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1.
J Magn Reson Imaging ; 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32128914

RESUMO

BACKGROUND: Quantitative susceptibility mapping (QSM) uses prior information to reconstruct maps, but prior information may not show pathology and introduce inconsistencies with susceptibility maps, degrade image quality and inadvertently smoothing image features. PURPOSE: To develop a local field data-driven QSM reconstruction that does not depend on spatial edge prior information. STUDY TYPE: Retrospective. SUBJECTS, ANIMAL MODELS: A dataset from 2016 ISMRM QSM Challenge, 11 patients with glioblastoma, a patient with microbleeds and porcine heart. SEQUENCE/FIELD STRENGTH: 3D gradient echo sequence on 3T and 7T scanners. ASSESSMENT: Accuracy was compared to Calculation of Susceptibility through Multiple Orientation Sampling (COSMOS), and several published techniques using region of interest (ROI) measurements, root-mean-squared error (RMSE), structural similarity index metric (SSIM), and high-frequency error norm (HFEN). Numerical ranking and semiquantitative image grading was performed by three expert observers to assess overall image quality (IQ) and image sharpness (IS). STATISTICAL TESTS: Bland-Altman, Friedman test, and Conover multiple comparisons. RESULTS: Loss adaptive dipole inversion (LADI) (ß = 0.82, R2 = 0.96), morphology-enabled dipole inversion (MEDI) (ß = 0.91, R2 = 0.97), and fast nonlinear susceptibility inversion (FANSI) (ß = 0.81, R2 = 0.98) had excellent correlation with COSMOS and no bias was detected (bias = 0.006 ± 0.014, P < 0.05). In glioblastoma patients, LADI showed consistently better performance (IQGrade = 2.6 ± 0.4, ISGrade = 2.6 ± 0.3, IQRank = 3.5 ± 0.4, ISRank = 3.9 ± 0.2) compared with MEDI (IQGrade = 2.1 ± 0.3, ISGrade = 2 ± 0.5, IQRank = 2.4 ± 0.5, ISRank = 2.8 ± 0.2) and FANSI (IQGrade = 2.2 ± 0.5, ISGrade = 2 ± 0.4, IQRank = 2.8 ± 0.3, ISRank = 2.1 ± 0.2). Dark artifact visible near the infarcted region in MEDI (InfMEDI = -0.27 ± 0.06 ppm) was better mitigated by FANSI (InfFANSI-TGV = -0.17 ± 0.05 ppm) and LADI (InfLADI = -0.18 ± 0.05 ppm). CONCLUSION: For neuroimaging applications, LADI preserved image sharpness and fine features in glioblastoma and microbleed patients. LADI performed better at mitigating artifacts in cardiac QSM. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY STAGE: 1.

2.
Elife ; 92020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32216874

RESUMO

Executive function develops during adolescence, yet it remains unknown how structural brain networks mature to facilitate activation of the fronto-parietal system, which is critical for executive function. In a sample of 946 human youths (ages 8-23y) who completed diffusion imaging, we capitalized upon recent advances in linear dynamical network control theory to calculate the energetic cost necessary to activate the fronto-parietal system through the control of multiple brain regions given existing structural network topology. We found that the energy required to activate the fronto-parietal system declined with development, and the pattern of regional energetic cost predicts unseen individuals' brain maturity. Finally, energetic requirements of the cingulate cortex were negatively correlated with executive performance, and partially mediated the development of executive performance with age. Our results reveal a mechanism by which structural networks develop during adolescence to reduce the theoretical energetic costs of transitions to activation states necessary for executive function.

3.
Menopause ; 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32187134

RESUMO

OBJECTIVE: Despite the fact that negative mood and executive dysfunction are common after risk-reducing salpingo-oophorectomy (RRSO), occurring in up to a third of women, little is known about risk factors predicting these negative outcomes. Adverse childhood experiences (ACE) predict poorer health in adulthood and may be a risk factor for negative outcomes after RRSO. Given the complex relationship between early life stress, affective disorders, and cognitive dysfunction, we hypothesized that ACE would be associated with poorer executive function and that mood symptoms would partially mediate this relationship. METHODS: Women who had undergone RRSO were included in the study (N = 552; age 30-73 y). We measured executive function (continuous performance task, letter n-back task, and Brown Attention Deficit Disorder Scale Score), exposure to early life stress (ACE questionnaire), and mood symptoms (Hospital Anxiety and Depression Scale). Generalized estimating equations were used to evaluate the association between ACE and executive dysfunction and the role of mood symptoms as a mediator in this relationship. RESULTS: ACE was associated with greater severity of subjective executive dysfunction (adjusted mean difference [aMD] = 7.1, P = 0.0005) and worse performance on both cognitive tasks (continuous performance task: aMD = -0.1, P = 0.03; n-back: aMD = -0.17, P = 0.007). Mood symptoms partially mediated ACE associations with sustained attention (21.3% mediated; 95% CI: 9.3%-100%) and subjective report of executive dysfunction (62.8% mediated; 95% CI: 42.3%-100%). CONCLUSIONS: The relationship between childhood adversity and executive dysfunction is partially mediated by mood symptoms. These data indicate that assessing history of childhood adversity and current anxiety and depression symptoms may play a role in treating women who report cognitive complaints after RRSO. : Video Summary:http://links.lww.com/MENO/A571.

4.
Am J Psychiatry ; : appiajp201919060583, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32046535

RESUMO

OBJECTIVE: 22q11.2 deletion syndrome (22q11DS) is among the strongest known genetic risk factors for schizophrenia. Previous studies have reported variable alterations in subcortical brain structures in 22q11DS. To better characterize subcortical alterations in 22q11DS, including modulating effects of clinical and genetic heterogeneity, the authors studied a large multicenter neuroimaging cohort from the ENIGMA 22q11.2 Deletion Syndrome Working Group. METHODS: Subcortical structures were measured using harmonized protocols for gross volume and subcortical shape morphometry in 533 individuals with 22q11DS and 330 matched healthy control subjects (age range, 6-56 years; 49% female). RESULTS: Compared with the control group, the 22q11DS group showed lower intracranial volume (ICV) and thalamus, putamen, hippocampus, and amygdala volumes and greater lateral ventricle, caudate, and accumbens volumes (Cohen's d values, -0.90 to 0.93). Shape analysis revealed complex differences in the 22q11DS group across all structures. The larger A-D deletion was associated with more extensive shape alterations compared with the smaller A-B deletion. Participants with 22q11DS with psychosis showed lower ICV and hippocampus, amygdala, and thalamus volumes (Cohen's d values, -0.91 to 0.53) compared with participants with 22q11DS without psychosis. Shape analysis revealed lower thickness and surface area across subregions of these structures. Compared with subcortical findings from other neuropsychiatric disorders studied by the ENIGMA consortium, significant convergence was observed between participants with 22q11DS with psychosis and participants with schizophrenia, bipolar disorder, major depressive disorder, and obsessive-compulsive disorder. CONCLUSIONS: In the largest neuroimaging study of 22q11DS to date, the authors found widespread alterations to subcortical brain structures, which were affected by deletion size and psychotic illness. Findings indicate significant overlap between 22q11DS-associated psychosis, idiopathic schizophrenia, and other severe neuropsychiatric illnesses.

5.
J Neurosci ; 40(9): 1810-1818, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-31988059

RESUMO

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.

6.
Biol Psychiatry ; 87(5): 473-482, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31690494

RESUMO

BACKGROUND: Internalizing disorders such as anxiety and depression are common psychiatric disorders that frequently begin in youth and exhibit marked heterogeneity in treatment response and clinical course. Given that symptom-based classification approaches do not align with underlying neurobiology, an alternative approach is to identify neurobiologically informed subtypes based on brain imaging data. METHODS: We used a recently developed semisupervised machine learning method (HYDRA [heterogeneity through discriminative analysis]) to delineate patterns of neurobiological heterogeneity within youths with internalizing symptoms using structural data collected at 3T from a sample of 1141 youths. RESULTS: Using volume and cortical thickness, cross-validation methods indicated 2 highly stable subtypes of internalizing youths (adjusted Rand index = 0.66; permutation-based false discovery rate p < .001). Subtype 1, defined by smaller brain volumes and reduced cortical thickness, was marked by impaired cognitive performance and higher levels of psychopathology than both subtype 2 and typically developing youths. Using resting-state functional magnetic resonance imaging and diffusion images not considered during clustering, we found that subtype 1 also showed reduced amplitudes of low-frequency fluctuations in frontolimbic regions at rest and reduced fractional anisotropy in several white matter tracts. In contrast, subtype 2 showed intact cognitive performance and greater volume, cortical thickness, and amplitudes during rest compared with subtype 1 and typically developing youths, despite still showing clinically significant levels of psychopathology. CONCLUSIONS: We identified 2 subtypes of internalizing youths differentiated by abnormalities in brain structure, function, and white matter integrity, with one of the subtypes showing poorer functioning across multiple domains. Identification of biologically grounded internalizing subtypes may assist in targeting early interventions and assessing longitudinal prognosis.

7.
Cereb Cortex ; 30(1): 1-19, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31220218

RESUMO

Higher socioeconomic status (SES) in childhood is associated with stronger cognitive abilities, higher academic achievement, and lower incidence of mental illness later in development. While prior work has mapped the associations between neighborhood SES and brain structure, little is known about the relationship between SES and intrinsic neural dynamics. Here, we capitalize upon a large cross-sectional community-based sample (Philadelphia Neurodevelopmental Cohort, ages 8-22 years, n = 1012) to examine associations between age, SES, and functional brain network topology. We characterize this topology using a local measure of network segregation known as the clustering coefficient and find that it accounts for a greater degree of SES-associated variance than mesoscale segregation captured by modularity. High-SES youth displayed stronger positive associations between age and clustering than low-SES youth, and this effect was most pronounced for regions in the limbic, somatomotor, and ventral attention systems. The moderating effect of SES on positive associations between age and clustering was strongest for connections of intermediate length and was consistent with a stronger negative relationship between age and local connectivity in these regions in low-SES youth. Our findings suggest that, in late childhood and adolescence, neighborhood SES is associated with variation in the development of functional network structure in the human brain.

8.
Proc Natl Acad Sci U S A ; 117(1): 771-778, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31874926

RESUMO

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.

9.
Aerosp Med Hum Perform ; 91(1): 18-25, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31852569

RESUMO

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.

10.
Neuropsychopharmacology ; 44(13): 2254-2262, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31476764

RESUMO

Irritability is an important dimension of psychopathology that spans multiple clinical diagnostic categories, yet its relationship to patterns of brain development remains sparsely explored. Here, we examined how transdiagnostic symptoms of irritability relate to the development of structural brain networks. All participants (n = 137, 83 females) completed structural brain imaging with 3 Tesla MRI at two timepoints (mean age at follow-up: 21.1 years, mean inter-scan interval: 5.2 years). Irritability at follow-up was assessed using the Affective Reactivity Index, and cortical thickness was quantified using Advanced Normalization Tools software. Structural covariance networks were delineated using non-negative matrix factorization, a multivariate analysis technique. Both cross-sectional and longitudinal associations with irritability at follow-up were evaluated using generalized additive models with penalized splines. The False Discovery Rate (q < 0.05) was used to correct for multiple comparisons. Cross-sectional analysis of follow-up data revealed that 11 of the 24 covariance networks were associated with irritability, with higher levels of irritability being associated with thinner cortex. Longitudinal analyses further revealed that accelerated cortical thinning within nine networks was related to irritability at follow-up. Effects were particularly prominent in brain regions implicated in emotion regulation, including the orbitofrontal, lateral temporal, and medial temporal cortex. Collectively, these findings suggest that irritability is associated with widespread reductions in cortical thickness and accelerated cortical thinning, particularly within the frontal and temporal cortex. Aberrant structural maturation of regions important for emotional regulation may in part underlie symptoms of irritability.

11.
Biometrics ; 75(4): 1145-1155, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31282994

RESUMO

Spatial extent inference (SEI) is widely used across neuroimaging modalities to adjust for multiple comparisons when studying brain-phenotype associations that inform our understanding of disease. Recent studies have shown that Gaussian random field (GRF)-based tools can have inflated family-wise error rates (FWERs). This has led to substantial controversy as to which processing choices are necessary to control the FWER using GRF-based SEI. The failure of GRF-based methods is due to unrealistic assumptions about the spatial covariance function of the imaging data. A permutation procedure is the most robust SEI tool because it estimates the spatial covariance function from the imaging data. However, the permutation procedure can fail because its assumption of exchangeability is violated in many imaging modalities. Here, we propose the (semi-) parametric bootstrap joint (PBJ; sPBJ) testing procedures that are designed for SEI of multilevel imaging data. The sPBJ procedure uses a robust estimate of the spatial covariance function, which yields consistent estimates of standard errors, even if the covariance model is misspecified. We use the methods to study the association between performance and executive functioning in a working memory functional magnetic resonance imaging study. The sPBJ has similar or greater power to the PBJ and permutation procedures while maintaining the nominal type 1 error rate in reasonable sample sizes. We provide an R package to perform inference using the PBJ and sPBJ procedures.

12.
Mol Psychiatry ; 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31358905

RESUMO

22q11.2 deletion syndrome (22q11DS)-a neurodevelopmental condition caused by a hemizygous deletion on chromosome 22-is associated with an elevated risk of psychosis and other developmental brain disorders. Prior single-site diffusion magnetic resonance imaging (dMRI) studies have reported altered white matter (WM) microstructure in 22q11DS, but small samples and variable methods have led to contradictory results. Here we present the largest study ever conducted of dMRI-derived measures of WM microstructure in 22q11DS (334 22q11.2 deletion carriers and 260 healthy age- and sex-matched controls; age range 6-52 years). Using harmonization protocols developed by the ENIGMA-DTI working group, we identified widespread reductions in mean, axial and radial diffusivities in 22q11DS, most pronounced in regions with major cortico-cortical and cortico-thalamic fibers: the corona radiata, corpus callosum, superior longitudinal fasciculus, posterior thalamic radiations, and sagittal stratum (Cohen's d's ranging from -0.9 to -1.3). Only the posterior limb of the internal capsule (IC), comprised primarily of corticofugal fibers, showed higher axial diffusivity in 22q11DS. 22q11DS patients showed higher mean fractional anisotropy (FA) in callosal and projection fibers (IC and corona radiata) relative to controls, but lower FA than controls in regions with predominantly association fibers. Psychotic illness in 22q11DS was associated with more substantial diffusivity reductions in multiple regions. Overall, these findings indicate large effects of the 22q11.2 deletion on WM microstructure, especially in major cortico-cortical connections. Taken together with findings from animal models, this pattern of abnormalities may reflect disrupted neurogenesis of projection neurons in outer cortical layers.

14.
Am J Psychiatry ; 176(12): 1000-1009, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31230463

RESUMO

OBJECTIVE: High comorbidity among psychiatric disorders suggests that they may share underlying neurobiological deficits. Abnormalities in cortical thickness and volume have been demonstrated in clinical samples of adults, but less is known when these structural differences emerge in youths. The purpose of this study was to examine the association between dimensions of psychopathology and brain structure. METHODS: The authors studied 1,394 youths who underwent brain imaging as part of the Philadelphia Neurodevelopmental Cohort. Dimensions of psychopathology were constructed using a bifactor model of symptoms. Cortical thickness and volume were quantified using high-resolution 3-T MRI. Structural covariance networks were derived using nonnegative matrix factorization and analyzed using generalized additive models with penalized splines to capture both linear and nonlinear age-related effects. RESULTS: Fear symptoms were associated with reduced cortical thickness in most networks, and overall psychopathology was associated with globally reduced gray matter volume across all networks. Structural covariance networks predicted psychopathology symptoms above and beyond demographic characteristics and cognitive performance. CONCLUSIONS: The results suggest a dissociable relationship whereby fear is most strongly linked to reduced cortical thickness and overall psychopathology is most strongly linked to global reductions in gray matter volume. Such results have implications for understanding how abnormalities of brain development may be associated with divergent dimensions of psychopathology.

15.
Psychol Assess ; 31(9): 1168-1173, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31192630

RESUMO

An important component of neuropsychological testing is assessment of premorbid intelligence to estimate a patient's ability independent of neurological impairment. A common test of premorbid IQ-namely, the Reading section of the Wide Range Achievement Test (WRAT)-has been shown to have high measurement error in the high ability range, is unnecessarily long (55 items), and is proprietary. We describe the development of an alternative, nonproprietary, computerized adaptive test for premorbid IQ, the Penn Reading Assessment (PRA-CAT). PRA-CAT items were calibrated using a 1-parameter item response theory model in a large community sample (N = 9,498), Ages 8 to 21, and the resulting parameters were used to simulate computerized adaptive testing sessions. Simulations demonstrated that the PRA-CAT achieves low measurement error (0.25; equivalent to Cronbach's alpha = .94) and acceptable measurement error (0.40; Cronbach's alpha = .84) after only 18 and 6 items, respectively (on average). Correlation of WRAT and PRA-CAT scores with numerous clinical, cognitive, demographic, and neuroimaging criteria suggests that validity of PRA-CAT score interpretation is comparable (and sometimes superior) with the WRAT. The fully functioning PRA-CAT for public use (including item parameter estimates reported here) has been built using the open-source program Concerto, and can be installed by anyone on a local computer or on the "cloud." Given the length and proprietary nature of the WRAT, the PRA-CAT shows promise as a potential alternative (and with minimal or no cost). Further validation in the context of neurological injury is needed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Testes de Inteligência , Testes Neuropsicológicos , Leitura , Adolescente , Adulto , Criança , Computadores , Feminino , Humanos , Masculino , Psicometria , Reprodutibilidade dos Testes , Adulto Jovem
16.
Neuropsychopharmacology ; 44(13): 2247-2253, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31112989

RESUMO

Social impairment occurs across the psychosis spectrum, but its pathophysiology remains poorly understood. Here we tested the hypothesis that reduced differential responses (aversive vs. neutral) in neural circuitry underpinning aversive conditioning of social stimuli characterizes the psychosis spectrum. Participants age 10-30 included a healthy control group (HC, analyzed n = 36) and a psychosis spectrum group (PSY, n = 71), including 49 at clinical risk for psychosis and 22 with a frank psychotic disorder. 3T fMRI utilized a passive aversive conditioning paradigm, with neutral faces as conditioned stimuli (CS) and a scream as the unconditioned stimulus. fMRI conditioning was indexed as the activation difference between aversive and neutral trials. Analysis focused on amygdala, ventromedial prefrontal cortex, and anterior insula, regions previously implicated in aversive and social-emotional processing. Ventromedial prefrontal cortex activated more to neutral than aversive CS; this "safety effect" was driven by HC and reduced in PSY, and correlated with subjective emotional ratings following conditioning. Insula showed the expected aversive conditioning effect, and although no group differences were found, its activation in PSY correlated with anxiety severity. Unexpectedly, amygdala did not show aversive conditioning; its activation trended greater for neutral than aversive CS, and did not differ significantly based on group or symptom severity. We conclude that abnormalities in social aversive conditioning are present across the psychosis spectrum including clinical risk, linked to a failure of safety processing. Aversive and safety learning provide translational paradigms yielding insight into pathophysiology of psychosis risk, and providing potential targets for therapeutic and preventative interventions.

17.
JAMA Psychiatry ; 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31141099

RESUMO

Importance: Low socioeconomic status (L-SES) and the experience of traumatic stressful events (TSEs) are environmental factors implicated in behavioral deficits, abnormalities in brain development, and accelerated maturation. However, the relative contribution of these environmental factors is understudied. Objective: To compare the association of L-SES and TSEs with psychopathology, puberty, neurocognition, and multimodal neuroimaging parameters in brain maturation. Design, Setting, and Participants: The Philadelphia Neurodevelopmental Cohort is a community-based study examining psychopathology, neurocognition, and neuroimaging among participants recruited through the Children's Hospital of Philadelphia pediatric network. Participants are youths aged 8 to 21 years at enrollment with stable health and fluency in English. The sample of 9498 participants was racially (5298 European ancestry [55.8%], 3124 African ancestry [32.9%], and 1076 other [11.4%]) and economically diverse. A randomly selected subsample (n = 1601) underwent multimodal neuroimaging. Data were collected from November 5, 2009, through December 30, 2011, and analyzed from February 1 through November 7, 2018. Main Outcomes and Measures: The following domains were examined: (1) clinical, including psychopathology, assessed with a structured interview based on the Schedule for Affective Disorders and Schizophrenia for School-Age Children, and puberty, assessed with the Tanner scale; (2) neurocognition, assessed by the Penn Computerized Neurocognitive Battery; and (3) multimodal magnetic resonance imaging parameters of brain structure and function. Results: A total of 9498 participants were included in the analysis (4906 [51.7%] female; mean [SD] age, 14.2 [3.7] years). Clinically, L-SES and TSEs were associated with greater severity of psychiatric symptoms across the psychopathology domains of anxiety/depression, fear, externalizing behavior, and the psychosis spectrum. Low SES showed small effect sizes (highest for externalizing behavior, 0.306 SD; 95% CI, 0.269 to 0.342), whereas TSEs had large effect sizes, with the highest in females for anxiety/depression (1.228 SD; 95% CI, 1.156 to 1.300) and in males for the psychosis spectrum (1.099 SD; 95% CI, 1.032 to 1.166). Both were associated with early puberty. Cognitively, L-SES had moderate effect sizes on poorer performance, the greatest being on complex cognition (-0.500 SD 95% CI, -0.536 to -0.464), whereas TSEs were associated with slightly better memory (0.129 SD; 95% CI, 0.084 to 0.174) and poorer complex reasoning (-0.109 SD; 95% CI, -0.154 to -0.064). Environmental factors had common and distinct associations with brain structure and function. Structurally, both were associated with lower volume, but L-SES had correspondingly lower gray matter density, whereas TSEs were associated with higher gray matter density. Functionally, both were associated with lower regional cerebral blood flow and coherence and with accelerated brain maturation. Conclusions and Relevance: Low SES and TSEs are associated with common and unique differences in symptoms, neurocognition, and structural and functional brain parameters. Both environmental factors are associated with earlier completion of puberty by physical features and brain parameters. These findings appear to underscore the need for identifying and preventing adverse environmental conditions associated with neurodevelopment.

18.
Mol Psychiatry ; 2019 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-30723287

RESUMO

Abnormalities in brain white matter (WM) are reported in youth at-risk for psychosis. Yet, the neurodevelopmental time course of these abnormalities remains unclear. Thus, longitudinal diffusion-weighted imaging (DWI) was used to investigate WM abnormalities in youth at-risk for psychosis. A subset of individuals from the Philadelphia Neurodevelopmental Cohort (PNC) completed two DWI scans approximately 20 months apart. Youths were identified through structured interview as having subthreshold persistent psychosis risk symptoms (n = 46), and were compared to healthy typically developing participants (TD; n = 98). Analyses were conducted at voxelwise and regional levels. Nonlinear developmental patterns were examined using penalized splines within a generalized additive model. Compared to TD, youth with persistent psychosis risk symptoms had lower whole-brain WM fractional anisotropy (FA) and higher radial diffusivity (RD). Voxelwise analyses revealed clusters of significant WM abnormalities within the temporal and parietal lobes. Lower FA within the cingulum bundle of hippocampus and cerebrospinal tracts were the most robust deficits in individuals with persistent psychosis symptoms. These findings were consistent over two visits. Thus, it appears that WM abnormalities are present early in youth with persistent psychosis risk symptoms, however, there is little evidence to suggest that these features emerge in late adolescence or early adulthood. Future studies should seek to characterize WM abnormalities in younger individuals and follow individuals as subthreshold psychotic symptoms emerge.

19.
Neuropsychopharmacology ; 44(8): 1362-1369, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30780151

RESUMO

Frequent cannabis use during adolescence has been associated with alterations in brain structure. However, studies have featured relatively inconsistent results, predominantly from small samples, and few studies have examined less frequent users to shed light on potential brain structure differences across levels of cannabis use. In this study, high-resolution T1-weighted MRIs were obtained from 781 youth aged 14-22 years who were studied as part of the Philadelphia Neurodevelopmental Cohort. This sample included 147 cannabis users (109 occasional [≤1-2 times per week] and 38 frequent [≥3 times per week] users) and 634 cannabis non-users. Several structural neuroimaging measures were examined in whole brain analyses, including gray and white matter volumes, cortical thickness, and gray matter density. Established procedures for stringent quality control were conducted, and two automated neuroimaging software processing packages were used to ensure robustness of results. There were no significant differences by cannabis group in global or regional brain volumes, cortical thickness, or gray matter density, and no significant group by age interactions were found. Follow-up analyses indicated that values of structural neuroimaging measures by cannabis group were similar across regions, and any differences among groups were likely of a small magnitude. In sum, structural brain metrics were largely similar among adolescent and young adult cannabis users and non-users. Our data converge with prior large-scale studies suggesting small or limited associations between cannabis use and structural brain measures in youth. Detailed studies of vulnerability to structural brain alterations and longitudinal studies examining long-term risk are clearly indicated.

20.
Cereb Cortex ; 29(5): 2102-2114, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29688290

RESUMO

Prematurity is associated with diverse developmental abnormalities, yet few studies relate cognitive and neurostructural deficits to a dimensional measure of prematurity. Leveraging a large sample of children, adolescents, and young adults (age 8-22 years) studied as part of the Philadelphia Neurodevelopmental Cohort, we examined how variation in gestational age impacted cognition and brain structure later in development. Participants included 72 preterm youth born before 37 weeks' gestation and 206 youth who were born at term (37 weeks or later). Using a previously-validated factor analysis, cognitive performance was assessed in three domains: (1) executive function and complex reasoning, (2) social cognition, and (3) episodic memory. All participants completed T1-weighted neuroimaging at 3 T to measure brain volume. Structural covariance networks were delineated using non-negative matrix factorization, an advanced multivariate analysis technique. Lower gestational age was associated with both deficits in executive function and reduced volume within 11 of 26 structural covariance networks, which included orbitofrontal, temporal, and parietal cortices as well as subcortical regions including the hippocampus. Notably, the relationship between lower gestational age and executive dysfunction was accounted for in part by structural network deficits. Together, these findings emphasize the durable impact of prematurity on cognition and brain structure, which persists across development.

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