors on the WCST. Additional time appeared to have a positive influence on performance primarily by mitigating the impacts of severe inhibition impairments. For more severe global executive function impairments, a substantial amount of additional time was required to mitigate the impacts of the impairments. For the most severe impairments, additional time was unable to adequately mitigate the impact on performance. CONCLUSION: Additional processing time may be a useful strategy to rectify perseveration errors among cancer survivors with CRCI. Our findings have implications for the development of practical strategies, such as workload and deadline management in occupational settings, which may mitigate the negative effects of CRCI.

Domain-specific associations between psychopathology and neurocognitive functioning.

BACKGROUND: Neurocognitive dysfunction is a transdiagnostic finding in psychopathology, but relationships among cognitive domains and general and specific psychopathology dimensions remain unclear. This study aimed to examine associations between cognition and psychopathology dimensions in a large youth cohort. METHOD: The sample (N = 9350; age 8-21 years) was drawn from the Philadelphia Neurodevelopmental Cohort. Data from structured clinical interviews were modeled using bifactor confirmatory factor analysis (CFA), resulting in an overall psychopathology ('p') factor score and six orthogonal psychopathology dimensions: dysphoria/distress, obsessive-compulsive, behavioral/externalizing, attention-deficit/hyperactivity, phobias, and psychosis. Neurocognitive data were aggregated using correlated-traits CFA into five factors: executive functioning, memory, complex cognition, social cognition, and sensorimotor speed. We examined relationships among specific and general psychopathology dimensions and neurocognitive factors. RESULTS: The final model showed both overall and specific associations between cognitive functioning and psychopathology, with acceptable fit (CFI = 0.91; TLI = 0.90; RMSEA = 0.024; SRMR = 0.054). Overall psychopathology and most psychopathology dimensions were negatively associated with neurocognitive functioning (phobias [p < 0.0005], behavioral/externalizing [p < 0.0005], attention-deficit/hyperactivity [p < 0.0005], psychosis [p < 0.0005 to p < 0.05]), except for dysphoria/distress and obsessive-compulsive symptoms, which were positively associated with complex cognition (p < 0.05 and p < 0.01, respectively). CONCLUSION: By modeling a broad range of cognitive and psychopathology domains in a large, diverse sample of youth, we found aspects of neurocognitive functioning shared across clinical phenotypes, as well as domain-specific patterns. Findings support transdiagnostic examination of cognitive performance to parse variability in the link between neurocognitive functioning and clinical phenotypes.

Longitudinal study of traumatic-stress related cellular and cognitive aging.

Traumatic stress is associated with both accelerated epigenetic age and increased risk for dementia. Accelerated epigenetic age might link symptoms of traumatic stress to dementia-associated biomarkers, such as amyloid-beta (Aß) proteins, neurofilament light (NFL), and inflammatory molecules. We tested this hypothesis using longitudinal data obtained from 214 trauma-exposed military veterans (85 % male, mean age at baseline: 53 years, 75 % White) who were assessed twice over the course of an average of 5.6 years. Cross-lagged panel mediation models evaluated measures of lifetime posttraumatic stress disorder and internalizing and externalizing comorbidity (assessed at Time 1; T1) in association with T1 epigenetic age (per the GrimAge algorithm) and T1 plasma markers of neuropathology along with bidirectional temporal paths between T1 and T2 epigenetic age and the plasma markers. Results revealed that a measure of externalizing comorbidity was associated with accelerated epigenetic age (ß = 0.30, p <.01), which in turn, was associated with subsequent increases in Aß-40 (ß = 0.20, p <.001), Aß-42 (ß = 0.18, p <.001), and interleukin-6 (ß = 0.18, p <.01). T1 advanced epigenetic age and the T1 neuropathology biomarkers NFL and glial fibrillary acidic protein predicted worse performance on T2 neurocognitive tasks assessing working memory, executive/attentional control, and/or verbal memory (ps = 0.03 to 0.009). Results suggest that advanced GrimAge is predictive of subsequent increases in neuropathology and inflammatory biomarkers as well as worse cognitive function, highlighting the clinical significance of this biomarker with respect to cognitive aging and brain health over time. The finding that advanced GrimAge mediated the association between psychiatric comorbidity and future neuropathology is important for understanding potential pathways to neurodegeneration and early identification of those at greatest risk.

Influence of maternal folate depletion on Art3 DNA methylation in the murine adult brain; potential consequences for brain and neurocognitive health.

The developmental origins of health and disease hypothesis suggest early-life environment impacts health outcomes throughout the life course. In particular, epigenetic marks, including DNA methylation, are thought to be key mechanisms through which environmental exposures programme later-life health. Adequate maternal folate status before and during pregnancy is essential in the protection against neural tube defects, but data are emerging that suggest early-life folate exposures may also influence neurocognitive outcomes in childhood and, potentially, thereafter. Since folate is key to the supply of methyl donors for DNA methylation, we hypothesize that DNA methylation may be a mediating mechanism through which maternal folate influences neurocognitive outcomes. Using bisulphite sequencing, we measured DNA methylation of five genes (Art3, Rsp16, Tspo, Wnt16, and Pcdhb6) in the brain tissue of adult offspring of dams who were depleted of folate (n = 5, 0.4 mg folic acid/kg diet) during pregnancy (~19-21 days) and lactation (mean 22 days) compared with controls (n = 6, 2 mg folic acid/kg diet). Genes were selected as methylation of their promoters had previously been found to be altered by maternal folate intake in mice and humans across the life course, and because they have potential associations with neurocognitive outcomes. Maternal folate depletion was significantly associated with Art3 gene hypomethylation in subcortical brain tissue of adult mice at 28 weeks of age (mean decrease 6.2%, P = .03). For the other genes, no statistically significant differences were found between folate depleted and control groups. Given its association with neurocognitive outcomes, we suggest Art3 warrants further study in the context of lifecourse brain health. We have uncovered a potential biomarker that, once validated in accessible biospecimens and human context, may be useful to track the impact of early-life folate exposure on later-life neurocognitive health, and potentially be used to develop and monitor the effects of interventions.

Relationship between subjective cognitive functioning and fluid and crystallized cognitive abilities in bipolar disorder.

OBJECTIVE: People with bipolar disorder (BD) often show inaccurate subjective ratings of their objective cognitive function. However, it is unclear what information individuals use to formulate their subjective ratings. This study evaluated whether people with BD are likely using information about their crystallized cognitive abilities (which involve an accumulated store of verbal knowledge and skills and are typically preserved in BD) or their fluid cognitive abilities (which involve the capacity for new learning and information processing in novel situations and are typically impaired in BD) to formulate their subjective cognitive ratings. METHOD: Eighty participants diagnosed with BD and 55 control volunteers were administered cognitive tests assessing crystallized and fluid cognitive abilities. Subjective cognitive functioning was assessed with the Cognitive Failures Questionnaire (CFQ), daily functioning was rated using the Multidimensional Scale of Independent Functioning (MSIF) and the Global Assessment of Functioning Scale (GAF), and quality of life was assessed with the Quality of Life in Bipolar Disorder scale (QoL.BD). RESULTS: The BD group exhibited considerably elevated subjective cognitive complaints relative to controls. Among participants with BD, CFQ scores were associated with fluid cognitive abilities including measures of memory and executive function, but not to crystallized abilities. After controlling for objective cognition and depression, higher cognitive complaints predicted poorer psychosocial outcomes. CONCLUSIONS: Cognitive self-reports in BD may represent a metacognitive difficulty whereby cognitive self-appraisals are distorted by a person's focus on their cognitive weaknesses rather than strengths. Moreover, negative cognitive self-assessments are associated with poorer daily functioning and diminished quality of life.

Higher order neurocognition in pediatric brain tumor survivors: What can we learn from white matter microstructure?

BACKGROUND: Pediatric brain tumor survivors (PBTS) experience neurocognitive late effects, including problems with working memory, processing speed, and other higher order skills. These skill domains are subserved by various white matter (WM) pathways, but not much is known about these brain-behavior links in PBTS. This study examined the anterior corona radiata (ACR), inferior fronto-occipital fasciculi (IFOF), and superior longitudinal fasciculi (SLF) by analyzing associations among diffusion metrics and neurocognition. PROCEDURE: Thirteen PBTS and 10 healthy controls (HC), aged 9-14 years, completed performance-based measures of processing speed and executive function, and parents rated their child's day-to-day executive skills. Children underwent magnetic resonance imaging (MRI) with diffusion weighted imaging that yielded fractional anisotropy (FA) and mean diffusivity (MD) values. Independent samples t-tests assessed group differences on neurocognitive and imaging measures, and pooled within-group correlations examined relationships among measures across groups. RESULTS: PBTS performed more poorly than HC on measures of processing speed, divided attention, and shifting (d = -1.08 to -1.44). WM microstructure differences were significant in MD values for the bilateral SLF and ACR, with PBTS showing higher diffusivity (d = 0.75 to 1.21). Better processing speed, divided attention, and shifting were associated with lower diffusivity in the IFOF, SLF, and ACR, but were not strongly correlated with FA. CONCLUSIONS: PBTS demonstrate poorer neurocognitive functioning that is linked to differences in WM microstructure, as evidenced by higher diffusivity in the ACR, SLF, and IFOF. These findings support the use of MD in understanding alterations in WM microstructure in PTBS and shed light on potential functions of these pathways.

Episodes of acute methotrexate-related neurotoxicity linked to compromised long-term neurocognitive function.

Methotrexate is a critical component of curative chemotherapy for pediatric acute lymphoblastic leukemia (ALL), but is associated with neurotoxicity. Information on long-term outcomes following an acute neurotoxic event is limited. Therefore, this report compares neurocognitive performance more than 12 months post diagnosis (mean = 4 years) between ALL patients with (n = 25) and without (n = 146) a history of acute neurotoxicity. Compared to children with no documented on-treatment neurotoxic event, children who experienced a neurotoxic event during treatment exhibited poorer performance on measures of fine motor function (p = .02) and attention (p = .02). Children with ALL who experience acute neurotoxicity may be candidates for early neuropsychological screening and intervention.

Association of empathy with clinical symptoms and cognitive function in chronic schizophrenia patients with and without suicide attempts.

Cognitive impairment is recognized as a risk factor for suicide in schizophrenia (SZ) patients. Despite empathy being an important aspect of social cognition, the association between suicidal behavior and empathy has received little attention. We aimed to compare empathy and neurocognition in SZ patients with and without suicide attempts (SAs), and to explore the relationship between empathy, neurocognition, and clinical symptoms in SZ patients with and without SAs. Data on SAs and socio-demographic characteristics were collected from 628 chronic SZ patients. The patients' symptomatology was measured by the Positive and Negative Syndrome Scale (PANSS). Empathy and neurocognition were assessed with the Interpersonal Reactivity Index (IRI) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), respectively. Patients with SAs performed better on all IRI domains (except for Perspective Taking) and total scores. Regression results showed that negative symptoms, positive symptoms, and duration of illness were independently associated with IRI total score in patients without SAs (adjusted R2 = 0.048). In patients without SAs, negative symptoms, general psychopathology, education, age, and sex were independently associated with RBANS total score (adjusted R2 = 0.265), while in patients with SAs, education, PANSS total score, and age at onset were independently associated with RBANS total score (adjusted R2 = 0.456). Our results show that SZ patients with SAs may have better empathic performance than patients without SAs. In chronic SZ patients, negative and positive symptoms may have different effects on cognition in the SAs and non-SAs groups.

Altered patterns of dynamic functional connectivity of brain networks in deficit and non-deficit schizophrenia.

This study aims to investigate the altered patterns of dynamic functional network connectivity (dFNC) between deficit schizophrenia (DS) and non-deficit schizophrenia (NDS), and further explore the associations with cognitive impairments. 70 DS, 91 NDS, and 120 matched healthy controls (HCs) were enrolled. The independent component analysis was used to segment the whole brain. The fMRI brain atlas was used to identify functional networks, and the dynamic functional connectivity (FC) of each network was detected. Correlation analysis was used to explore the associations between altered dFNC and cognitive functions. Four dynamic states were identified. Compared to NDS, DS showed increased FC between sensorimotor network and default mode network in state 1 and decreased FC within auditory network in state 4. Additionally, DS had a longer mean dwell time of state 2 and a shorter one in state 3 compared to NDS. Correlation analysis showed that fraction time and mean dwell time of states were correlated with cognitive impairments in DS. This study demonstrates the distinctive altered patterns of dFNC between DS and NDS patients. The associations with impaired cognition provide specific neuroimaging evidence for the pathogenesis of DS.

Mentalizing impairments and hypermentalizing bias in individuals with first-episode schizophrenia-spectrum disorder and at-risk mental state: the differential roles of neurocognition and social anxiety.

Mentalizing, or theory of mind (ToM), impairments and self-referential hypermentalizing bias are well-evident in schizophrenia. However, findings compared to individuals with at-risk mental states (ARMS) are inconsistent, and investigations into the relationship between social cognitive impairments and social anxiety in the two populations are scarce. This study aimed to examine and compare these deficits in first-episode schizophrenia-spectrum disorder (FES) and ARMS, and to explore potential specific associations with neurocognition and symptomatology. Forty patients with FES, 40 individuals with ARMS, and 40 healthy controls (HC) completed clinical assessments, a battery of neurocognitive tasks, and three social cognitive tasks. The comic strip and hinting tasks were used to measure non-verbal and verbal mentalizing abilities, and the gaze perception task was employed to assess self-referential hypermentalizing bias. FES and ARMS showed comparable mentalizing impairments and self-referential hypermentalizing bias compared to HC. However, only ambiguous self-referential gaze perception (SRGP) bias remained significantly different between three groups after controlling for covariates. Findings suggested that self-referential hypermentalizing bias could be a specific deficit and may be considered a potential behavioral indicator in early-stage and prodromal psychosis. Moreover, working memory and social anxiety were related to the social cognitive impairments in ARMS, whereas higher-order executive functions and positive symptoms were associated with the impairments in FES. The current study indicates the presence of stage-specific mechanisms of mentalizing impairments and self-referential hypermentalizing bias, providing insights into the importance of personalized interventions to improve specific neurocognitive domains, social cognition, and clinical outcomes for FES and ARMS.

Empirically derived profiles of neurocognitive functioning in youth and young adults with sickle cell disease.

OBJECTIVE: Sickle cell disease (SCD) is an inherited blood disorder associated with neurocognitive deficits. In contrast to variable-centered approaches, no known research has utilized person-centered strategies to identify multidimensional patterns of neurocognitive functioning of an individual with SCD. The purpose of the present study was to create empirically derived profiles and identify predictors of neurocognitive functioning subgroups among youth and young adults with SCD. METHODS: Individuals with SCD (N = 393, mean age 14.05 years, age range 8-24, 50.4% female/49.6% male) completed neurocognitive assessments. Latent profile analysis derived subgroups/classes of neurocognitive functioning and determined relations with demographic and medical variables. RESULTS: Three latent classes emerged: average functioning (n = 102, 27%), low average functioning (n = 225, 60%), and exceptionally low functioning (n = 46, 12%). Older age was associated with membership in the low average and exceptionally low functioning groups (relative to the average group). Being prescribed hydroxyurea was associated with membership in the average functioning group (relative to the low average group) and absence of hydroxyurea use was associated with membership in the exceptionally low group (relative to the low average group). Lower social vulnerability was associated with membership in the average functioning group compared to the low average and exceptionally low groups. CONCLUSIONS: Clinicians can help reduce disparities in cognitive development for individuals with SCD by promoting early treatment with hydroxyurea and implementing methods to reduce social vulnerabilities that can interfere with access to evidence-based care.

Testing the role of associative learning in evidence-based treatments for anorexia nervosa.

Treatments for anorexia nervosa (AN) remain ineffective for many patients. Processes that can account for differential treatment outcomes remain mostly unknown. We propose that the field test the role of associative learning in current psychological treatments. We hold that this line of research could yield actionable information for understanding non-response and improving long-term outcomes. To make this argument, we define associative learning and outline its proposed role in understanding psychiatric disorders and their treatment. We then briefly review data exploring associative learning in AN. We argue that associative learning processes are implicitly implicated in existing treatments; by this rationale, baseline differences in learning may interfere with treatment response. Finally, we outline future research to test our hypotheses. Altogether, future research aimed at better understanding how associative learning may contribute to AN symptom persistence has the potential to inform novel directions in intervention research. PUBLIC SIGNIFICANCE: There is a pressing need to improve outcomes in treatments for anorexia nervosa (AN). We propose that individual differences in associative learning-the ability to form and update associations between cues, contexts, behaviors, and outcomes-may account for differential response to existing treatments. Undertaking this research could provide an understanding of how current treatments work and inform new approaches for those who may be at risk of poor outcomes.

Relationship between cognitive function and functional outcomes in remitted major depression.

BACKGROUND: Few studies have focused on functional impairment in depressed patients during symptomatic remission. The exact relationship between cognitive performance and functional outcomes of patients with Major depressive disorder (MDD) remains unclear. METHODS: Participants diagnosed with MDD were included and interviewed at both baseline and follow-up. Cognitive function was assessed during acute episodes using the Cambridge Neuropsychological Test Automated Battery (CANTAB), which targeted attention (Rapid Visual Processing - RVP), visual memory (Pattern Recognition Memory - PRM), and executive function (Intra-Extra Dimensional Set Shift - IED). The 17-item Hamilton Depression Scale (HAMD) was used for symptom assessment. Participants were divided into two groups based on their SDSS (Social Disability Screening Schedule) scores, and the differences between their demographic information, HAMD scores, and baseline CANTAB test results were compared. Logistic regression analysis was used to identify cognitive predictors of social function during symptomatic remission. RESULTS: According to the SDSS score at follow-up, 103 patients were divided into the normal social function group (n = 81,78.6%) and the poor social function group (n = 22, 21.4%) during clinical remission. Participants with poorer social function performed worse in the visual memory (PRM) and executive function tests (IED) at the baseline. Logistic regression analysis suggested that performance on the PRM (95%CI = 0.31-0.93, p = 0.030) and IED (95%CI = 1.01-1.13, p = 0.014) tests, instead of less severe symptoms, significantly contributed to functional outcomes. CONCLUSION: Better performance in visual memory and executive function during acute episodes may predict better social functional outcomes in individuals with MDD. A potential early intervention to improve social function in individuals with MDD could include the treatments for executive function and visual memory.

Reexamination of the relationships among neurocognition, self-defeatist beliefs, experiential negative symptoms, and social functioning in a sample of patients diagnosed with chronic schizophrenia and schizoaffective disorder.

PURPOSE: This study proposed and evaluated a theoretical model for exploring the relationships between neurocognition, self-defeatist beliefs, experiential negative symptoms, and social functioning in individuals with chronic schizophrenia. METHOD: The study recruited 229 individuals given a diagnosis of schizophrenia and schizoaffective disorders from outpatient clinics and the day ward of a mental health hospital. After informed consent was obtained, the participants underwent assessments using the backward digit span, the digit symbol, and measures of self-defeatist beliefs, experiential negative symptoms, and social functioning. A structural equation model was applied to assess the fitness of the hypothesized model, with indices such as the goodness-of-fit index, comparative fit index, root mean square error of approximation, and standardized root mean square residual being used for model evaluation. RESULTS: The hypothesized model had an adequate fit. The study findings indicated that neurocognition might indirectly influence self-defeatist beliefs through its effect on experiential negative symptoms. Contrary to expectations, the study did not observe a direct influence of neurocognition, self-defeatist beliefs, or negative symptoms on social functioning. The revised model revealed the role of experiential negative symptoms in mediating the association between neurocognition and social functioning. However, self-defeatist beliefs did not significantly affect social functioning. DISCUSSION: Before modifying negative thoughts, enhancement of self-awareness ability can help improve negative symptoms and thereby improve the performance of social functions. Future research should develop a hierarchical program of negative symptoms, from cognition rehabilitation to enhancement of self-awareness, and end with modifying maladaptive beliefs.

Integrative Neuro-social cognitive Strategy Programme for Instilling REcovery (INSPIRE): a community-based cognitive remediation trial-study procotol.

BACKGROUND: Adults with schizophrenia experience a range of neurocognitive problems that affect their daily functioning. Evidence for the efficacy of cognitive remediation in schizophrenia has been established, but its implementation in under-resourced community-based settings is less well-studied. In recent years, interventions have also focused on the strategy-learning approach in favor of drill-and-practice. Moreover, there is an increasing recognition to address social cognition and negative symptoms alongside neurocognition. This study attempts to carry out cognitive remediation in a community mental health setting. The Neuropsychological and Educational Approach to Remediation (NEAR) is used as the cognitive remediation intervention. Neurocognitive and social cognitive games will be introduced during the computer-assisted cognitive exercises sessions. In addition, the instructional technique will foster the use of metacognition and cognitive strategies. Moreover, metamotivation training will be the focus of some bridging sessions to enhance motivation to engage in goal-directed learning behaviors. The aims of the study are to 1) investigate the effects of cognitive remediation on neurocognition, social cognition and functional outcomes of participants with schizophrenia/schizoaffective disorders in community mental health settings; and 2) explore the mediators for change (eg: metamotivation, metacognition and negative symptoms) in cognitive performance and functional outcomes. METHODS: This randomized controlled trial will be conducted in three Singapore Anglican Community Services (SACS) centers, where standard psychiatric rehabilitation is delivered. Participants who are randomized to the experimental arm will receive cognitive remediation and psychiatric rehabilitation, while those randomized to the control arm will receive standard psychiatric rehabilitation only. Cognitive remediation is carried out three times a week for 12 weeks. It consists of computer-assisted cognitive exercises, as well as bridging groups to aid transfer of learning to daily living. Baseline, post-intervention and eight-week follow-up measurements will be collected. Group by time differences in cognitive performance, negative symptoms, metamotivation, metacognition, functioning and recovery will be analyzed across the three time points. Mediators for improvement in cognitive performance and functioning will also be explored. DISCUSSION: Findings of this research will add to the body of knowledge about the key therapeutic ingredients within a strategy-based cognitive remediation program and improve its implementation within under-resourced community settings. TRIAL REGISTRATION: This study has been registered with ClinicalTrials.gov (ID: NCT06286202). Date of registration: 29 February 2024. Date of last update: 21 May 2024.

Predicting long-term neurocognitive outcome after pediatric intensive care unit admission for bronchiolitis-preliminary exploration of the potential of machine learning.

PURPOSE: For successful prevention and intervention, it is important to unravel the complex constellation of factors that affect neurocognitive functioning after pediatric intensive care unit (PICU) admission. This study aims (1) to elucidate the potential relevance of patient and PICU-related characteristics for long-term adverse neurocognitive outcome after PICU admission for bronchiolitis, and (2) to perform a preliminary exploration of the potential of machine learning as compared to linear regression to improve neurocognitive outcome prediction in a relatively small sample of children after PICU admission. METHODS: This cross-sectional observational study investigated 65 children aged 6-12 years with previous PICU admission for bronchiolitis (age ≤ 1 year). They were compared to demographically comparable healthy peers (n = 76) on neurocognitive functioning. Patient and PICU-related characteristics used for the prediction models were as follows: demographic characteristics, perinatal and disease parameters, laboratory results, and intervention characteristics, including hourly validated mechanical ventilation parameters. Neurocognitive outcome was measured by intelligence and computerized neurocognitive testing. Prediction models were developed for each of the neurocognitive outcomes using Regression Trees, k-Nearest Neighbors, and conventional linear regression analysis. RESULTS: The patient group had lower intelligence than the control group (p < .001, d = -0.59) and poorer performance in neurocognitive functions, i.e., speed and attention (p = .03, d = -0.41) and verbal memory (p < .001, d = -0.60). Lower intelligence was predicted by lower birth weight and lower socioeconomic status (R2 = 25.9%). Poorer performance on the speed and attention domain was predicted by younger age at follow-up (R2 = 53.5%). Poorer verbal memory was predicted by lower birth weight, younger age at follow-up, and greater exposure to acidotic events (R2 = 50.6%). The machine learning models did not reveal added value in terms of model performance as compared to linear regression. CONCLUSION: The findings of this study suggest that in children with previous PICU admission for bronchiolitis, (1) lower birth weight, younger age at follow-up, and lower socioeconomic status are associated with poorer neurocognitive outcome; and (2) greater exposure to acidotic events during PICU admission is associated with poorer verbal memory outcome. The findings of this study provide no evidence for the added value of machine learning models as compared to linear regression analysis in the prediction of long-term neurocognitive outcome in a relatively small sample of children. WHAT IS KNOWN: • Adverse neurocognitive outcomes are described in PICU survivors, which are known to interfere with development in other major domains of functioning, such as mental health, academic achievement, and socioeconomic success, highlighting neurocognition as an important outcome after PICU admission. • Machine learning is a rapidly growing field of artificial intelligence that is increasingly applied in health care settings, with great potential to capture the complexity of outcome prediction. WHAT IS NEW: • This study shows that lower birth weight, lower socioeconomic status, and greater exposure to acidotic events during PICU admission for bronchiolitis are associated with poorer long-term neurocognitive outcome after PICU admission. Results provide no evidence for the added value of machine learning models in a relatively small sample of children. • As bronchiolitis seldom manifests neurologically, the relation between acidotic events and neurocognitive outcome may reflect either potentially harmful effects of acidosis itself or related processes such as hypercapnia or hypoxic and/or ischemic events during PICU admission. This study further highlights the importance of structured follow-up to monitor long-term outcome of children after PICU admission.

Long-term outcomes of children after prenatal exposure to maternal cancer and its treatment.

The incidence of antenatal cancer is increasing, prompting a medical-ethical evaluation. The International Network on Cancer, Infertility, and Pregnancy (INCIP) was established to study cancer treatment safety during pregnancy and its impact on maternal and child health. Pivotal research has led to a paradigm shift in clinical management, demonstrating the feasibility and safety of most antenatal oncological treatments. Short-term outcomes reveal normal growth and cardiac function in the exposed offspring, but caution is advised against first-trimester chemotherapy. Psychological impact studies highlight the elevated levels of distress in pregnant cancer patients, underscoring the need for personalized information and ongoing psychological support. Long-term follow-up studies address gaps in postnatal impacts, while research into specific chemotherapeutic agents continues. Despite generally reassuring outcomes, continued monitoring is crucial, especially in families, such as those where the child was born premature after cancer (treatment) during pregnancy or where mothers are frequently absent due to continued illness or have died from. The ongoing INCIP child follow-up initiative aims to further elucidate knowledge gaps, emphasizing the importance of large-scale studies and personalized patient care.