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A balanced excitation-inhibition ratio (E/I ratio) is critical for healthy brain function. Normative development of cortex-wide E/I ratio remains unknown. Here, we noninvasively estimate a putative marker of whole-cortex E/I ratio by fitting a large-scale biophysically plausible circuit model to resting-state functional MRI (fMRI) data. We first confirm that our model generates realistic brain dynamics in the Human Connectome Project. Next, we show that the estimated E/I ratio marker is sensitive to the gamma-aminobutyric acid (GABA) agonist benzodiazepine alprazolam during fMRI. Alprazolam-induced E/I changes are spatially consistent with positron emission tomography measurement of benzodiazepine receptor density. We then investigate the relationship between the E/I ratio marker and neurodevelopment. We find that the E/I ratio marker declines heterogeneously across the cerebral cortex during youth, with the greatest reduction occurring in sensorimotor systems relative to association systems. Importantly, among children with the same chronological age, a lower E/I ratio marker (especially in the association cortex) is linked to better cognitive performance. This result is replicated across North American (8.2 to 23.0 y old) and Asian (7.2 to 7.9 y old) cohorts, suggesting that a more mature E/I ratio indexes improved cognition during normative development. Overall, our findings open the door to studying how disrupted E/I trajectories may lead to cognitive dysfunction in psychopathology that emerges during youth., Competing Interests: Competing interests statement:The authors declare no competing interest.

Understanding how traumatic stress affects typical brain development during adolescence is critical to elucidate underlying mechanisms related to both maladaptive functioning and resilience after traumatic exposures. The current study aimed to map deviations from normative ranges of brain gray matter for youths with traumatic exposures. For each cortical and subcortical gray matter region, normative percentiles of variations were established using structural MRI from typically developing youths without any traumatic exposure (n = 245; age range = 8-23) from the Philadelphia Neurodevelopmental Cohort (PNC). The remaining PNC participants with neuroimaging data (n = 1129) were classified as either within the normative range (5-95%), delayed (>95%) or accelerated (<5%) maturational ranges for each region using the normative model. An averaged quantile regression index was calculated across all regions. Mediation models revealed that high traumatic stress load was positively associated with poorer cognitive functioning and greater psychopathology, and these associations were mediated by accelerated gray matter maturation. Furthermore, higher stressor reactivity scores, which represent a less resilient response under traumatic stress, were positively correlated with greater acceleration of gray matter maturation (r = 0.224, 95% CI = [0.17, 0.28], p < 0.001), suggesting that more accelerated maturation was linked to greater stressor response regardless of traumatic stress load. We conclude that traumatic stress is a source of deviation from normative brain development associated with poorer cognitive functioning and more psychopathology in the long run., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Psychiatric disorders are associated with cognitive dysfunction (CD), and reliable screening and follow-up of CD is essential both for research and clinical practice globally; yet, most assessments are in Western languages. We aimed to evaluate the test-retest reliability of the Turkish version of the Penn Computerized Neurocognitive Battery (PennCNB) to guide confident interpretation of results. Fifty-eight healthy individuals completed the PennCNB Turkish version in two sessions. After quality control, reliability analysis was conducted using Intraclass Correlation Coefficients (ICC), corrected for practice effects. Most measures were not significantly different between the sessions and had acceptable ICC values, with several exceptions. Scores were improved considerably for some memory measures, including immediate Facial Memory and Spatial Memory, and for incorrect responses in abstraction and mental flexibility, with correspondingly acceptable ICCs. Test-retest assessment of the Turkish version of the PennCNB shows that it can be used as a reliable real-time measurement of cognitive function in snapshot cross-sectional or longitudinal determinations. Preliminary validity assessment in this normative sample showed expected positive correlations with education level and negative correlations with age. Thus, the Turkish version of the PennCNB can be considered a reliable neuropsychological testing tool in research and clinical practice. Practice effects should be considered, especially when applied in short intervals. Significantly better performances in the retest, beyond practice effect, likely reflect nonlinear improvements in some participants who "learned how to learn" the memory tests or had insight on solving the abstraction and mental flexibility test.

Objective: Large-scale studies have revolutionized biomedical research, and neurocognitive tests can help elucidate the biological basis of neuropsychiatric diseases. However, studies have predominantly been conducted in Western settings. We describe the development and validation of a computerized battery (PennCNB) with the Xhosa population of South Africa., Method: Individuals with schizophrenia (n = 525) and a normative comparison group (n = 744) were balanced on age, sex, education, and region. Participants provided blood samples, were assessed psychiatrically, and were administered a PennCNB translation to isiXhosa, including measures of executive functions, episodic memory, complex cognition, social cognition, and sensorimotor speed. Feasibility was examined with test completion rates and input from administrators, and psychometric structural validity and associations with clinical and demographic characteristics were examined., Results: Tests were well tolerated by participants, as >87% had one (or fewer) test missing. Results suggested a similar factor structure to prior PennCNB studies in Western contexts, and expected age and sex effects were apparent. Furthermore, a similar profile of schizophrenia was observed, with neurocognitive deficits most pronounced for executive functions, especially attention, as well as memory, social cognition, and motor speed relative to complex cognition and sensorimotor speed., Conclusions: Results support the feasibility of implementing a culturally adapted computerized neurocognitive battery in sub-Saharan African settings and provide evidence supporting the concurrent validity of the translated instrument. Thus, the PennCNB is implementable on a large scale in non-Western contexts, shows expected factor structure, and can detect cognitive deficits associated with neuropsychiatric disorders. Obtaining valid measures of cognition by nonspecialized proctors is especially suitable in resource-limited settings, where traditional testing is prohibitive. Future work should establish normative standards, test-retest reliability, and sensitivity to treatment. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Introduction: Practice effects associated with the repeated administration of cognitive tests often confound true therapeutic or experimental effects. Alternate test forms help reduce practice effects, but generating stimulus sets with identical properties can be difficult. The main objective of this study was to disentangle practice and stimulus set effects for Cognition , a battery of 10 brief cognitive tests specifically designed for high-performing populations with 15 unique versions for repeated testing. A secondary objective was to investigate the effects of test-retest interval on practice effects., Methods: The 15 versions of Cognition were administered in three groups of 15-16 subjects (total N = 46, mean±SD age 32.5 ± 7.2 years, range 25-54 years, 23 male) in a randomized but balanced fashion with administration intervals of ≥10 days, ≤5 days, or 4 times per day. Mixed effect models were used to investigate linear and logarithmic trends across repeated administrations in key speed and accuracy outcomes, whether these trends differed significantly between administration interval groups, and whether stimulus sets differed significantly in difficulty., Results: Protracted, non-linear practice effects well beyond the second administration were observed for most of the 10 Cognition tests both in accuracy and speed, but test-retest administration interval significantly affected practice effects only for 3 out of the 10 tests and only in the speed domain. Stimulus set effects were observed for the 6 Cognition tests that use unique sets of stimuli. Factors were established that allow for correcting for both practice and stimulus set effects., Conclusions: Practice effects are pronounced and probably under-appreciated in cognitive testing. The correction factors established in this study are a unique feature of the Cognition battery that can help avoid masking practice effects, address noise generated by differences in stimulus set difficulty, and facilitate interpretation of results from studies with repeated assessments.

A diverse set of white matter connections supports seamless transitions between cognitive states. However, it remains unclear how these connections guide the temporal progression of large-scale brain activity patterns in different cognitive states. Here, we analyze the brain's trajectories across a set of single time point activity patterns from functional magnetic resonance imaging data acquired during the resting state and an n-back working memory task. We find that specific temporal sequences of brain activity are modulated by cognitive load, associated with age, and related to task performance. Using diffusion-weighted imaging acquired from the same subjects, we apply tools from network control theory to show that linear spread of activity along white matter connections constrains the probabilities of these sequences at rest, while stimulus-driven visual inputs explain the sequences observed during the n-back task. Overall, these results elucidate the structural underpinnings of cognitively and developmentally relevant spatiotemporal brain dynamics.

Background: Severe mental illness diagnoses have overlapping symptomatology and shared genetic risk, motivating cross-diagnostic investigations of disease-relevant quantitative measures. We analysed relationships between neurocognitive performance, symptom domains, and diagnoses in a large sample of people with severe mental illness not ascertained for a specific diagnosis (cases), and people without mental illness (controls) from a single, homogeneous population., Methods: In this case-control study, cases with severe mental illness were ascertained through electronic medical records at Clínica San Juan de Dios de Manizales (Manizales, Caldas, Colombia) and the Hospital Universitario San Vicente Fundación (Medellín, Antioquía, Colombia). Participants were assessed for speed and accuracy using the Penn Computerized Neurocognitive Battery (CNB). Cases had structured interview-based diagnoses of schizophrenia, bipolar 1, bipolar 2, or major depressive disorder. Linear mixed models, using CNB tests as repeated measures, modelled neurocognition as a function of diagnosis, sex, and all interactions. Follow-up analyses in cases included symptom factor scores obtained from exploratory factor analysis of symptom data as main effects., Findings: Between Oct 1, 2017, and Nov 1, 2019, 2406 participants (1689 cases [schizophrenia n=160; bipolar 1 disorder n=519; bipolar 2 disorder n=204; and major depressive disorder n=806] and 717 controls; mean age 39 years (SD 14); and 1533 female) were assessed. Participants with bipolar 1 disorder and schizophrenia had similar impairments in accuracy and speed across cognitive domains. Participants with bipolar 2 disorder and major depressive disorder performed similarly to controls, with subtle deficits in executive and social cognition. A three-factor model (psychosis, mania, and depression) best represented symptom data. Controlling for diagnosis, premorbid IQ, and disease severity, high lifetime psychosis scores were associated with reduced accuracy and speed across cognitive domains, whereas high depression scores were associated with increased social cognition accuracy., Interpretation: Cross-diagnostic investigations showed that neurocognitive function in severe mental illness is characterised by two distinct profiles (bipolar 1 disorder and schizophrenia, and bipolar 2 disorder and major depressive disorder), and is associated with specific symptom domains. These results suggest the utility of this design for elucidating severe mental illness causes and trajectories., Funding: US National Institute of Mental Health., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Brain iron is vital to multiple aspects of brain function, including oxidative metabolism, myelination, and neurotransmitter synthesis. Atypical iron concentration in the basal ganglia is associated with neurodegenerative disorders in aging and cognitive deficits. However, the normative development of brain iron concentration in adolescence and its relationship to cognition are less well understood. Here, we address this gap in a longitudinal sample of 922 humans aged 8-26 years at the first visit (M = 15.1, SD = 3.72; 336 males, 486 females) with up to four multiecho T2* scans each. Using this sample of 1236 imaging sessions, we assessed the longitudinal developmental trajectories of tissue iron in the basal ganglia. We quantified tissue iron concentration using R2* relaxometry within four basal ganglia regions, including the caudate, putamen, nucleus accumbens, and globus pallidus. The longitudinal development of R2* was modeled using generalized additive mixed models (GAMMs) with splines to capture linear and nonlinear developmental processes. We observed significant increases in R2* across all regions, with the greatest and most prolonged increases occurring in the globus pallidus and putamen. Further, we found that the developmental trajectory of R2* in the putamen is significantly related to individual differences in cognitive ability, such that greater cognitive ability is increasingly associated with greater iron concentration through late adolescence and young-adulthood. Together, our results suggest a prolonged period of basal ganglia iron enrichment that extends into the mid-twenties, with diminished iron concentration associated with poorer cognitive ability during late adolescence. SIGNIFICANCE STATEMENT Brain tissue iron is essential to healthy brain function. Atypical basal ganglia tissue iron levels have been linked to impaired cognition in iron deficient children and adults with neurodegenerative disorders. However, the normative developmental trajectory of basal ganglia iron concentration during adolescence and its association with cognition are less well understood. In the largest study of tissue iron development yet reported, we characterize the developmental trajectory of tissue iron concentration across the basal ganglia during adolescence and provide evidence that diminished iron content is associated with poorer cognitive performance even in healthy youth. These results highlight the transition from adolescence to adulthood as a period of dynamic maturation of tissue iron concentration in the basal ganglia., (Copyright © 2020 the authors.)

The protracted development of structural and functional brain connectivity within distributed association networks coincides with improvements in higher-order cognitive processes such as executive function. However, it remains unclear how white-matter architecture develops during youth to directly support coordinated neural activity. Here, we characterize the development of structure-function coupling using diffusion-weighted imaging and n -back functional MRI data in a sample of 727 individuals (ages 8 to 23 y). We found that spatial variability in structure-function coupling aligned with cortical hierarchies of functional specialization and evolutionary expansion. Furthermore, hierarchy-dependent age effects on structure-function coupling localized to transmodal cortex in both cross-sectional data and a subset of participants with longitudinal data ( n = 294). Moreover, structure-function coupling in rostrolateral prefrontal cortex was associated with executive performance and partially mediated age-related improvements in executive function. Together, these findings delineate a critical dimension of adolescent brain development, whereby the coupling between structural and functional connectivity remodels to support functional specialization and cognition., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

BACKGROUND: Cognition is a neurocognitive test battery created at the University of Pennsylvania and adapted by the National Aeronautics and Space Administration (NASA). It comprises 10 neurocognitive tests that examine multiple domains, and has been validated in a normative sample of STEM-educated adults and compared to NASA's WinSCAT battery. METHODS: The purpose of this study was to follow the original sample to assess Cognition and WinSCAT's test-retest reliability and age, sex, and test-retest interval effects on performance. RESULTS: Performance on both Cognition and WinSCAT decreased with age but improved with repeated administration due to practice effects, and men had higher scores than women on tasks that required vigilant attention, spatial reasoning, and risk-taking behaviors. Assessment of test-retest reliability showed intraclass coefficients for efficiency ranging from 0.417 to 0.810, reflecting the broad nature of constructs assessed by Cognition. DISCUSSION: Results largely matched predictions, with some counter-intuitive results for test-retest reliability interval. Lee G, Moore TM, Basner M, Nasrini J, Roalf DR, Ruparel K, Port AM, Dinges DF, Gur RC. Age, sex, and repeated measures effects on NASA's "Cognition" Test Battery in STEM educated adults. Aerosp Med Hum Perform. 2020; 91(1):18-25.

Background: Traumatic stressful events (TSEs) during childhood and adolescence are associated with increased risk for psychopathology and cognitive impairment. Aberrations in social cognition may contribute to the psychopathology risk. We examined performance differences on social cognitive measures between youths with high TSE exposure and no TSE exposure and how these effects vary in female and male individuals., Methods: The Philadelphia Neurodevelopmental Cohort investigates clinical and cognitive phenotypes in a U.S. youth (aged 8-21 years) community population. Here we compared performance in social cognition tasks between youths with high exposure (≥3 TSEs, n = 830) and youths with no exposure (n = 5202). Three social cognition tasks were analyzed: 1) age differentiation, 2) emotion identification (happy, sad, angry, fearful, or neutral), and 3) emotion intensity differentiation (happy, sad, angry, and fearful)., Results: A significant TSE group by sex interaction was observed in all social cognitive tasks. In the emotion identification task, male subjects with high traumatic stress exposure outperformed nonexposed male subjects; exposure did not affect performance in female subjects. In the emotion intensity differentiation task, female subjects with high traumatic stress exposure performed worse than nonexposed female subjects, with no difference in male subjects between exposure groups. Exploratory analyses revealed that sex differences were driven by improved identification of angry expressions in stress-exposed male subjects and poorer performance in differentiating intensity of happy expressions in stress-exposed female subjects., Conclusions: Exposure to high levels of early life traumatic stress was associated with sex-specific differences in social cognition. These findings might be related to the sex-specific patterns of psychopathology emerging during adolescence., (Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Importance: Substantial shifts in perception and policy regarding cannabis have recently occurred, with use of cannabis increasing while its perceived harm decreases. One possible risk of increased cannabis use is poorer cognitive functioning, especially in youth., Objective: To provide the first quantitative synthesis of the literature examining cannabis and cognitive functioning in adolescents and young adults (with a mean age of 26 years and younger)., Data Sources: PubMed, PsycInfo, Academic Search Premier, Scopus, and bibliographies of relevant reviews were searched for peer-reviewed, English-language studies from the date the databases began through May 2017., Study Selection: Consensus criteria were used to determine study inclusion through abstract and manuscript review., Data Extraction and Synthesis: This study followed Meta-analysis of Observational Studies in Epidemiology guidelines. Effect size estimates were calculated using multivariate mixed-effects models for cognitive functioning outcomes classified into 10 domains., Main Outcomes and Measures: Results from neurocognitive tests administered in cross-sectional studies were primary outcomes, and we examined the influence of a priori explanatory variables on variability in effect size., Results: Sixty-nine studies of 2152 cannabis users (mean [SD] age, 20.6 [2.8] years; 1472 [68.4%] male) and 6575 comparison participants with minimal cannabis exposure were included (mean [SD] age, 20.8 [3.4]; 3669 [55.8%] male). Results indicated a small overall effect size (presented as mean d) for reduced cognitive functioning associated with frequent or heavy cannabis use (d, -0.25; 95% CI, -0.32 to -0.17; P < .001). The magnitude of effect sizes did not vary by sample age or age at cannabis use onset. However, studies requiring an abstinence period longer than 72 hours (15 studies; n = 928) had an overall effect size (d, -0.08; 95% CI, -0.22 to 0.07) that was not significantly different from 0 and smaller than studies with less stringent abstinence criteria (54 studies; n = 7799; d, -0.30; 95% CI, -0.37 to -0.22; P = .01)., Conclusions and Relevance: Associations between cannabis use and cognitive functioning in cross-sectional studies of adolescents and young adults are small and may be of questionable clinical importance for most individuals. Furthermore, abstinence of longer than 72 hours diminishes cognitive deficits associated with cannabis use. Although other outcomes (eg, psychosis) were not examined in the included studies, results indicate that previous studies of cannabis in youth may have overstated the magnitude and persistence of cognitive deficits associated with use. Reported deficits may reflect residual effects from acute use or withdrawal. Future studies should examine individual differences in susceptibility to cannabis-associated cognitive dysfunction.

Microgravity and elevated levels of CO 2 are two common environmental stressors in spaceflight that may affect cognitive performance of astronauts. In this randomized, double-blind, crossover trial (SPACECOT), 6 healthy males (mean ± SD age: 41 ± 5 yr) were exposed to 0.04% (ambient air) and 0.5% CO 2 concentrations during 26.5-h periods of -12° head-down tilt (HDT) bed rest with a 1-wk washout period between exposures. Subjects performed the 10 tests of the Cognition Test Battery before and on average 0.1, 5.2, and 21.0 h after the initiation of HDT bed rest. HDT in ambient air induced a change in response strategy, with increased response speed (+0.19 SD; P = 0.0254) at the expense of accuracy (-0.19 SD; P = 0.2867), resulting in comparable cognitive efficiency. The observed effects were small and statistically significant for cognitive speed only. However, even small declines in accuracy can potentially cause errors during mission-critical tasks in spaceflight. Unexpectedly, exposure to 0.5% CO 2 reversed the response strategy changes observed under HDT in ambient air. This was possibly related to hypercapnia-induced cerebrovascular reactivity that favors cortical regions in general and the frontal cortex in particular, or to the CNS arousing properties of mildly to moderately increased CO 2 levels. There were no statistically significant time-in-CO 2 effects for any cognitive outcome. The small sample size and the small effect sizes are major limitations of this study and its findings. The results should not be generalized beyond the group of investigated subjects until they are confirmed by adequately powered follow-up studies. NEW & NOTEWORTHY Simulating microgravity with exposure to 21 h of -12° head-down tilt bed rest caused a change in response strategy on a range of cognitive tests, with a statistically significant increase in response speed at the expense of accuracy. Cognitive efficiency was not affected. The observed speed-accuracy tradeoff was small but may nevertheless be important for mission-critical tasks in spaceflight. Importantly, the change in response strategy was reversed by increasing CO 2 concentrations to 0.5%.

Background: Neuropsychological changes that may occur due to the environmental and psychological stressors of prolonged spaceflight motivated the development of the Cognition Test Battery. The battery was designed to assess multiple domains of neurocognitive functions linked to specific brain systems. Tests included in Cognition have been validated, but not in high-performing samples comparable to astronauts, which is an essential step toward ensuring their usefulness in long-duration space missions., Methods: We administered Cognition (on laptop and iPad) and the WinSCAT, counterbalanced for order and version, in a sample of 96 subjects (50% women; ages 25-56 yr) with at least a Master's degree in science, technology, engineering, or mathematics (STEM). We assessed the associations of age, sex, and administration device with neurocognitive performance, and compared the scores on the Cognition battery with those of WinSCAT. Confirmatory factor analysis compared the structure of the iPad and laptop administration methods using Wald tests., Results: Age was associated with longer response times (mean β = 0.12) and less accurate (mean β = -0.12) performance, women had longer response times on psychomotor (β = 0.62), emotion recognition (β = 0.30), and visuo-spatial (β = 0.48) tasks, men outperformed women on matrix reasoning (β = -0.34), and performance on an iPad was generally faster (mean β = -0.55). The WinSCAT appeared heavily loaded with tasks requiring executive control, whereas Cognition assessed a larger variety of neurocognitive domains., Discussion: Overall results supported the interpretation of Cognition scores as measuring their intended constructs in high performing astronaut analog samples.Moore TM, Basner M, Nasrini J, Hermosillo E, Kabadi S, Roalf DR, McGuire S, Ecker AJ, Ruparel K, Port AM, Jackson CT, Dinges DF, Gur RC. Validation of the Cognition Test Battery for spaceflight in a sample of highly educated adults. Aerosp Med Hum Perform. 2017; 88(10):937-946.

Background: Social cognition impairments in neurodevelopmental disorders impact functioning. Face processing is the most extensively studied aspect of social cognition, commonly indexing this construct in neuropsychiatric disorders compared with typically developing youths. Applying social cognition measures as a Research Domain Criteria concept in the clinical arena requires establishing cutoffs for intervention and identifying vulnerability for psychopathology across disorders. This can be accomplished by comparing extreme performers across multiple clinical symptom features., Methods: The Philadelphia Neurodevelopmental Cohort (N = 9498), a community sample of youths (8-21 years old), was assessed with a structured interview (Kiddie Schedule for Affective Disorders and Schizophrenia). The Penn Computerized Neurocognitive Battery was administered measuring accuracy and response time on Executive, Episodic Memory, Complex Cognition, and Social Cognition domains. We parsed participants by performance on social cognition into tertiles and examined their neurocognitive and clinical profiles., Results: The top social cognition group outperformed the bottom group in face memory and complex reasoning. Concerning symptoms, the top performing group did not differ from the middle group, but the bottom performing group had higher externalizing and psychosis symptoms. There were sex differences in social cognition and symptom profiles but no sex × performance or sex × diagnosis × domain interactions., Conclusions: Social cognition is supported by strong face memory and complex reasoning skills. Poor performance portends more severe externalizing and psychosis symptoms. That average performance is sufficient for normative symptomatology suggests that interventions aimed at ameliorating social cognition deficits, as measured here, could be effective in normalizing level of symptoms., (Copyright © 2017. Published by Elsevier Inc.)

Cannabis use in youth is rising and has been linked to deficits in cognitive functioning. However, cognitive findings have primarily been based on small samples of users seeking treatment, and few studies have evaluated cognition in occasional cannabis users. Here, we examined 4,568 adolescents and young adults (ages 14-21 years) drawn from the Philadelphia Neurodevelopmental Cohort, a prospective, population-based study. Participants were classified as cannabis Non-Users (n = 3,401), Occasional Users (twice per week or less; n = 940), or Frequent Users (>3 times per week; n = 227). Mixed-model analyses examined main effects of cannabis use and interactions between age and cannabis use on cognitive functioning. There was a significant interaction between cannabis group and age such that adolescent (but not young adult) Frequent Users performed worse than Non-Users on measures of executive control (p = .002). Earlier age of cannabis use was associated with worse performance in executive control in Occasional Users (p = .04). Unexpectedly, Occasional Users exhibited better executive control, memory, and social cognition than Non-Users (ps < .05). Although mild executive control deficits in adolescent frequent users and a relation between early cannabis initiation and cognitive performance are partially consistent with prior research, cognitive deficits were not found in other hypothesized domains in this community-based sample. Moreover, occasional cannabis users displayed equivalent or even slightly better executive control, social-cognitive, and memory abilities compared with nonusers, suggesting complex relationships between cannabis use and cognition in youth. Longitudinal studies with community samples are needed to identify variables affecting risk and resilience to cognitive deficits associated with cannabis. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Background: There is growing evidence that neurocognitive function may be an endophenotype for mood disorders. The goal of this study is to examine the specificity and familiality of neurocognitive functioning across the full range of mood disorder subgroups, including Bipolar I (BP-I), Bipolar II (BP-II), Major Depressive Disorders (MDD), and controls in a community-based family study., Methods: A total of 310 participants from 137 families with mood spectrum disorders (n=151) and controls (n=159) completed the University of Pennsylvania's Computerized Neurocognitive Battery (CNB) that assessed the accuracy and speed of task performance across five domains. Mixed effects regression models tested association and familiality., Results: Compared to those without mood disorders, participants with BP-I had increased accuracy in complex cognition, while participants with MDD were more accurate in emotion recognition. There was also a significant familial association for accuracy of complex cognition. Mood disorder subgroups did not differ in performance speed in any of the domains., Limitations: The small number of BP-I cases, and family size limited the statistical power of these analyses, and the cross-sectional assessment of neurocognitive function precluded our ability to determine whether performance precedes or post dates onset of disorder., Conclusions: This is one of the few community-based family studies of potential neurocognitive endophenotypes that includes the full range of mood disorder subgroups. There were few differences in neurocognitive function except enhanced accuracy in specific domains among those with BP-I and MDD. The differential findings across specific mood disorder subgroups substantiate their heterogeneity in other biologic and endophenotypic domains., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: The Penn Computerized Neurocognitive Battery (CNB) was designed to measure performance accuracy and speed on specific neurobehavioral domains using tests that were previously validated with functional neuroimaging. The goal of the present study was to evaluate the neuropsychological theory used to construct the CNB by confirming the factor structure of the tests composing it., Method: In a large community sample (N = 9,138; age range 8-21), we performed a correlated-traits confirmatory factor analysis (CFA) and multiple exploratory factor analyses (EFAs) on the 12 CNB measures of Efficiency (which combine Accuracy and Speed). We then performed EFAs of the Accuracy and Speed measures separately. Finally, we performed a confirmatory bifactor analysis of the Efficiency scores. All analyses were performed with Mplus using maximum likelihood estimation., Results: RESULTS strongly support the a priori theory used to construct the CNB, showing that tests designed to measure executive, episodic memory, complex cognition, and social cognition aggregate their loadings within these domains. When Accuracy and Speed were analyzed separately, Accuracy produced 3 reliable factors: executive and complex cognition, episodic memory, and social cognition, while speed produced 2 factors: tests that require fast responses and those where each item requires deliberation. The statistical "Fit" of almost all models described above was acceptable (usually excellent)., Conclusions: Based on the analysis from these large-scale data, the CNB offers an effective means for measuring the integrity of intended neurocognitive domains in about 1 hour of testing and is thus suitable for large-scale clinical and genomic studies., (PsycINFO Database Record (c) 2015 APA, all rights reserved.)

A balanced excitation-inhibition ratio (E/I ratio) is critical for healthy brain function. Normative development of cortex-wide E/I ratio remains unknown. Here, we noninvasively estimate a putative marker of whole-cortex E/I ratio by fitting a large-scale biophysically plausible circuit model to resting-state functional MRI (fMRI) data. We first confirm that our model generates realistic brain dynamics in the Human Connectome Project. Next, we show that the estimated E/I ratio marker is sensitive to the gamma-aminobutyric acid (GABA) agonist benzodiazepine alprazolam during fMRI. Alprazolam-induced E/I changes are spatially consistent with positron emission tomography measurement of benzodiazepine receptor density. We then investigate the relationship between the E/I ratio marker and neurodevelopment. We find that the E/I ratio marker declines heterogeneously across the cerebral cortex during youth, with the greatest reduction occurring in sensorimotor systems relative to association systems. Importantly, among children with the same chronological age, a lower E/I ratio marker (especially in the association cortex) is linked to better cognitive performance. This result is replicated across North American (8.2 to 23.0 y old) and Asian (7.2 to 7.9 y old) cohorts, suggesting that a more mature E/I ratio indexes improved cognition during normative development. Overall, our findings open the door to studying how disrupted E/I trajectories may lead to cognitive dysfunction in psychopathology that emerges during youth. [ABSTRACT FROM AUTHOR]

Background: Neuropsychiatric disorders are common in 22q11.2 Deletion Syndrome (22q11DS) with about 25% of affected individuals developing schizophrenia spectrum disorders by young adulthood. Longitudinal evaluation of psychosis spectrum features and neurocognition can establish developmental trajectories and impact on functional outcome. Methods: 157 youth with 22q11DS were assessed longitudinally for psychopathology focusing on psychosis spectrum symptoms, neurocognitive performance and global functioning. We contrasted the pattern of positive and negative psychosis spectrum symptoms and neurocognitive performance differentiating those with more prominent Psychosis Spectrum symptoms (PS+) to those without prominent psychosis symptoms (PS−). Results: We identified differences in the trajectories of psychosis symptoms and neurocognitive performance between the groups. The PS+ group showed age associated increase in symptom severity, especially negative symptoms and general nonspecific symptoms. Correspondingly, their level of functioning was worse and deteriorated more steeply than the PS− group. Neurocognitive performance was generally comparable in PS+ and PS− groups and demonstrated a similar age-related trajectory. However, worsening executive functioning distinguished the PS+ group from PS− counterparts. Notably, of the three executive function measures examined, only working memory showed a significant difference between the groups in rate of change. Finally, structural equation modeling showed that neurocognitive decline drove the clinical change. Conclusions: Youth with 22q11DS and more prominent psychosis features show worsening of symptoms and functional decline driven by neurocognitive decline, most related to executive functions and specifically working memory. The results underscore the importance of working memory in the developmental progression of psychosis. [ABSTRACT FROM AUTHOR]

Importance: Psychiatric and cognitive phenotypes have been associated with a range of specific, rare copy number variants (CNVs). Moreover, IQ is strongly associated with CNV risk scores that model the predicted risk of CNVs across the genome. But the utility of CNV risk scores for psychiatric phenotypes has been sparsely examined.Objective: To determine how CNV risk scores, common genetic variation indexed by polygenic scores (PGSs), and environmental factors combine to associate with cognition and psychopathology in a community sample.Design, Setting, and Participants: The Philadelphia Neurodevelopmental Cohort is a community-based study examining genetics, psychopathology, neurocognition, and neuroimaging. Participants were recruited through the Children's Hospital of Philadelphia pediatric network. Participants with stable health and fluency in English underwent genotypic and phenotypic characterization from November 5, 2009, through December 30, 2011. Data were analyzed from January 1 through July 30, 2021.Exposures: The study examined (1) CNV risk scores derived from models of burden, predicted intolerance, and gene dosage sensitivity; (2) PGSs from genomewide association studies related to developmental outcomes; and (3) environmental factors, including trauma exposure and neighborhood socioeconomic status.Main Outcomes and Measures: The study examined (1) neurocognition, with the Penn Computerized Neurocognitive Battery; (2) psychopathology, with structured interviews based on the Schedule for Affective Disorders and Schizophrenia for School-Age Children; and (3) brain volume, with magnetic resonance imaging.Results: Participants included 9498 youths aged 8 to 21 years; 4906 (51.7%) were female, and the mean (SD) age was 14.2 (3.7) years. After quality control, 18 185 total CNVs greater than 50 kilobases (10 517 deletions and 7668 duplications) were identified in 7101 unrelated participants genotyped on Illumina arrays. In these participants, elevated CNV risk scores were associated with lower overall accuracy on cognitive tests (standardized β = 0.12; 95% CI, 0.10-0.14; P = 7.41 × 10-26); lower accuracy across a range of cognitive subdomains; increased overall psychopathology; increased psychosis-spectrum symptoms; and higher deviation from a normative developmental model of brain volume. Statistical models of developmental outcomes were significantly improved when CNV risk scores were combined with PGSs and environmental factors.Conclusions and Relevance: In this study, elevated CNV risk scores were associated with lower cognitive ability, higher psychopathology including psychosis-spectrum symptoms, and greater deviations from normative magnetic resonance imaging models of brain development. Together, these results represent a step toward synthesizing rare genetic, common genetic, and environmental factors to understand clinically relevant outcomes in youth. [ABSTRACT FROM AUTHOR]

The brain is organized into networks at multiple resolutions, or scales, yet studies of functional network development typically focus on a single scale. Here, we derive personalized functional networks across 29 scales in a large sample of youths (n = 693, ages 8–23 years) to identify multi-scale patterns of network re-organization related to neurocognitive development. We found that developmental shifts in inter-network coupling reflect and strengthen a functional hierarchy of cortical organization. Furthermore, we observed that scale-dependent effects were present in lower-order, unimodal networks, but not higher-order, transmodal networks. Finally, we found that network maturation had clear behavioral relevance: the development of coupling in unimodal and transmodal networks are dissociably related to the emergence of executive function. These results suggest that the development of functional brain networks align with and refine a hierarchy linked to cognition. Studies of brain network development typically focus on a single scale. Here, the authors derived personalized functional networks across scales, and find that network development systematically adheres to and strengthens hierarchical cortical organization. [ABSTRACT FROM AUTHOR]

Childhood environments are critical in shaping cognitive neurodevelopment. With the increasing availability of large-scale neuroimaging datasets with deep phenotyping of childhood environments, we can now build upon prior studies that have considered relationships between one or a handful of environmental and neuroimaging features at a time. Here, we characterize the combined effects of hundreds of inter-connected and co-occurring features of a child's environment ("exposome") and investigate associations with each child's unique, multidimensional pattern of functional brain network organization ("functional topography") and cognition. We apply data-driven computational models to measure the exposome and define personalized functional brain networks in pre-registered analyses. Across matched discovery (n=5139, 48.5% female) and replication (n=5137, 47.1% female) samples from the Adolescent Brain Cognitive Development study, the exposome was associated with current (ages 9–10) and future (ages 11–12) cognition. Changes in the exposome were also associated with changes in cognition after accounting for baseline scores. Cross-validated ridge regressions revealed that the exposome is reflected in functional topography and can predict performance across cognitive domains. Importantly, a single measure capturing a child's exposome could more accurately and parsimoniously predict cognition than a wealth of personalized neuroimaging data, highlighting the importance of children's complex, multidimensional environments in cognitive neurodevelopment. • Complex childhood environments captured by the "exposome" are related to cognition. • Changes in the exposome are associated with changes in cognition over two years. • The exposome is reflected in personalized functional brain network organization. • Cross-validated ridge regressions trained on the exposome predict future cognition. [ABSTRACT FROM AUTHOR]

Environmental and psychological stressors can adversely affect astronaut cognitive performance in space. This study used a 6° head-down tilt bed rest (HDBR) paradigm to simulate some of the physiologic changes induced by microgravity. Twenty-four participants (mean ± SD age 33.3 ± 9.2 years, N = 16 men) spent 60 consecutive days in strict HDBR. They were studied in three groups of eight subjects each. One group served as Control, whereas the other two groups received either a continuous or intermittent artificial gravity (AG) countermeasure of 30 min centrifugation daily (1 g acceleration at the center of mass and 2 g at the feet). Participants performed all 10 tests of NASA's Cognition battery and a brief alertness and mood survey repeatedly before, during, and after the HDBR period. Test scores were adjusted for practice and stimulus set difficulty effects. A modest but statistically significant slowing across a range of cognitive domains was found in all three groups during HDBR compared to baseline, most consistently for sensorimotor speed, whereas accuracy was unaffected. These changes were observed early during HDBR and did not further worsen or improve with increasing time in HDBR, except for emotion recognition performance. With increasing time spent in HDBR, participants required longer time to decide which facial emotion was expressed. They were also more likely to select categories with negative valence over categories with neutral or positive valence. Except for workload, which was rated lower in the Control group, continuous or intermittent AG did not modify the effect of HDBR on cognitive performance or subjective responses. Participants expressed several negative survey responses during HDBR relative to baseline, and some of the responses further deteriorated during recovery, which highlights the importance of adequate medical and psychological support during extended duration HDBR studies. In conclusion, 60 days of HDBR were associated with moderate cognitive slowing and changes in emotion recognition performance, but these effects were not mitigated by either continuous or intermittent exposure to AG for 30 min daily. [ABSTRACT FROM AUTHOR]

Background. Questions remain regarding whether genetic influences on early life psychopathology overlap with cognition and show developmental variation. Methods. Using data from 9,421 individuals aged 8-21 from the Philadelphia Neurodevelopmental Cohort, factors of psychopathology were generated using a bifactor model of item-level data from a psychiatric interview. Five orthogonal factors were generated: anxious-misery (mood and anxiety), externalizing (attention deficit hyperactivity and conduct disorder), fear (phobias), psychosis-spectrum, and a general factor. Genetic analyses were conducted on a subsample of 4,662 individuals of European American ancestry. A genetic relatedness matrix was used to estimate heritability of these factors, and genetic correlations with executive function, episodic memory, complex reasoning, social cognition, motor speed, and general cognitive ability. Gene × Age analyses determined whether genetic influences on these factors show developmental variation. Results. Externalizing was heritable (h² = 0.46, p = 1 × 10-6), but not anxious-misery (h² = 0.09, p = 0.183), fear (h² = 0.04, p = 0.337), psychosis-spectrum (h² = 0.00, p = 0.494), or general psychopathology (h² = 0.21, p = 0.040). Externalizing showed genetic overlap with face memory (ρg =-0.412, p = 0.004), verbal reasoning (ρg =-0.485, p = 0.001), spatial reasoning (ρg =-0.426, p = 0.010), motor speed (ρg = 0.659, p = 1x10-4), verbal knowledge (ρg = -0.314, p = 0.002), and general cognitive ability (g)(ρg = -0.394, p = 0.002). Gene × Age analyses revealed decreasing genetic variance (γg = -0.146, p = 0.004) and increasing environmental variance (ρe = 0.059, p = 0.009) on externalizing. Conclusions. Cognitive impairment may be a useful endophenotype of externalizing psychopathology and, therefore, help elucidate its pathophysiological underpinnings. Decreasing genetic variance suggests that gene discovery efforts may be more fruitful in children than adolescents or young adults. [ABSTRACT FROM AUTHOR]

Background: Suicidal behavior is highly familial. Neurocognitive deficits have been proposed as an endophenotype for suicide risk that may contribute to the familial transmission of suicide. Yet, there is a lack of research on the neurocognitive functioning of first‐degree biological relatives of suicide attempters. The aim of the present study is to conduct the largest investigation to date of neurocognitive functioning in community youth with a family history of a fatal or nonfatal suicide attempt (FH). Methods: Participants aged 8–21 years from the Philadelphia Neurodevelopmental Cohort completed detailed clinical and neurocognitive evaluations. A subsample of 501 participants with a FH was matched to a comparison group of 3,006 participants without a family history of suicide attempt (no‐FH) on age, sex, race, and lifetime depression. Results: After adjusting for multiple comparisons and including relevant clinical and demographic covariates, youth with a FH had significantly lower executive function factor scores (F[1,3432] = 6.63, p =.010) and performed worse on individual tests of attention (F[1,3382] = 7.08, p =.008) and language reasoning (F[1,3387] = 5.12, p =.024) than no‐FH youth. Conclusions: Youth with a FH show small differences in executive function, attention, and language reasoning compared to youth without a FH. Further research is warranted to investigate neurocognitive functioning as an endophenotype for suicide risk. Implications for the prevention and treatment of suicidal behaviors are discussed. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Environmental and operational stressors commonly encountered in spaceflight can affect astronaut cognitive performance. It is currently unclear how performance decrements on test batteries that assess individual cognitive domains translate to complex operational performance. METHODS: N = 30 healthy adults (mean ± SD age 33.5 ± 7.1 yr, range 25–48 yr; 16 men) with demographic characteristics similar to astronauts performed all 10 tests of the Cognition test battery as well as a simulated 6 degrees-of-freedom (6df) spacecraft docking task 15 times. Performance on 60 Cognition outcome variables was rank-correlated with 6df docking performance individually as well as in models containing up to 12 predictors after accounting for sex, age, and study design effects. RESULTS: Average response time on the Digit Symbol Substitution Test (DSST)—a measure of processing speed requiring complex scanning, visual tracking, and working memory—was the best individual predictor of 6df docking performance (unadjusted = 5 20.550; semipartial cross-validated R² = 0.244). Furthermore, higher levels of spatial orientation efficiency and vigilant attention, lower levels of impulsivity, and faster response speed were associated with higher 6df performance, while sensorimotor speed, memory, and risk decision making were less relevant. After semipartial cross-validation, a model with three Cognition outcomes (DSST average response time, Abstract Matching accuracy, and conservative response bias on the Fractal 2-Back test) explained 30% of the variance in 6df performance. CONCLUSIONS: This study demonstrates direct links between performance on tests designed to assess specific cognitive domains and complex operational docking performance. [ABSTRACT FROM AUTHOR]

Aim: Few interventions address social cognition or functioning in individuals at clinical risk (CR) for psychosis. Theatre Improvisation Training to Promote Social Cognition (TIPS) is a manualized intervention based on drama therapy. We aim to describe TIPS, evaluate feasibility and acceptability, and present a preliminary investigation of outcomes in a quasi‐experimental design. Methods: Thirty‐six CR participants (15‐25 years) were ascertained from the Philadelphia Neurodevelopmental Cohort. Twenty‐six completed the TIPS protocol: 18 weekly 2‐hour group sessions led by a theatre director and actor‐assistant. Participants engaged in collaborative acting and improvisation exercises. Baseline and follow‐up assessments included the Clinical Assessment Interview for Negative Symptoms (CAINS), Structured Interview for Prodromal Syndromes, Global Assessment of Functioning (GAF) and Penn Computerized Neurocognitive Battery (CNB), which includes social cognitive tests. Acceptability was assessed using focus groups. Preliminary outcomes were compared to CR controls who were not enrolled in the study but completed follow‐up assessments using the same methods. Results: There were no significant differences in baseline demographics, psychosis symptoms, or cognition between those who did and did not complete the protocol. Overall, TIPS was considered feasible and acceptable among CR. Preliminary outcomes suggest that TIPS may be effective in improving positive and negative psychosis‐spectrum symptoms and GAF, but not performance on facial emotion processing. Conclusions: TIPS is a promising and acceptable intervention that may improve symptoms and functioning in CR while providing a framework for participants to develop more empowered and confident ways of relating to others. Larger randomized controlled trials investigating TIPS efficacy are warranted. [ABSTRACT FROM AUTHOR]

Background: Although there are extensive data on clinical psychopathology in youth with suicidal ideation, data are lacking regarding their neurocognitive function.Aims: To characterise the cognitive profile of youth with suicidal ideation in a community sample and evaluate gender differences and pubertal status effects.Method: Participants (N = 6151, age 11-21 years, 54.9% females) from the Philadelphia Neurodevelopmental Cohort, a non-help-seeking community sample, underwent detailed clinical evaluation. Cognitive phenotyping included executive functioning, episodic memory, complex reasoning and social cognitive functioning. We compared participants with suicidal ideation (N = 672) and without suicidal ideation (N = 5479). Regression models were employed to evaluate differences in cognitive performance and functional level, with gender and pubertal status as independent variables. Models controlled for lifetime depression or general psychopathology, and for covariates including age and socioeconomic status.Results: Youth with suicidal ideation showed greater psychopathology, poorer level of function but better overall neurocognitive performance. Greater functional impairment was observed in females with suicidal ideation (suicidal ideation × gender interaction, t = 3.091, P = 0.002). Greater neurocognition was associated with suicidal ideation post-puberty (suicidal ideation × puberty interaction, t = 3.057, P = 0.002). Exploratory analyses of specific neurocognitive domains showed that suicidal ideation-associated cognitive superiority was more prominent in post-pubertal males compared with females (Cohen's d = 0.32 and d = 0.11, respectively) across all cognitive domains.Conclusions: Suicidal ideation was associated with poorer functioning yet better cognitive performance, especially in post-pubertal males, as measured by a comprehensive cognitive battery. Findings point to gender and pubertal-status specificity in the relationship between suicidal ideation, cognition and function in youth.Declaration Of Interest: R.B. serves on the scientific board and reports stock ownership in 'Taliaz Health', with no conflict of interest relevant to this work. M.A.O. receives royalties for the commercial use of the Columbia-Suicide Severity Rating Scale from the Research Foundation for Mental Hygiene. Her family owns stock in Bristol-Myers Squibb. All other authors declare no potential conflict of interest. [ABSTRACT FROM AUTHOR]

Background: Traumatic stressors during childhood and adolescence are associated with psychopathology, mostly studied in the context of post-traumatic stress disorder (PTSD) and depression. We investigated broader associations of traumatic stress exposure with psychopathology and cognition in a youth community sample. Methods: The Philadelphia Neurodevelopmental Cohort (N = 9498) is an investigation of clinical and neurobehavioral phenotypes in a diverse (56% Caucasian, 33% African American, 11% other) US youth community population (aged 8–21). Participants were ascertained through children's hospital pediatric (not psychiatric) healthcare network in 2009–2011. Structured psychiatric evaluation included screening for lifetime exposure to traumatic stressors, and a neurocognitive battery was administered. Results: Exposure rate to traumatic stressful events was high (none, N = 5204; one, N = 2182; two, N = 1092; three or more, N = 830). Higher stress load was associated with increased psychopathology across all clinical domains evaluated: mood/anxiety (standardized β =.378); psychosis spectrum (β =.360); externalizing behaviors (β =.311); and fear (β =.256) (controlling for covariates, all p < 0.001). Associations remained significant controlling for lifetime PTSD and depression. Exposure to high-stress load was robustly associated with suicidal ideation and cannabis use (odds ratio compared with non-exposed 5.3 and 3.2, respectively, both p < 0.001). Among youths who experienced traumatic stress (N = 4104), history of assaultive trauma was associated with greater psychopathology and, in males, vulnerability to psychosis and externalizing symptoms. Stress load was negatively associated with performance on executive functioning, complex reasoning, and social cognition. Conclusions: Traumatic stress exposure in community non-psychiatric help-seeking youth is substantial, and is associated with more severe psychopathology and neurocognitive deficits across domains, beyond PTSD and depression. [ABSTRACT FROM AUTHOR]

Microgravity and elevated levels of CO2 are two common environmental stressors in spaceflight that may affect cognitive performance of astronauts. In this randomized, double-blind, crossover trial (SPACECOT), 6 healthy males (mean ± SD age: 41 ± 5 yr) were exposed to 0.04% (ambient air) and 0.5% CO2 concentrations during 26.5-h periods of 12° head-down tilt (HDT) bed rest with a 1-wk washout period between exposures. Subjects performed the 10 tests of the Cognition Test Battery before and on average 0.1, 5.2, and 21.0 h after the initiation of HDT bed rest. HDT in ambient air induced a change in response strategy, with increased response speed (+0.19 SD; P = 0.0254) at the expense of accuracy (-0.19 SD; P = 0.2867), resulting in comparable cognitive efficiency. The observed effects were small and statistically significant for cognitive speed only. However, even small declines in accuracy can potentially cause errors during mission-critical tasks in spaceflight. Unexpectedly, exposure to 0.5% CO2 reversed the response strategy changes observed under HDT in ambient air. This was possibly related to hypercapnia-induced cerebrovascular reactivity that favors cortical regions in general and the frontal cortex in particular, or to the CNS arousing properties of mildly to moderately increased CO2 levels. There were no statistically significant time-in-CO2 effects for any cognitive outcome. The small sample size and the small effect sizes are major limitations of this study and its findings. The results should not be generalized beyond the group of investigated subjects until they are confirmed by adequately powered follow-up studies. NEW & NOTEWORTHY Simulating microgravity with exposure to 21 h of 12° head-down tilt bed rest caused a change in response strategy on a range of cognitive tests, with a statistically significant increase in response speed at the expense of accuracy. Cognitive efficiency was not affected. The observed speed-accuracy tradeoff was small but may nevertheless be important for mission-critical tasks in spaceflight. Importantly, the change in response strategy was reversed by increasing CO2 concentrations to 0.5%. [ABSTRACT FROM AUTHOR]

PTSD has been associated consistently with abnormalities in fear acquisition and extinction learning and retention. Fear acquisition refers to learning to discriminate between threat and safety cues. Extinction learning reflects the formation of a new inhibitory-memory that competes with a previously learned threat-related memory. Adjudicating the competition between threat memory and the new inhibitory memory during extinction may rely, in part, on cognitive processes such as working memory (WM). Despite significant shared neural circuits and signaling pathways the relationship between WM, fear acquisition, and extinction is poorly understood. Here, we analyzed data from a large sample of healthy Marines who underwent an assessment battery including tests of fear acquisition, extinction learning, and WM (N-back). Fear potentiated startle (FPS), fear expectancy ratings, and self-reported anxiety served as the primary dependent variables. High WM ability (N = 192) was associated with greater CS + fear inhibition during the late block of extinction and greater US expectancy change during extinction learning compared to individuals with low WM ability (N = 204). WM ability was not associated with magnitude of fear conditioning/expression. Attention ability was unrelated to fear acquisition or extinction supporting specificity of WM associations with extinction. These results support the conclusion that individual differences in WM may contribute to regulating fear responses. [ABSTRACT FROM AUTHOR]

Background: Validated screening tools are needed to detect subtle cognitive impairment in individuals at-risk for developing psychosis. Here, the utility of the Mini-Mental Status Examination (MMSE) and Penn Computerized Neurocognitive Battery (CNB) were evaluated for detecting cognitive impairment in individuals with psychosis spectrum (PS) symptoms.Methods: Participants (n = 229; 54 % female) completed the MMSE and CNB at baseline and two-year follow-up. PS (n = 91) and typically developing (TD; n = 138) participants were enrolled at baseline based on the presence or absence of PS symptoms. After two years, 65 participants remained PS, 104 participants remained TD, 23 participants had Emergent (EP) subthreshold PS symptoms, and 37 participants were experiencing Other Psychopathology (OP).Results: Generally, those with PS had lower scores than TD on both the MMSE (p < 0.0001) and CNB (p < 0.0001). Additionally, OP participants performed lower on the MMSE than TD (p = 0.02). Receiver operating characteristic (ROC) analyses indicated similar area under the curve (AUCs) for the two instruments (0.67); the MMSE showed higher specificity (0.71 vs. 0.62), while the CNB showed higher sensitivity (0.66 vs 0.52). Use of the MMSE and CNB in combination provided the highest diagnostic classification.Conclusion: The MMSE and CNB can be used to screen for cognitive impairment in PS. The MMSE is better at ruling out PS-related cognitive impairment while the CNB is better at ruling in PS-related cognitive impairment. Overall, our results indicate that both tests are useful in screening for cognitive impairment, particularly in combination, in a PS population. [ABSTRACT FROM AUTHOR]

Little is known about the impact of family history of psychosis on youth from community samples. To fill this gap, we compared youth with a first-degree relative with psychosis spectrum symptoms (i.e. family history of psychosis spectrum symptoms, FHPS) to youth without FHPS in a cross-sectional analysis of the Philadelphia Neurodevelopmental Cohort (PNC). The PNC is a racially diverse community sample of 9498 youth ages 8-21 years old, of whom 8928 completed the Family Interview for Genetic Studies to determine FHPS status. Polygenic risk score for schizophrenia (PRSS) was available for a subsample of 4433 European Americans. FHPS youth (n = 489) constituted 5.5% of the analytic sample. After adjusting for environmental risk factors (sociodemographic variables and traumatic stressful events), FHPS youth had lower functioning on the Children's Global Assessment Scale and elevated psychosis spectrum, mood, externalizing, and fear symptoms compared to non-FHPS youth (all p < .001). In the European-American subsample, FHPS status was associated with poorer functioning and greater symptom burden in all four psychopathology domains (all p < .001), even after covarying for PRSS. Thus, ascertaining FHPS is important because it is uniquely associated with symptoms and functional impairment in community youth beyond PRS-S and the environmental risk factors we investigated. Future research identifying environmental causes of FHPS-associated impairment could inform the development of interventions for the broad array of symptoms observed in FHPS youth. [ABSTRACT FROM AUTHOR]

The spatial distribution of large-scale functional networks on the cerebral cortex differs between individuals and is particularly variable in association networks that are responsible for higher-order cognition. However, it remains unknown how this functional topography evolves in development and supports cognition. Capitalizing on advances in machine learning and a large sample imaged with 27 min of high-quality functional MRI (fMRI) data (n = 693, ages 8–23 years), we delineate how functional topography evolves during youth. We found that the functional topography of association networks is refined with age, allowing accurate prediction of unseen individuals' brain maturity. The cortical representation of association networks predicts individual differences in executive function. Finally, variability of functional topography is associated with fundamental properties of brain organization, including evolutionary expansion, cortical myelination, and cerebral blood flow. Our results emphasize the importance of considering the plasticity and diversity of functional neuroanatomy during development and suggest advances in personalized therapeutics. • Functional topography is most variable in association cortex in youth • Functional topography is refined during youth and encodes brain maturity • Association network functional topography predicts executive function Cui et al. demonstrate that individual-specific functional networks are refined during youth in humans. Furthermore, the functional topography of association networks predicts individual differences in executive function. [ABSTRACT FROM AUTHOR]