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Adults with psychotic disorders have dysconnectivity in critical brain networks, including the default mode (DM) and the cingulo-opercular (CO) networks. However, it is unknown whether such deficits are present in youth with less severe symptoms. We conducted a multivariate connectome-wide association study examining dysconnectivity with resting state functional magnetic resonance imaging in a population-based cohort of 188 youths aged 8-22 years with psychosis-spectrum (PS) symptoms and 204 typically developing (TD) comparators. We found evidence for multi-focal dysconnectivity in PS youths, implicating the bilateral anterior cingulate, frontal pole, medial temporal lobe, opercular cortex and right orbitofrontal cortex. Follow-up seed-based and network-level analyses demonstrated that these results were driven by hyper-connectivity among DM regions and diminished connectivity among CO regions, as well as diminished coupling between frontal and DM regions. Collectively, these results provide novel evidence for functional dysconnectivity in PS youths, which show marked correspondence to abnormalities reported in adults with established psychotic disorders.

Arterial spin labeling (ASL) based cerebral blood flow (CBF) imaging complements blood oxygenation level dependent (BOLD) imaging with a measure that is more quantitative and has better specificity to neuronal activation. Relative to gradient echo (GE) BOLD, spin echo (SE) BOLD has better spatial specificity because it is less biased to large draining veins. While there have been many studies comparing simultaneously acquired CBF data with GE BOLD data in fMRI, there have been few studies comparing CBF with SE BOLD and no study comparing all three. We present a pulse sequence that simultaneously acquires CBF data with a separate labeling coil, GE BOLD and SE BOLD images. Simultaneous acquisition avoids inter-scan variability, allowing more direct assessment and comparison of each contrast’s relative specificity and reproducibility. Furthermore, it facilitates studies that may benefit from multiple complementary measures.

Highlights • Children with or without ADHD have moderate/high R-fMRI test–retest reliability. • Reliability is greater in controls than ADHD across most R-fMRI metrics. • Regional differences in ICC related to diagnostic groups reflect underlying pathophysiology for ADHD affecting both inter and intra subject variability., To date, only one study has examined test–retest reliability of resting state fMRI (R-fMRI) in children, none in clinical developing groups. Here, we assessed short-term test–retest reliability in a sample of 46 children (11–17.9 years) with attention-deficit/hyperactivity disorder (ADHD) and 57 typically developing children (TDC). Our primary test–retest reliability measure was the intraclass correlation coefficient (ICC), quantified for a range of R-fMRI metrics. We aimed to (1) survey reliability within and across diagnostic groups, and (2) compare voxel-wise ICC between groups. We found moderate-to-high ICC across all children and within groups, with higher-order functional networks showing greater ICC. Nearly all R-fMRI metrics exhibited significantly higher ICC in TDC than in children with ADHD for one or more regions. In particular, posterior cingulate and ventral precuneus exhibited group differences in ICC across multiple measures. In the context of overall moderate-to-high test–retest reliability in children, regional differences in ICC related to diagnostic groups likely reflect the underlying pathophysiology for ADHD. Our currently limited understanding of the factors contributing to inter- and intra-subject variability in ADHD underscores the need for large initiatives aimed at examining their impact on test–retest reliability in both clinical and developing populations.

Arterial spin labeling-based cerebral blood flow imaging complements blood oxygenation level dependent (BOLD) imaging with a measure that is more quantitative and has better specificity to neuronal activation. Relative to gradient echo BOLD, spin echo BOLD has better spatial specificity because it is less biased to large draining veins. Although there have been many studies comparing simultaneously acquired cerebral blood flow data with gradient echo BOLD data in fMRI, there have been few studies comparing cerebral blood flow with SE BOLD and no study comparing all three. We present a pulse sequence that simultaneously acquires cerebral blood flow data with a separate labeling coil, gradient echo BOLD, and spin echo BOLD images. Simultaneous acquisition avoids interscan variability, allowing more direct assessment and comparison of each contrast's relative specificity and reproducibility. Furthermore, it facilitates studies that may benefit from multiple complementary measures.