How do tasks impact the reliability of fMRI functional connectivity?

While there is growing interest in the use of functional magnetic resonance imaging-functional connectivity (fMRI-FC) for biomarker research, low measurement reliability of conventional acquisitions may limit applications. Factors known to impact FC reliability include scan length, head motion, signal properties, such as temporal signal-to-noise ratio (tSNR), and the acquisition state or task. As tasks impact signal in a region-wise fashion, they likely impact FC reliability differently across the brain, making task an important decision in study design. Here, we use the densely sampled Midnight Scan Club (MSC) dataset, comprising 5 h of rest and 6 h of task fMRI data in 10 healthy adults, to investigate regional effects of tasks on FC reliability. We further considered how BOLD signal properties contributing to tSNR, that is, temporal mean signal (tMean) and temporal standard deviation (tSD), vary across the brain, associate with FC reliability, and are modulated by tasks. We found that, relative to rest, tasks enhanced FC reliability and increased tSD for specific task-engaged regions. However, FC signal variability and reliability is broadly dampened during tasks outside task-engaged regions. From our analyses, we observed signal variability was the strongest driver of FC reliability. Overall, our findings suggest that the choice of task can have an important impact on reliability and should be considered in relation to maximizing reliability in networks of interest as part of study design.

Factors Associated with Transition to Serious Mental Illness.

OBJECTIVE: There is increasing interest in early intervention and detection strategies for youth at-risk of developing a serious mental illness (SMI). Little is known about early factors that may be related to the later development of a SMI; thus, the aim of this study was to determine what clinical factors might relate to the development of in this study psychosis, bipolar disorder and severe or recurrent major depression in at-risk youth. METHOD: The sample consisted of 162 youth aged 12-26 years at different stages of risk. Thirty-one participants developed a SMI during the study. Those who made a transition were compared on a range of baseline clinical and functional measures with those who did not make the transition. A Cox regression model was used to assess the association between measures and later development of a SMI. RESULTS: Female sex, attenuated psychotic symptoms as assessed with the Scale of Psychosis-Risk Symptoms (SOPS) and ratings on the K-10 Distress Scale, were found to be significantly associated with the later transition to mental illness. Females were 2.77 times more likely to transition compared to males. For the SOPS and K-10 scales, there is a 14% increase in the transition rate relative to a one-scale increase in SOPS and a 7% increase in the transition rate relative to a one-point increase in the K-10. CONCLUSIONS: Results from these longitudinal data provide further insight into the specific clinical measures that may be pertinent in early detection of mental illnesses.

Structural brain network lateralization across childhood and adolescence.

Developmental lateralization of brain function is imperative for behavioral specialization, yet few studies have investigated differences between hemispheres in structural connectivity patterns, especially over the course of development. The present study compares the lateralization of structural connectivity patterns, or topology, across children, adolescents, and young adults. We applied a graph theory approach to quantify key topological metrics in each hemisphere including efficiency of information transfer between regions (global efficiency), clustering of connections between regions (clustering coefficient [CC]), presence of hub-nodes (betweenness centrality [BC]), and connectivity between nodes of high and low complexity (hierarchical complexity [HC]) and investigated changes in these metrics during development. Further, we investigated BC and CC in seven functionally defined networks. Our cross-sectional study consisted of 211 participants between the ages of 6 and 21 years with 93% being right-handed and 51% female. Global efficiency, HC, and CC demonstrated a leftward lateralization, compared to a rightward lateralization of BC. The sensorimotor, default mode, salience, and language networks showed a leftward asymmetry of CC. BC was only lateralized in the salience (right lateralized) and dorsal attention (left lateralized) networks. Only a small number of metrics were associated with age, suggesting that topological organization may stay relatively constant throughout school-age development, despite known underlying changes in white matter properties. Unlike many other imaging biomarkers of brain development, our study suggests topological lateralization is consistent across age, highlighting potential nonlinear mechanisms underlying developmental specialization.

Functional connectivity based brain signatures of behavioral regulation in children with ADHD, DCD, and ADHD-DCD.

Behavioral regulation problems have been associated with daily-life and mental health challenges in children with neurodevelopmental conditions such as attention-deficit/hyperactivity disorder (ADHD) and developmental coordination disorder (DCD). Here, we investigated transdiagnostic brain signatures associated with behavioral regulation. Resting-state fMRI data were collected from 115 children (31 typically developing (TD), 35 ADHD, 21 DCD, 28 ADHD-DCD) aged 7-17 years. Behavioral regulation was measured using the Behavior Rating Inventory of Executive Function and was found to differ between children with ADHD (i.e., children with ADHD and ADHD-DCD) and without ADHD (i.e., TD children and children with DCD). Functional connectivity (FC) maps were computed for 10 regions of interest and FC maps were tested for correlations with behavioral regulation scores. Across the entire sample, greater behavioral regulation problems were associated with stronger negative FC within prefrontal pathways and visual reward pathways, as well as with weaker positive FC in frontostriatal reward pathways. These findings significantly increase our knowledge on FC in children with and without ADHD and highlight the potential of FC as brain-based signatures of behavioral regulation across children with differing neurodevelopmental conditions.

Functional connectomes become more longitudinally self-stable, but not more distinct from others, across early childhood.

Functional connectomes, as measured with functional magnetic resonance imaging (fMRI), are highly individualized, and evidence suggests this individualization may increase across childhood. A connectome can become more individualized either by increasing self-stability or decreasing between-subject-similarity. Here we used a longitudinal early childhood dataset to investigate age associations with connectome self-stability, between-subject-similarity, and developmental individualization, defined as an individual's self-stability across a 12-month interval relative to their between-subject-similarity. fMRI data were collected during an 18-minute passive viewing scan from 73 typically developing children aged 4-7 years, at baseline and 12-month follow-up. We found that young children had highly individualized connectomes, with sufficient self-stability across 12-months for 98% identification accuracy. Linear models showed a significant relationship between age and developmental individualization across the whole brain and in most networks. This association appeared to be largely driven by an increase in self-stability with age, with only weak evidence for relationships between age and similarity across participants. Together our findings suggest that children's connectomes become more individualized across early childhood, and that this effect is driven by increasing self-stability rather than decreasing between-subject-similarity.

Childhood trauma and amygdala nuclei volumes in youth at risk for mental illness.

BACKGROUND: Adults with significant childhood trauma and/or serious mental illness may exhibit persistent structural brain changes within limbic structures, including the amygdala. Little is known about the structure of the amygdala prior to the onset of SMI, despite the relatively high prevalence of trauma in at-risk youth. METHODS: Data were gathered from the Canadian Psychiatric Risk and Outcome study. A total of 182 youth with a mean age of 18.3 years completed T1-weighted MRI scans along with clinical assessments that included questionnaires on symptoms of depression and anxiety. Participants also completed the Childhood Trauma and Abuse Scale. We used a novel subfield-specific amygdala segmentation workflow as a part of FreeSurfer 6.0 to examine amygdala structure. RESULTS: Participants with higher trauma scores were more likely to have smaller amygdala volumes, particularly within the basal regions. Among various types of childhood trauma, sexual and physical abuse had the largest effects on amygdala subregions. Abuse-related differences in the right basal region mediated the severity of depression and anxiety symptoms, even though no participants met criteria for clinical diagnosis at the time of assessment. CONCLUSION: The experience of physical or sexual abuse may leave detectable structural alterations in key regions of the amygdala, potentially mediating the risk of psychopathology in trauma-exposed youth.

Brain connectomes in youth at risk for serious mental illness: an exploratory analysis.

BACKGROUND: Identifying early biomarkers of serious mental illness (SMI)-such as changes in brain structure and function-can aid in early diagnosis and treatment. Whole brain structural and functional connectomes were investigated in youth at risk for SMI. METHODS: Participants were classified as healthy controls (HC; n = 33), familial risk for serious mental illness (stage 0; n = 31), mild symptoms (stage 1a; n = 37), attenuated syndromes (stage 1b; n = 61), or discrete disorder (transition; n = 9) based on clinical assessments. Imaging data was collected from two sites. Graph-theory based analysis was performed on the connectivity matrix constructed from whole-brain white matter fibers derived from constrained spherical deconvolution of the diffusion tensor imaging (DTI) scans, and from the correlations between brain regions measured with resting state functional magnetic resonance imaging (fMRI) data. RESULTS: Linear mixed effects analysis and analysis of covariance revealed no significant differences between groups in global or nodal metrics after correction for multiple comparisons. A follow up machine learning analysis broadly supported the findings. Several non-overlapping frontal and temporal network differences were identified in the structural and functional connectomes before corrections. CONCLUSIONS: Results suggest significant brain connectome changes in youth at transdiagnostic risk may not be evident before illness onset.

The death-implicit association test and suicide attempts: a systematic review and meta-analysis of discriminative and prospective utility.

Suicide risk assessment involves integrating patient disclosure of suicidal ideation and non-specific risk factors such as family history, past suicidal behaviour, and psychiatric symptoms. A death version of the implicit association test (D-IAT) has been developed to provide an objective measure of the degree to which the self is affiliated with life or death. However, this has inconsistently been associated with past and future suicidal behaviour. Here, we systematically review and quantitatively synthesize the literature examining the D-IAT and suicide attempts. We searched psychINFO, Medline, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception until 9 February 2021 to identify publications reporting D-IAT scores and suicide attempts (PROSPERO; CRD42020194394). Using random-effects models, we calculated standardized mean differences (SMD) and odds ratios (ORs) for retrospective suicide attempts. We then calculated ORs for future suicide attempts. ORs were dichotomized using a cutoff of zero representing equipoise between self-association with life and death. Eighteen studies met our inclusion criteria (n = 9551). The pooled SMD revealed higher D-IAT scores in individuals with a history of suicide attempt (SMD = 0.25, 95% CI 0.15 to 0.35); however, subgroup analyses demonstrated heterogeneity with acute care settings having lower effect sizes than community settings. Dichotomized D-IAT scores discriminated those with a history of suicide attempt from those without (OR 1.38 95% CI 1.01 to 1.89) and predicted suicide attempt over a six-month follow-up period (OR 2.99 95% CI 1.45 to 6.18; six studies, n = 781). The D-IAT may have a supplementary role in suicide risk assessment; however, determination of acute suicide risk and related clinical decisions should not be based solely on D-IAT performance.

Pre-reading language abilities and the brain's functional reading network in young children.

Early childhood is an important period for language development that lays the foundation for future reading abilities. However, little research has focused on the functional brain systems supporting pre-reading language abilities in typically developing children. Here, we investigated functional connectivity using passive viewing functional magnetic resonance imaging (fMRI) in 50 healthy children aged 2.85-5.07 years (3.84 â€‹± â€‹0.60 years, 22 female/28 male). Children completed the NEPSY-II Phonological Processing and Speeded Naming subtests and underwent fMRI while watching a movie of their choice. Functional connectivity was measured between key brain reading areas (bilateral angular gyrus, superior temporal gyrus, and inferior frontal gyrus) and the rest of the brain. Age-adjusted pre-reading scores positively correlated with functional connectivity between (1) the right angular gyrus and superior temporal gyrus, (2) the bilateral angular gyri and right pars triangularis and motor areas, (3) the left superior temporal gyrus and bilateral medial frontal gyrus and right cerebellum, (4) the left pars triangularis and middle occipital gyrus and insula, and (5) the right pars triangularis and the bilateral thalamus. Higher pre-reading scores were associated with stronger negative functional connectivity between (1) the left angular gyrus and auditory cortex, (2) the left superior temporal gyrus and occipital vision areas, (3) the right pars triangularis and medial frontal region, and (4) the right superior temporal gyrus and the posterior cingulate/precuneus. These results suggest better integration of the reading network, as well as its connections with other brain areas that support language or reading, and more dissociation between reading areas and the default mode network, in young children with better pre-reading skills. Our findings show that relationships between functional connectivity and pre-reading language skills are evident in young children even before formal reading instruction.

The effect of movie-watching on electroencephalographic responses to tactile stimulation.

Movie-watching is becoming a popular acquisition method to increase compliance and enable neuroimaging data collection in challenging populations such as children, with potential to facilitate studying the somatosensory system. However, relatively little is known about the possible crossmodal (audiovisual) influence of movies on cortical somatosensory processing. In this study, we examined the impact of dynamic audiovisual movies on concurrent cortical somatosensory processing using electroencephalography (EEG). Forty healthy young adults (18-25 years) received passive tactile fingertip stimulation while watching an "entertaining" movie and a novel "low-demand" movie called 'Inscapes' compared to eyes-open rest. Watching a movie did not modulate properties of early or late somatosensory-evoked potentials (SEPs). Similarly, no crossmodal influence on somatosensory adaptation, denoted by a reduction in SEP amplitude with repetitive tactile stimulation, was found. The prominent oscillatory responses in the alpha and beta frequency bands following tactile stimulation differed as a function of viewing condition, with stronger alpha/beta event-related desynchronization (ERD) during movie-watching compared to rest. These findings highlight that movie-watching is a valid acquisition method during which SEPs can be measured in basic research and clinical studies, but that the attentional demands of movies need to be taken into account when performing oscillatory analyses.

Early childhood development of white matter fiber density and morphology.

Early childhood is an important period for cognitive and brain development, though white matter changes specific to this period remain understudied. Here we utilize a novel analytic approach to quantify and track developmental changes in white matter micro- and macro-structure, calculated from individually oriented fiber-bundle populations, termed "fixels". Fixel-based analysis and mixed-effects models were used to assess tract-wise changes in fiber density and bundle morphology in 73 girls scanned at baseline (ages 4.09-7.02, mean â€‹= â€‹5.47, SD â€‹= â€‹0.81), 6-month (N â€‹= â€‹7), and one-year follow-up (N â€‹= â€‹42). For comparison, we also assessed changes in commonly utilized diffusion tensor metrics: fractional anisotropy (FA), and mean, radial and axial diffusivity (MD, RD, AD). Maturational increases in fixel-metrics were seen in most major white matter tracts, with the most rapid increases in the corticospinal tract and slowest or non-significant increases in the genu of the corpus callosum and uncinate fasciculi. As expected, we observed developmental increases in FA and decreases in MD, RD and AD, though percent changes were smaller relative to fixel-metrics. The majority of tracts showed more substantial morphological than microstructural changes. These findings highlight early childhood as a period of dynamic white matter maturation, characterized by large increases in macroscopic fiber bundle size, mild changes in axonal density, and parallel, albeit less substantial, changes in diffusion tensor metrics.

Maturation and interhemispheric asymmetry in neurite density and orientation dispersion in early childhood.

BACKGROUND: The brain's white matter undergoes profound changes during early childhood, which are believed to underlie the rapid development of cognitive and behavioral skills during this period. Neurite density, and complexity of axonal projections, have been shown to change across the life span, though changes during early childhood are poorly characterized. Here, we utilize neurite orientation dispersion and density imaging (NODDI) to investigate maturational changes in tract-wise neurite density index (NDI) and orientation dispersion index (ODI) during early childhood. Additionally, we assess hemispheric asymmetry of tract-wise NDI and ODI values, and longitudinal changes. METHODS: Two sets of diffusion weighted images with different diffusion-weighting were collected from 125 typically developing children scanned at baseline (N = 125; age range = 4.14-7.29; F/M = 73/52), 6-month (N = 8; F/M = 8/0), and 12-month (N = 52; F/M = 39/13) timepoints. NODDI and template-based tractography using constrained spherical deconvolution were utilized to calculate NDI and ODI values for major white matter tracts. Mixed-effects models controlling for sex, handedness, and in-scanner head motion were utilized to assess developmental changes in tract-wise NDI and ODI. Additional mixed-effects models were used to assess interhemispheric differences in tract-wise NDI and ODI values and hemispheric asymmetries in tract-wise development. RESULTS: Maturational increases in NDI were seen in all major white matter tracts, though we did not observe the expected tract-wise pattern of maturational rates (e.g. fast commissural/projection and slow frontal/temporal tract change). ODI did not change significantly with age in any tract. We observed greater NDI and ODI values in the right as compared to the left hemisphere for most tracts, but no hemispheric asymmetry for rate of change with age. CONCLUSIONS: These findings suggest that neurite density, but not orientation dispersion, increases with age during early childhood. In relation to NDI growth trends reported in infancy and late-childhood, our results suggest that early childhood may be a transitional period for neurite density maturation wherein commissural/projection fibers are approaching maturity, maturation in long range association fibers is increasing, and changes in limbic/frontal fibers remain modest. Rightward asymmetry in NDI and ODI values, but no asymmetry in developmental changes, suggests that rightward asymmetry of neurite density and orientation dispersion is established prior to age 4.

Reduced White Matter Fiber Density in Autism Spectrum Disorder.

Differences in brain networks and underlying white matter abnormalities have been suggested to underlie symptoms of autism spectrum disorder (ASD). However, robustly characterizing microstructural white matter differences has been challenging. In the present study, we applied an analytic technique that calculates structural metrics specific to differently-oriented fiber bundles within a voxel, termed "fixels". Fixel-based analyses were used to compare diffusion-weighted magnetic resonance imaging data from 25 individuals with ASD (mean age = 16.8 years) and 27 typically developing age-matched controls (mean age = 16.9 years). Group comparisons of fiber density (FD) and bundle morphology were run on a fixel-wise, tract-wise, and global white matter (GWM) basis. We found that individuals with ASD had reduced FD, suggestive of decreased axonal count, in several major white matter tracts, including the corpus callosum (CC), bilateral inferior frontal-occipital fasciculus, right arcuate fasciculus, and right uncinate fasciculus, as well as a GWM reduction. Secondary analyses assessed associations with social impairment in participants with ASD, and showed that lower FD in the splenium of the CC was associated with greater social impairment. Our findings suggest that reduced FD could be the primary microstructural white matter abnormality in ASD.

Trauma in Youth At-Risk for Serious Mental Illness.

Childhood trauma has been shown to have detrimental consequences on mental health. It is unknown what impact childhood trauma may have on the early trajectory of serious mental illness (SMI). The purpose of this article is to estimate the baseline prevalence, perceived impact, and duration of trauma that occurred before the age of 18 years in youth at risk for SMI using a transdiagnostic approach. This study included 243 youths, ages 12 to 25 years (42 healthy controls, 43 non-help-seeking individuals [stage 0], 52 help-seeking youth experiencing distress and possibly mild symptoms of anxiety or depression [stage1a], and 108 youth demonstrating attenuated symptoms of an SMI such as bipolar disorder or psychosis [stage 1b]). Participants completed an adapted version of the Childhood Trauma and Abuse scale. There were high frequencies of reported trauma across all stages. Symptomatic individuals experienced more trauma and bullying. Stage 1b individuals reported more physical abuse. Stage 1b also indicated psychological bullying to have a longer duration and impact on their lives. Future work should aim to clarify the complex interrelations between trauma and risk of SMI.

Functional magnetic resonance imaging study of working memory several years after pediatric concussion.

PRIMARY OBJECTIVE: The neurophysiological effects of pediatric concussion several years after injury remain inadequately characterized. The objective of this study was to determine if a history of concussion was associated with BOLD response differences during an n-back working memory task in youth. RESEARCH DESIGN: Observational, cross-sectional. METHODS AND PROCEDURES: Participants include 52 children and adolescents (M = 15.1 years, 95%CI = 14.4-15.8, range = 9-19) with past concussion (n = 33) or orthopedic injury (OI; n = 19). Mean time since injury was 2.5 years (95%CI = 2.0-3.0). Measures included postconcussion symptom ratings, neuropsychological testing, and blood-oxygen-dependent-level (BOLD) functional magnetic resonance imaging (fMRI) during an n-back working memory task. MAIN OUTCOMES AND RESULTS: Groups did not differ on accuracy or speed during the three n-back conditions. They also did not differ in BOLD signal change for the 1- vs. 0-back or 2- vs. 0-back contrasts (controlling for task performance). CONCLUSIONS: This study does not support group differences in BOLD response during an n-back working memory task in youth who are on average 2.5 years post-concussion. The findings are encouraging from the perspective of understanding recovery after pediatric concussion.

Aberrant limbic brain structures in young individuals at risk for mental illness.

AIM: Alterations in limbic structures may be present before the onset of serious mental illness, but whether subfield-specific limbic brain changes parallel stages in clinical risk is unknown. To address this gap, we compared the hippocampus, amygdala, and thalamus subfield-specific volumes in adolescents at various stages of risk for mental illness. METHODS: MRI scans were obtained from 182 participants (aged 12-25 years) from the Canadian Psychiatric Risk and Outcome study. The sample comprised of four groups: asymptomatic youth at risk due to family history of mental illness (Stage 0, n = 32); youth with early symptoms of distress (Stage 1a, n = 41); youth with subthreshold psychotic symptoms (Stage 1b, n = 72); and healthy comparison participants with no family history of serious mental illness (n = 37). Analyses included between-group comparisons of brain measurements and correlational analyses that aimed to identify significant associations between neuroimaging and clinical measurements. A machine-learning technique examined the discriminative properties of the clinical staging model. RESULTS: Subfield-specific limbic volume deficits were detected at every stage of risk for mental illness. A machine-learning classifier identified volume deficits within the body of the hippocampus, left amygdala nuclei, and medial-lateral nuclei of the thalamus that were most informative in differentiating between risk stages. CONCLUSION: Aberrant subfield-specific changes within the limbic system may serve as biological evidence to support transdiagnostic clinical staging in mental illness. Differential patterns of volume deficits characterize those at risk for mental illness and may be indicative of a risk-stage progression.

Testing a deep convolutional neural network for automated hippocampus segmentation in a longitudinal sample of healthy participants.

Subtle changes in hippocampal volumes may occur during both physiological and pathophysiological processes in the human brain. Assessing hippocampal volumes manually is a time-consuming procedure, however, creating a need for automated segmentation methods that are both fast and reliable over time. Segmentation algorithms that employ deep convolutional neural networks (CNN) have emerged as a promising solution for large longitudinal neuroimaging studies. However, for these novel algorithms to be useful in clinical studies, the accuracy and reproducibility should be established on independent datasets. Here, we evaluate the performance of a CNN-based hippocampal segmentation algorithm that was developed by Thyreau and colleagues - Hippodeep. We compared its segmentation outputs to manual segmentation and FreeSurfer 6.0 in a sample of 200 healthy participants scanned repeatedly at seven sites across Canada, as part of the Canadian Biomarker Integration Network in Depression consortium. The algorithm demonstrated high levels of stability and reproducibility of volumetric measures across all time points compared to the other two techniques. Although more rigorous testing in clinical populations is necessary, this approach holds promise as a viable option for tracking volumetric changes in longitudinal neuroimaging studies.

The Canadian Biomarker Integration Network in Depression (CAN-BIND): magnetic resonance imaging protocols

Studies of clinical populations that combine MRI data generated at multiple sites are increasingly common. The Canadian Biomarker Integration Network in Depression (CAN-BIND; www.canbind.ca) is a national depression research program that includes multimodal neuroimaging collected at several sites across Canada. The purpose of the current paper is to provide detailed information on the imaging protocols used in a number of CAN-BIND studies. The CAN-BIND program implemented a series of platform-specific MRI protocols, including a suite of prescribed structural and functional MRI sequences supported by real-time monitoring for adherence and quality control. The imaging data are retained in an established informatics and databasing platform. Approximately 1300 participants are being recruited, including almost 1000 with depression. These include participants treated with antidepressant medications, transcranial magnetic stimulation, cognitive behavioural therapy and cognitive remediation therapy. Our ability to analyze the large number of imaging variables available may be limited by the sample size of the substudies. The CAN-BIND program includes a multimodal imaging database supported by extensive clinical, demographic, neuropsychological and biological data from people with major depression. It is a resource for Canadian investigators who are interested in understanding whether aspects of neuroimaging ­ alone or in combination with other variables ­ can predict the outcomes of various treatment modalities.

Treatment History of Youth At-Risk for Serious Mental Illness.

OBJECTIVE: The aim was to describe treatment history including medications, psychosocial therapy and hospital visits of participants in the Canadian Psychiatric Risk and Outcomes Study (PROCAN). METHODS: PROCAN is a 2-site study of 243 youth/young adults aged 12 to 25 y, categorized into 4 groups: healthy controls ( n = 42), stage 0 (non-help seeking, asymptomatic with risk mainly family history of serious mental illness (SMI); n = 41), stage 1a (distress disorders; n = 52) and stage 1b (attenuated syndromes; n = 108). Participants were interviewed regarding lifetime and current treatments, including medications, psychosocial therapies and hospital visits. RESULTS: The number receiving baseline medications differed significantly across groups ( P < 0.001): 0% healthy controls, 14.6% stage 0, 32.7% stage 1a and 34.3% stage 1b. Further, 26.9% and 49.1% of stage 1a and stage 1b participants received psychosocial therapy at baseline, indicative of statistically significant differences among the groups ( P < 0.001). Similar results were observed for lifetime treatment history; stage 1b participants had the highest frequency of lifetime treatment. Medications started in adulthood (>18 y of age) were the most common for initiation of treatment compared to childhood (0 to 12 y) and adolescence (13 to 17 y) for stage 1a and 1b participants. Lifetime mental health hospital visits differed significantly across groups ( P < 0.001) and were most common in stage 1b participants (29.6%) followed by stage 1a (13.5%), stage 0 (4.9%) and healthy controls (2.4%). CONCLUSION: We found that treatment history for participants in the PROCAN study differed among the at-risk groups. Future initiatives focused on determining the effects of treatment history on SMI are warranted.

Modular Development of Cortical Gray Matter Across Childhood and Adolescence.

Brain maturation across childhood and adolescence is characterized by cortical thickness (CT) and volume contraction, and early expansion of surface area (SA). These processes occur asynchronously across the cortical surface, with functional, topographic, and network-based organizing principles proposed to account for developmental patterns. Characterizing regions undergoing synchronized development can help determine whether "maturational networks" overlap with well-described functional networks, and whether they are targeted by neurodevelopmental and psychiatric disorders. In the present study, we modeled changes with age in CT, SA, and volume from 335 typically developing subjects in the NIH MRI study of normal brain development, with 262 followed longitudinally for a total of 724 scans. Vertices showing similar maturation between 5 and 22 years were grouped together using data-driven clustering. Patterns of CT development distinguished sensory and motor regions from association regions, and were vastly different from SA patterns, which separated anterior from posterior regions. Developmental modules showed little similarity to networks derived from resting-state functional connectivity. Our findings present a novel perspective on maturational changes across the cortex, showing that several proposed organizing principles of cortical development co-exist, albeit in different structural parameters, and enable visualization of developmental trends occurring in parallel at remote cortical sites.