The Philadelphia Neurodevelopmental Cohort (PNC) is a large-scale, NIMH funded initiative to understand how brain maturation mediates cognitive development and vulnerability to psychiatric illness, ...and understand how genetics impacts this process. As part of this study, 1445 adolescents ages 8–21 at enrollment underwent multimodal neuroimaging. Here, we highlight the conceptual basis for the effort, the study design, and the measures available in the dataset. We focus on neuroimaging measures obtained, including T1-weighted structural neuroimaging, diffusion tensor imaging, perfusion neuroimaging using arterial spin labeling, functional imaging tasks of working memory and emotion identification, and resting state imaging of functional connectivity. Furthermore, we provide characteristics regarding the final sample acquired. Finally, we describe mechanisms in place for data sharing that will allow the PNC to become a freely available public resource to advance our understanding of normal and pathological brain development.
•The PNC is a large-scale study of neurodevelopment, with 1445 subjects imaged.•Measures span multi-modal MRI, genomics, and testing of cognition and psychopathology.•The PNC will be a public resource to study normal and pathological brain development.
Sex differences in human behavior show adaptive complementarity: Males have better motor and spatial abilities, whereas females have superior memory and social cognition skills. Studies also show sex ...differences in human brains but do not explain this complementarity. In this work, we modeled the structural connectome using diffusion tensor imaging in a sample of 949 youths (aged 8—22 y, 428 males and 521 females) and discovered unique sex differences in brain connectivity during the course of development. Connection-wise statistical analysis, as well as analysis of regional and global network measures, presented a comprehensive description of network characteristics. In all supratentorial regions, males had greater within-hemispheric connectivity, as well as enhanced modularity and transitivity, whereas between-hemispheric connectivity and cross-module participation predominated in females. However, this effect was reversed in the cerebellar connections. Analysis of these changes developmentally demonstrated differences in trajectory between males and females mainly in adolescence and in adulthood. Overall, the results suggest that male brains are structured to facilitate connectivity between perception and coordinated action, whereas female brains are designed to facilitate communication between analytical and intuitive processing modes.
COVID-19 pandemic is a global calamity posing an unprecedented opportunity to study resilience. We developed a brief resilience survey probing self-reliance, emotion-regulation, ...interpersonal-relationship patterns and neighborhood-environment, and applied it online during the acute COVID-19 outbreak (April 6-15, 2020), on a crowdsourcing research website ( www.covid19resilience.org ) advertised through social media. We evaluated level of stress (worries) regarding COVID-19: (1) contracting, (2) dying from, (3) currently having, (4) family member contracting, (5) unknowingly infecting others with (6) experiencing significant financial burden following. Anxiety (GAD7) and depression (PHQ2) were measured. Totally, 3042 participants (n = 1964 females, age range 18-79, mean age = 39) completed the resilience and COVID-19-related stress survey and 1350 of them (mean age = 41, SD = 13; n = 997 females) completed GAD7 and PHQ2. Participants significantly endorsed more distress about family contracting COVID-19 (48.5%) and unknowingly infecting others (36%), than getting COVID-19 themselves (19.9%), p < 0.0005 covarying for demographics and proxy COVID-19 exposures like getting tested and knowing infected individuals. Patterns of COVID-19 related worries, rates of anxiety (GAD7 > 10, 22.2%) and depression (PHQ2 > 2, 16.1%) did not differ between healthcare providers and non-healthcare providers. Higher resilience scores were associated with lower COVID-19 related worries (main effect F
= 134.9; p < 0.00001, covarying for confounders). Increase in 1 SD on resilience score was associated with reduced rate of anxiety (65%) and depression (69%), across healthcare and non-healthcare professionals. Findings provide empirical evidence on mental health associated with COVID-19 outbreak in a large convenience sample, setting a stage for longitudinal studies evaluating mental health trajectories following COVID-19 pandemic.
Diffusion tensor imaging (DTI) is a well-established magnetic resonance imaging (MRI) technique used for studying microstructural changes in the white matter. As with many other imaging modalities, ...DTI images suffer from technical between-scanner variation that hinders comparisons of images across imaging sites, scanners and over time. Using fractional anisotropy (FA) and mean diffusivity (MD) maps of 205 healthy participants acquired on two different scanners, we show that the DTI measurements are highly site-specific, highlighting the need of correcting for site effects before performing downstream statistical analyses. We first show evidence that combining DTI data from multiple sites, without harmonization, may be counter-productive and negatively impacts the inference. Then, we propose and compare several harmonization approaches for DTI data, and show that ComBat, a popular batch-effect correction tool used in genomics, performs best at modeling and removing the unwanted inter-site variability in FA and MD maps. Using age as a biological phenotype of interest, we show that ComBat both preserves biological variability and removes the unwanted variation introduced by site. Finally, we assess the different harmonization methods in the presence of different levels of confounding between site and age, in addition to test robustness to small sample size studies.
•Significant site and scanner effects exist in DTI scalar maps.•Several multi-site harmonization methods are proposed.•ComBat performs the best at removing site effects in FA and MD.•Voxels associated with age in FA and MD are more replicable after ComBat.•ComBat is generalizable to other imaging modalities.
Since initial reports regarding the impact of motion artifact on measures of functional connectivity, there has been a proliferation of participant-level confound regression methods to limit its ...impact. However, many of the most commonly used techniques have not been systematically evaluated using a broad range of outcome measures. Here, we provide a systematic evaluation of 14 participant-level confound regression methods in 393 youths. Specifically, we compare methods according to four benchmarks, including the residual relationship between motion and connectivity, distance-dependent effects of motion on connectivity, network identifiability, and additional degrees of freedom lost in confound regression. Our results delineate two clear trade-offs among methods. First, methods that include global signal regression minimize the relationship between connectivity and motion, but result in distance-dependent artifact. In contrast, censoring methods mitigate both motion artifact and distance-dependence, but use additional degrees of freedom. Importantly, less effective de-noising methods are also unable to identify modular network structure in the connectome. Taken together, these results emphasize the heterogeneous efficacy of existing methods, and suggest that different confound regression strategies may be appropriate in the context of specific scientific goals.
•We evaluate 14 participant-level de-noising pipelines for functional connectivity.•Pipeline performance is markedly heterogeneous.•GSR minimizes the impact of motion but introduces distance dependence.•Censoring reduces motion and improves network identifiability.
Several recent reports in large, independent samples have demonstrated the influence of motion artifact on resting-state functional connectivity MRI (rsfc-MRI). Standard rsfc-MRI preprocessing ...typically includes regression of confounding signals and band-pass filtering. However, substantial heterogeneity exists in how these techniques are implemented across studies, and no prior study has examined the effect of differing approaches for the control of motion-induced artifacts. To better understand how in-scanner head motion affects rsfc-MRI data, we describe the spatial, temporal, and spectral characteristics of motion artifacts in a sample of 348 adolescents. Analyses utilize a novel approach for describing head motion on a voxelwise basis. Next, we systematically evaluate the efficacy of a range of confound regression and filtering techniques for the control of motion-induced artifacts. Results reveal that the effectiveness of preprocessing procedures on the control of motion is heterogeneous, and that improved preprocessing provides a substantial benefit beyond typical procedures. These results demonstrate that the effect of motion on rsfc-MRI can be substantially attenuated through improved preprocessing procedures, but not completely removed.
► We describe spatial, temporal, and spectral features of rsfc-MRI motion artifact. ► We show how these artifact features impact preprocessing choices. ► We systematically evaluate different confound regression and filtering techniques. ► Our optimized preprocessing approach minimizes rsfc-MRI motion artifact.
Developmental structural neuroimaging studies in humans have long described decreases in gray matter volume (GMV) and cortical thickness (CT) during adolescence. Gray matter density (GMD), a measure ...often assumed to be highly related to volume, has not been systematically investigated in development. We used T1 imaging data collected on the Philadelphia Neurodevelopmental Cohort to study age-related effects and sex differences in four regional gray matter measures in 1189 youths ranging in age from 8 to 23 years. Custom T1 segmentation and a novel high-resolution gray matter parcellation were used to extract GMD, GMV, gray matter mass (GMM; defined as GMD × GMV), and CT from 1625 brain regions. Nonlinear models revealed that each modality exhibits unique age-related effects and sex differences. While GMV and CT generally decrease with age, GMD increases and shows the strongest age-related effects, while GMM shows a slight decline overall. Females have lower GMV but higher GMD than males throughout the brain. Our findings suggest that GMD is a prime phenotype for the assessment of brain development and likely cognition and that periadolescent gray matter loss may be less pronounced than previously thought. This work highlights the need for combined quantitative histological MRI studies.
This study demonstrates that different MRI-derived gray matter measures show distinct age and sex effects and should not be considered equivalent but complementary. It is shown for the first time that gray matter density increases from childhood to young adulthood, in contrast with gray matter volume and cortical thickness, and that females, who are known to have lower gray matter volume than males, have higher density throughout the brain. A custom preprocessing pipeline and a novel high-resolution parcellation were created to analyze brain scans of 1189 youths collected as part of the Philadelphia Neurodevelopmental Cohort. A clear understanding of normal structural brain development is essential for the examination of brain-behavior relationships, the study of brain disease, and, ultimately, clinical applications of neuroimaging.
It has recently been reported (Van Dijk et al., 2011) that in-scanner head motion can have a substantial impact on MRI measurements of resting-state functional connectivity. This finding may be of ...particular relevance for studies of neurodevelopment in youth, confounding analyses to the extent that motion and subject age are related. Furthermore, while Van Dijk et al. demonstrated the effect of motion on seed-based connectivity analyses, it is not known how motion impacts other common measures of connectivity. Here we expand on the findings of Van Dijk et al. by examining the effect of motion on multiple types of resting-state connectivity analyses in a large sample of children and adolescents (n=456). Following replication of the effect of motion on seed-based analyses, we examine the influence of motion on graphical measures of network modularity, dual-regression of independent component analysis, as well as the amplitude and fractional amplitude of low frequency fluctuation. In the entire sample, subject age was highly related to motion. Using a subsample where age and motion were unrelated, we demonstrate that motion has marked effects on connectivity in every analysis examined. While subject age was associated with increased within-network connectivity even when motion was accounted for, controlling for motion substantially attenuated the strength of this relationship. The results demonstrate the pervasive influence of motion on multiple types functional connectivity analysis, and underline the importance of accounting for motion in studies of neurodevelopment.
► In children and adolescents, motion and age are highly related. ► Motion impacts multiple common measures of functional connectivity. ► Failure to account for motion may inflate estimates of the effect of age.
Several independent studies have demonstrated that small amounts of in-scanner motion systematically bias estimates of resting-state functional connectivity. This confound is of particular importance ...for studies of neurodevelopment in youth because motion is strongly related to subject age during this period. Critically, the effects of motion on connectivity mimic major findings in neurodevelopmental research, specifically an age-related strengthening of distant connections and weakening of short-range connections. Here, in a sample of 780 subjects ages 8–22, we re-evaluate patterns of change in functional connectivity during adolescent development after rigorously controlling for the confounding influences of motion at both the subject and group levels. We find that motion artifact inflates both overall estimates of age-related change as well as specific distance-related changes in connectivity. When motion is more fully accounted for, the prevalence of age-related change as well as the strength of distance-related effects is substantially reduced. However, age-related changes remain highly significant. In contrast, motion artifact tends to obscure age-related changes in connectivity associated with segregation of functional brain modules; improved preprocessing techniques allow greater sensitivity to detect increased within-module connectivity occurring with development. Finally, we show that subject’s age can still be accurately estimated from the multivariate pattern of functional connectivity even while controlling for motion. Taken together, these results indicate that while motion artifact has a marked and heterogeneous impact on estimates of connectivity change during adolescence, functional connectivity remains a valuable phenotype for the study of neurodevelopment.
•Motion artifact inflates distance-related changes in developmental connectivity.•Motion artifact obscures segregation of functional brain modules with age.•Even when controlling for motion, connectivity can predict age.
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