Faculty Bibliography

New large neuroimaging studies, such as the Adolescent Brain Cognitive Development study (ABCD) and Human Connectome Project (HCP) Development studies are adopting a new T1-weighted imaging sequence with prospective motion correction (PMC) in favor of the more traditional 3-Dimensional Magnetization-Prepared Rapid Gradient-Echo Imaging (MPRAGE) sequence. Here, we used a developmental dataset (ages 5-21, N = 348) from the Healthy Brain Network (HBN) Initiative to directly compare two widely used MRI structural sequences: one based on the Human Connectome Project (MPRAGE) and another based on the ABCD study (MPRAGE+PMC). We aimed to determine if the morphometric measurements obtained from both protocols are equivalent or if one sequence has a clear advantage over the other. The sequences were also compared through quality control measurements. Inter- and intra-sequence reliability were assessed with another set of participants (N = 71) from HBN that performed two MPRAGE and two MPRAGE+PMC sequences within the same imaging session, with one MPRAGE (MPRAGE1) and MPRAGE+PMC (MPRAGE+PMC1) pair at the beginning of the session and another pair (MPRAGE2 and MPRAGE+PMC2) at the end of the session. Intraclass correlation coefficients (ICC) scores for morphometric measurements such as volume and cortical thickness showed that intra-sequence reliability is the highest with the two MPRAGE+PMC sequences and lowest with the two MPRAGE sequences. Regarding inter-sequence reliability, ICC scores were higher for the MPRAGE1 - MPRAGE+PMC1 pair at the beginning of the session than the MPRAGE1 - MPRAGE2 pair, possibly due to the higher motion artifacts in the MPRAGE2 run. Results also indicated that the MPRAGE+PMC sequence is robust, but not impervious, to high head motion. For quality control metrics, the traditional MPRAGE yielded better results than MPRAGE+PMC in 5 of the 8 measurements. In conclusion, morphometric measurements evaluated here showed high inter-sequence reliability between the MPRAGE and MPRAGE+PMC sequences, especially in images with low head motion. We suggest that studies targeting hyperkinetic populations use the MPRAGE+PMC sequence, given its robustness to head motion and higher reliability scores. However, neuroimaging researchers studying non-hyperkinetic participants can choose either MPRAGE or MPRAGE+PMC sequences, but should carefully consider the apparent tradeoff between relatively increased reliability, but reduced quality control metrics when using the MPRAGE+PMC sequence.

BACKGROUND:The treatment of suicidal patients often suffers owing to a lack of integrated care and standardized approaches for identifying and reducing risk. The National Strategy for Suicide Prevention endorsed the Zero Suicide (ZS) model, a multi-component, system-wide approach to identify, engage, and treat suicidal patients. The ZS model is a framework for suicide prevention in healthcare systems with the aspirational goal of eliminating suicide in healthcare. While the approach is widely endorsed, it has yet to be evaluated in a systematic manner. This trial evaluates two ZS implementation strategies statewide in specialty mental health clinics. METHODS/STUDY DESIGN/UNASSIGNED:This trial is the first large-scale implementation of the ZS model in mental health clinics using the Assess, Intervene, and Monitor for Suicide Prevention (A-I-M) clinical model. Using a hybrid effectiveness-implementation type 1 design, we are testing the effectiveness of ZS implementation in 186 mental health clinics in 95 agencies in New York State. Agencies are randomly assigned to either: "Basic Implementation" (BI; a large group didactic learning collaboratives) or "Enhanced Implementation" (EI; participatory small group learning collaboratives; enhanced consultation for site champions). Primary outcomes include suicidal behaviors, hospitalizations and Emergency Department visits; implementation outcomes include protocol adoption, protocol fidelity and barriers/facilitators to implementation. DISCUSSION/CONCLUSIONS:This project has the potential to have a significant public health impact by determining the effectiveness of the ZS model in mental health clinics, a setting where suicide attempts and suicides occur at a higher rate than any other healthcare setting. It will also provide guidance on the implementation level required to achieve uptake and sustainability of ZS. TRIAL REGISTRATION/BACKGROUND:N/A.

OBJECTIVE:Autoimmune encephalitis (AE) is a highly treatable neurologic condition that can cause psychosis. Screening for AE is not currently recommended in routine workup for first-episode psychosis (FEP), owing partly to the high cost of testing for AE-associated neuronal autoantibodies. METHODS:This study used a decision-analytic model to estimate the cost-effectiveness of routine serum screening for AE compared with clinically targeted screening in patients with FEP. Model parameters drawn from prior published literature included the prevalence of neuronal autoantibodies in FEP (4.5%), serum autoantibody panel cost (US $291), remission probability with antipsychotics (0.58), and remission probability with immunotherapy for patients diagnosed with AE (0.85). Outcomes included quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs), assessed over a 5-year horizon from the US health care sector and societal perspectives. ICER thresholds of $50,000/QALY to $150,000/QALY were used to define cost-effectiveness. The analysis was conducted between June 2018 and January 2020. RESULTS:Routine screening led to mean QALY gains of 0.008 among all patients and 0.174 among the subgroup of patients with neuronal autoantibodies. Mean costs increased by $780 from a societal perspective and $1,150 from a health care sector perspective, resulting in ICERs of $99,330/QALY and $147,460/QALY, respectively. Incorporating joint input data uncertainty, the likelihood routine screening has an ICER ≤ $150,000/QALY was 55% from a societal perspective and 37% from a health care sector perspective. The model parameter with the greatest contribution to overall uncertainty was the effectiveness of immunotherapy relative to antipsychotics. CONCLUSIONS:Routine screening for AE in patients with FEP may be cost-effective in the United States. As further immunotherapy effectiveness data become available, a more definitive recommendation to perform routine screening could be warranted.

INTRODUCTION/BACKGROUND:effect tends to disappear with increasing absolute age. Therefore, it is possible that young children erroneously diagnosed with ADHD due to their month of birth present a lower chance to have their diagnosis confirmed at a later age, artificially reinforcing the low persistence of ADHD across the lifespan. This protocol outlines an individual patient data (IPD) meta-analysis of prospective observational studies to explore the role of the month of birth in the low persistence of ADHD across the lifespan. METHODS AND ANALYSIS/UNASSIGNED:Five databases will be systematically searched in order to find prospective observational studies where the presence of ADHD is assessed both at baseline and at a follow-up of at least 4 years. We will use a two-stage IPD meta-analytic approach to estimate the role of the month of birth in the persistence of ADHD. Various sensitivity analyses will be performed to assess the robustness of the results. ETHICS AND DISSEMINATION/UNASSIGNED:No additional data will be collected and no de-identified raw data will be used. Ethics approval is thus not required for the present study. Results of this IPD meta-analysis will be submitted for publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER/UNASSIGNED:CRD42020212650.

Patterns of functional connectivity are unique at the individual level, enabling test-retest matching algorithms to identify a subject from among a group using only their functional connectome. Recent findings show that accuracies of these algorithms in children increase with age. Relatedly, the persistence of functional connectivity (FC) patterns across tasks and rest also increases with age. This study investigated the hypothesis that within-subject stability and between-subject similarity of the whole-brain pediatric connectome are developmentally relevant outcomes. Using data from 210 help-seeking children and adolescents, ages 6-21 years (Healthy Brain Network Biobank), we computed whole-brain FC matrices for each participant during two different movies (MovieDM and MovieTP) and two runs of task-free rest (all from a single scan session) and fed these matrices to a test-retest matching algorithm. We replicated the finding that matching accuracies for children and youth (ages 6-21 years) are low (18-44%), and that cross-state and cross-movie accuracies were the lowest. Results also showed that parcellation resolution and the number of volumes used in each matrix affect fingerprinting accuracies. Next, we calculated three measures of whole-connectome stability for each subject: cross-rest (Rest1-Rest2), cross-state (MovieDM-Rest1), and cross-movie (MovieDM-MovieTP), and three measures of within-state between-subject connectome similarity for Rest1, MovieDM, and MovieTP. We show that stability and similarity were correlated, but that these measures were not related to age. A principal component analysis of these measures yielded two components that we used to test for brain-behavior correlations with IQ, general psychopathology, and social skills measures (n = 119). The first component was significantly correlated with the social skills measure (r=-0.26, p = 0.005). Post hoc correlations showed that the social skills measure correlated with both cross-rest stability (r=-0.29, p = 0.001) and with connectome similarity during MovieDM (r=-0.28, p = 0.002). These findings suggest that the stability and similarity of the whole-brain connectome relate to the development of social skills. We infer that the maturation of the functional connectome simultaneously achieves patterns of FC that are distinct at the individual subject level, that are shared across individuals, and that are persistent across states and across runs-features which presumably combine to optimize neural processing during development. Future longitudinal work could reveal the developmental trajectories of stability and similarity of the connectome.

Early neural development and maternal health have critical long-term effects on children's mental health and outcomes later in life. As child mental disorders continue to rise nationwide, a number of states are considering new ways of investing in the critical early childhood period to prevent later poor outcomes and reduce the burden on the mental health system. Because most state mental health authorities (SMHAs) have no dedicated mental health dollars to devote to this early, crucial period of child development, building coalitions is key to implementing prevention and promotion programming. The authors describe two issues-coalition building and contractual considerations-that should be considered as SMHAs develop these types of policies or plan new prevention and promotion initiatives. Coalition building includes establishing the structural conditions for implementing a prevention or promotion initiative, resolving workforce issues (i.e., who will carry the program out), and engaging communities and families in the effort. Contractual considerations include establishing agreed-upon measures and metrics to monitor outcomes, assigning accountability for those outcomes, and delineating realistic time frames for these investments before expecting improved outcomes. The promise of moving services upstream to support early childhood development, to prevent mental health issues from derailing children's development, and to promote children's well-being are goals that are within reach.

Motor skills are important for development. Everything infants do involves motor skills - postural, locomotor, and manual actions; exploratory actions; social interactions; and actions with artifacts. Put another way, all behavior is motor behavior, and thus motor skill acquisition is synonymous with behavioral development. Age norms for basic motor skills provide useful diagnostics for "typical" development, but cultural differences in child-rearing practices influence skill onset ages. Whenever they emerge, motor skills lay the foundation for development by opening up new opportunities for learning. Postural control brings new parts of the environment into view and into reach; locomotion makes the larger world accessible; manual skills promote new forms of interactions with objects; and motor skills involving every part of the body enhance opportunities for social interaction. Thus, motor skills can instigate a cascade of developments in domains far afield from motor behavior - perception and cognition, language and communication, emotional expression and regulation, physical growth and health, and so on. Finally, motor skill acquisition makes behavior increasingly functional and flexible. Infants learn to tailor behavior to variations in their body and environment and to discover or construct new means to achieve their goals.

The precuneus (PreC; Brodmann area 7), a key hub within the default mode network (DMN) displays amyloid and tau-containing neurofibrillary tangle (NFT) pathology during the onset of Alzheimer's disease (AD). PreC layer III projection neurons contain lysosomal hydrolase cathepsin D (CatD), 14)a marker of neurons vulnerable to NFT pathology. Here we applied single population laser capture microdissection coupled with custom-designed microarray profiling to determine the genetic signature of PreC CatD-positive-layer III neurons accrued from postmortem tissue obtained from the Rush Religious Orders Study (RROS) cases with a premortem clinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment (MCI) and AD. Expression profiling revealed significant differential expression of key transcripts in MCI and AD compared to NCI that underlie signaling defects, including dysregulation of genes within the endosomal-lysosomal and autophagy pathways, cytoskeletal elements, AD-related genes, ionotropic and metabotropic glutamate receptors, cholinergic enzyme and receptors, markers of monoamine neurotransmission as well as steroid-related transcripts. Pervasive defects in both MCI and AD were found in select transcripts within these key gene ontology categories, underscoring the vulnerability of these corticocortical neurons during the onset and progression of dementia. Select PreC dysregulated genes detected via custom-designed microarray analysis were validated using qPCR. In summary, expression profiling of CatD positive PreC layer III neurons revealed significant dysregulation of a mosaic of genes in MCI and AD that were not previously appreciated in terms of their indication of systems-wide signaling defects in a key hub of the DMN. This article is protected by copyright. All rights reserved.