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1.
Commun Biol ; 3(1): 261, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32444827

RESUMO

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.

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.
Psychiatry Res ; 285: 112783, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-32014626

RESUMO

A quantitative review of literature concerning olfactory function in 22q11.2 deletion syndrome (22q11DS) patients was performed detailing the scope/magnitude of deficits and probing possible moderators. We searched MEDLINE, EMBASE and PubMed to identify studies for inclusion. Effect sizes were based on differences in psychophysical olfactory tests between 22q11DS patients (n = 194) and typically developing comparison subjects (n = 466). 22q11DS patients exhibited marked olfactory dysfunction (d=-1.11, 95% CI=-1.29<δ<-0.92) that was homogeneous (p = 0.86). Diffuse olfactory deficits were seen which were not moderated by age or sex. 22q11DS patients exhibit large/diffuse deficits in olfactory function that are of a similar magnitude to observed neuropsychological impairments.

4.
Neuron ; 106(2): 340-353.e8, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32078800

RESUMO

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.

5.
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.

6.
J Autism Dev Disord ; 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31960263

RESUMO

Olfactory dysfunction is recognized in neurodevelopmental disorders and may serve as an early indicator of global dysfunction. The present meta-analysis measures olfaction effect sizes in attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASDs), and obsessive-compulsive disorder (OCD). Meta-analysis included 320 ADHD, 346 ASD, and 208 OCD individuals as compared to 910 controls. Olfactory performance deficits were small-to-moderate and heterogeneous (d = - 0.42, 95% CI = - 0.59 < δ < - 0.25). Meta-analytic results indicate that olfactory dysfunction is evident in individuals with ASD and OCD, with small-to-negligible effects in ADHD. These findings imply olfactory dysfunction is related to clinical phenotype in ASD and OCD, but not ADHD, and warrant inclusion in clinical assessment and evaluation of certain neurodevelopmental disorders.

7.
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.

8.
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.

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.
Proc Natl Acad Sci U S A ; 117(1): 771-778, 2020 01 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.


Assuntos
Desenvolvimento do Adolescente/fisiologia , Córtex Cerebral/crescimento & desenvolvimento , Cognição/fisiologia , Função Executiva/fisiologia , Rede Nervosa/fisiologia , Adolescente , Córtex Cerebral/diagnóstico por imagem , Criança , Conectoma , Estudos Transversais , Imagem de Tensor de Difusão , Feminino , Humanos , Estudos Longitudinais , Masculino , Análise Espacial , Adulto Jovem
11.
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.

12.
J Psychiatr Res ; 116: 26-33, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31176109

RESUMO

A substantial body of work supports the existence of a general psychopathology factor ("p"). Psychometrically, this is important because it implies that there is a psychological phenomenon (overall psychopathology) that can be measured and potentially used in clinical research or treatment. The present study aimed to construct, calibrate, and begin to validate a computerized adaptive (CAT) screener for "p". In a large community sample (N = 4544; age 11-21), we modeled 114 clinical items using a bifactor multidimensional item response theory (MIRT) model and constructed a fully functional (and public) CAT for assessing "p" called the Overall mental illness (OMI) screener. In a random, non-overlapping sample (N = 1019) with extended phenotyping (neuroimaging) from the same community cohort, adaptive versions of the OMI screener (10-, 20-, and 40-item) were simulated and compared to the full 114-item test in their ability to predict demographic characteristics, common mental disorders, and brain parameters. The OMI screener performed almost as well as the full test, despite being only a small fraction of the length. For prediction of 13 mental disorders, the mid-length (20-item) adaptive version showed mean area under the receiver operating characteristic curve of 0.76, compared to 0.79 for the full version. For prediction of brain parameters, mean absolute standardized relationship was 0.06 for the 20-item adaptive version, compared to 0.07 for the full form. This brief, public tool may facilitate the rapid and accurate measurement of overall psychopathology in large-scale studies and in clinical practice.

13.
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.

14.
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.

15.
Neuropsychol Rev ; 29(3): 328-337, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31144106

RESUMO

Olfactory dysfunction in epilepsy is well-documented in several olfactory domains. However, the clinical specificity of these deficits remains unknown. The aim of this systematic meta-analysis was to determine which domains of olfactory ability were most impaired in individuals with epilepsy, and to assess moderating factors affecting olfactory ability. Extant peer-reviewed literature on olfaction in epilepsy were identified via a computerized literature search using PubMed, MEDLINE, PsycInfo, and Google Scholar databases. Twenty-one articles met inclusion criteria. These studies included a total of 912 patients with epilepsy and 794 healthy comparison subjects. Included studies measured olfaction using tests of odor identification, discrimination, memory, and detection threshold in patients with different types of epilepsy, including temporal lobe epilepsy (TLE), mixed frontal epilepsy (M-F), and mixed epilepsy (MIX). Olfactory deficits were robust in patients with epilepsy when compared to healthy individuals, with effect sizes in the moderate to large range for several olfactory domains, including odor identification (d = -1.59), memory (d = -1.10), discrimination (d = -1.04), and detection threshold (d = -0.58). Olfactory deficits were most prominent in patients with TLE and M-F epilepsy. Amongst patients with epilepsy, sex, age, smoking status, education, handedness, and age of illness onset were significantly related to olfactory performance. Overall, these meta-analytic findings indicate that the olfactory system is compromised in epilepsy and suggest that detailed neurobiological investigations of the olfactory system may provide further insight into this disorder.

16.
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.

17.
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.

18.
Neuroimage ; 188: 122-134, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30508681

RESUMO

Executive function is a quintessential human capacity that emerges late in development and displays different developmental trends in males and females. Sex differences in executive function in youth have been linked to vulnerability to psychopathology as well as to behaviors that impinge on health, wellbeing, and longevity. Yet, the neurobiological basis of these differences is not well understood, in part due to the spatiotemporal complexity inherent in patterns of brain network maturation supporting executive function. Here we test the hypothesis that sex differences in impulsivity in youth stem from sex differences in the controllability of structural brain networks as they rewire over development. Combining methods from network neuroscience and network control theory, we characterize the network control properties of structural brain networks estimated from diffusion imaging data acquired in males and females in a sample of 879 youth aged 8-22 years. We summarize the control properties of these networks by estimating average and modal controllability, two statistics that probe the ease with which brain areas can drive the network towards easy versus difficult-to-reach states. We find that females have higher modal controllability in frontal, parietal, and subcortical regions while males have higher average controllability in frontal and subcortical regions. Furthermore, controllability profiles in males are negatively related to the false positive rate on a continuous performance task, a common measure of impulsivity. Finally, we find associations between average controllability and individual differences in activation during an n-back working memory task. Taken together, our findings support the notion that sex differences in the controllability of structural brain networks can partially explain sex differences in executive function. Controllability of structural brain networks also predicts features of task-relevant activation, suggesting the potential for controllability to represent context-specific constraints on network state more generally.


Assuntos
Encéfalo/fisiologia , Função Executiva/fisiologia , Comportamento Impulsivo/fisiologia , Modelos Neurológicos , Caracteres Sexuais , Adolescente , Criança , Feminino , Humanos , Masculino , Vias Neurais/fisiologia , Adulto Jovem
19.
J Cereb Blood Flow Metab ; 39(3): 524-535, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-29072856

RESUMO

The human brain consumes a disproportionate amount of the body's overall metabolic resources, and evidence suggests that brain and body may compete for substrate during development. Using perfusion MRI from a large cross-sectional cohort, we examined developmental changes of MRI-derived estimates of brain metabolism, in relation to weight change. Nonlinear models demonstrated that, in childhood, changes in body weight were inversely related to developmental age-related changes in brain metabolism. This inverse relationship persisted through early adolescence, after which body and brain metabolism began to decline. Females achieved maximum body growth approximately two years earlier than males, with a correspondingly earlier stabilization of brain metabolism to adult levels. These findings confirm prior findings with positron emission tomography performed in a much smaller cohort, demonstrate that relative brain metabolism can be inferred from noninvasive MRI data, and extend observations on the associations between body growth and brain metabolism to sex differences through adolescence.

20.
Hum Brain Mapp ; 40(7): 2033-2051, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-29091315

RESUMO

Motion artifacts are now recognized as a major methodological challenge for studies of functional connectivity. As in-scanner motion is frequently correlated with variables of interest such as age, clinical status, cognitive ability, and symptom severity, in-scanner motion has the potential to introduce systematic bias. In this article, we describe how motion-related artifacts influence measures of functional connectivity and discuss the relative strengths and weaknesses of commonly used denoising strategies. Furthermore, we illustrate how motion can bias inference, using a study of brain development as an example. Finally, we highlight directions of ongoing and future research, and provide recommendations for investigators in the field. Hum Brain Mapp, 40:2033-2051, 2019. © 2017 Wiley Periodicals, Inc.

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