Faculty Bibliography

A common coordinate space enabling comparison across individuals is vital to understanding human brain organization and individual differences. By leveraging dimensionality reduction algorithms, high-dimensional fMRI data can be represented in a low-dimensional space to characterize individual features. Such a representative space encodes the functional architecture of individuals and enables the observation of functional changes across time. However, determining comparable functional features across individuals in resting-state fMRI in a way that simultaneously preserves individual-specific connectivity structure can be challenging. In this work we propose scalable joint embedding to simultaneously embed multiple individual brain connectomes within a common space that allows individual representations across datasets to be aligned. Using Human Connectome Project data, we evaluated the joint embedding approach by comparing it to the previously established orthonormal alignment model. Alignment using joint embedding substantially increased the similarity of functional representations across individuals while simultaneously capturing their distinct profiles, allowing individuals to be more discriminable from each other. Additionally, we demonstrated that the common space established using resting-state fMRI provides a better overlap of task-activation across participants. Finally, in a more challenging scenario - alignment across a lifespan cohort aged from 6 to 85 - joint embedding provided a better prediction of age (r2 = 0.65) than the prior alignment model. It facilitated the characterization of functional trajectories across lifespan. Overall, these analyses establish that joint embedding can simultaneously capture individual neural representations in a common connectivity space aligning functional data across participants and populations and preserve individual specificity.

The occurrence of dreaming during rapid eye movement (REM) sleep prompts interest in the role of REM sleep in hippocampal-dependent episodic memory. Within the mammalian hippocampus, the dentate gyrus (DG) has the unique characteristic of exhibiting neurogenesis persisting into adulthood. Despite their small numbers and sparse activity, adult-born neurons (ABNs) in the DG play critical roles in memory; however, their memory function during sleep is unknown. Here, we investigate whether young ABN activity contributes to memory consolidation during sleep using Ca²⁺ imaging in freely moving mice. We found that contextual fear learning recruits a population of young ABNs that are reactivated during subsequent REM sleep against a backdrop of overall reduced ABN activity. Optogenetic silencing of this sparse ABN activity during REM sleep alters the structural remodeling of spines on ABN dendrites and impairs memory consolidation. These findings provide a causal link between ABN activity during REM sleep and memory consolidation.

Importance/UNASSIGNED:The Modular Approach to Therapy for Children (MATCH) was developed to address the comorbidities common among clinically referred youth, with beneficial outcomes shown in 2 US randomized clinical trials, where it outperformed both usual clinical care and single disorder-specific treatments. Objective/UNASSIGNED:To determine whether MATCH training of clinicians would result in more use of empirically supported treatment (EST) and better clinical outcomes than usual care (UC) in the publicly funded, multidisciplinary context of New Zealand. Design, Setting, and Participants/UNASSIGNED:This multisite, single-blind, computer-randomized clinical effectiveness trial compared MATCH with UC in child and adolescent mental health services in 5 regions of New Zealand. Recruitment occurred from March 2014 to July 2015, and a 3-month follow-up assessment was completed by May 2016. Clinicians at participating child and adolescent mental health services were randomized (1:1) to undertake training in MATCH or to deliver UC, and young people with anxiety, depression, trauma-related symptoms, or disruptive behavior seeking treatment at child and adolescent mental health services were randomized (1:1) to receive MATCH or UC. Participants and research assistants were blind to allocation. Data analysis was performed from April 2016 to July 2017. Interventions/UNASSIGNED:MATCH comprises EST components for flexible management of common mental health problems. UC includes case management and psychological therapies. Both can include pharmacotherapy. Main Outcomes and Measures/UNASSIGNED:There were 3 primary outcomes: trajectory of change of clinical severity, as measured by weekly ratings on the Brief Problem Monitor (BPM); fidelity to EST content, as measured by audio recordings of therapy sessions coded using the Therapy Integrity in Evidence Based Interventions: Observational Coding System; and efficiency of service delivery, as measured by duration of therapy (days) and clinician time (minutes). Results/UNASSIGNED:The study included 65 clinicians (mean age, 38.7 years; range, 23.0-64.0 years; 54 female [83%]; MATCH, 32 clinicians; UC, 33 clinicians) and 206 young people (mean age, 11.2 years; range 7.0-14.0 years; 122 female [61%]; MATCH, 102 patients; UC, 104 patients). For the BPM total ratings for parents, there was a mean (SE) slope of -1.04 (0.14) (1-year change, -6.12) in the MATCH group vs -1.04 (0.10) (1-year change, -6.17) in the UC group (effect size, 0.00; 95% CI, -0.27 to 0.28; P = .96). For the BPM total for youths, the mean (SE) slope was -0.74 (0.15) (1-year change, -4.35) in the MATCH group vs -0.73 (0.10) (1-year change, -4.32) in the UC group (effect size, -0.02; 95% CI, -0.30 to 0.26; P = .97). Primary analyses (intention-to-treat) showed no difference in clinical outcomes or efficiency despite significantly higher fidelity to EST content in the MATCH group (58 coded sessions; mean [SD], 80.0% [20.0%]) than the UC group (51 coded sessions; mean [SD], 57.0% [32.0%]; F(1,108) = 23.0; P < .001). With regard to efficiency of service delivery, there were no differences in total face-to-face clinician time between the MATCH group (mean [SD], 806 [527] minutes) and the UC group (mean [SD], 677 [539] minutes) or the overall duration of therapy between the MATCH group (mean [SD], 167 [107 days]) and the UC group (mean [SD], 159 [107] days). Conclusions and Relevance/UNASSIGNED:MATCH significantly increased adherence to EST practices but did not improve outcomes or efficiency. The nonsuperiority of MATCH may be attributable to high levels of EST use in UC in New Zealand. Trial Registration/UNASSIGNED:Australian New Zealand Clinical Trials Registry Identifier: ACTRN12614000297628.

OBJECTIVE:To estimate long-term stimulant treatment associations on standardized height, weight and BMI trajectories from childhood to adulthood in the Multimodal Treatment Study of Attention-Deficit/Hyperactivity Disorder (MTA). METHOD/METHODS:Of 579 children with DSM-IV ADHD-Combined Type at baseline (ages 7.0-9.9 years) and 289 classmates (local normative comparison group, LNCG), 568 and 258 respectively, were assessed 8 times over 16 years (final mean age = 24.7). Parent interview data established subgroups with self-selected Consistent (N=53, 9%), Inconsistent (N=374, 66%), and Negligible (N=141, 25%) stimulant medication use, as well as cases starting stimulants prior to MTA entry (N=211, 39%). Height and weight growth trajectories were calculated for each subgroup. RESULTS:Height z-scores trajectories differed among subgroups (F=2.22, P<0.0001) and by stimulant use prior to study entry (F=2.22, P<0.001). The subgroup x assessment interaction was significant (F=2.81, P<0.0001). Paired comparisons revealed significant subgroup differences at end-point: Consistent shorter than Negligible (-0.66 z-units / -4.06 cm /1.6 inches, t=-3.17, P<0.0016), Consistent shorter than Inconsistent (-0.45 z-units / -2.74 cm / -1.08 inches, t=-2.39, P<0.0172), and the Consistent shorter than LNCG (-0.54 z-units/+3.34 cm/ 1.31 inches, t=-3.30, P<0.001). Weight z-scores initially diverged among subgroups, converged in adolescence, and then diverged again in adulthood when the Consistent outweighed the LNCG (+ 3.561 z-units / +7.47 kg / +16.46 pounds, P<0.0001). CONCLUSION/CONCLUSIONS:Compared with those negligibly medicated and the LNCG, 16 years of consistent stimulant treatment of children with ADHD in the MTA was associated with changes in height trajectory, a reduction of adult height, and an increase in weight and BMI.

BACKGROUND:The identification of an early and objective marker of language impairment in autism spectrum disorder (ASD) has the potential to lead to earlier language intervention for affected children. The mismatch negativity (MMN), a passive auditory evoked potential, offers insight into the brain's ability to direct attention to novel sounds. Since exposure to speech is necessary for learning to map meaning onto phonemes, we predicted slower MMN responses to speech sounds would indicate presence of language impairment in ASD. METHODS:We explored the relationship between MMN latency in children ages 5-10 with ASD plus language impairment (ASD + LI), ASD minus language impairment (ASD-LI), and typically developing children (TD) during an auditory oddball experiment presenting speech and pure tone sounds. RESULTS:Contrary to our prediction, children with ASD + LI demonstrated decreased MMN latency in the left hemisphere in response to novel vowel sounds compared to children with ASD-LI and TD controls. Parent responses to the Sensory Experiences Questionnaire revealed that all participating individuals with ASD were hypersensitive to sounds. CONCLUSIONS:Our results lend support to the theory that some children with ASD + LI have increased connectivity in primary sensory cortices at the expense of connectivity to association areas of the brain. This may account for faster speech sound processing despite low language scores in these children. Future studies should focus on individuals with language impairment and hyper-or hyposensitivity to sounds.

This article describes the application of the Collective Impact Model as an innovative conceptual framework for developing a pedagogical process for advancing academic success and retention for underrepresented nursing students. A more diverse nursing workforce is critical to promoting health equity and supporting a culture of health by providing access to culturally and linguistically appropriate care. By strategically applying this framework to a complex issue in nursing education, we discuss a process that may lead to increased academic success and NCLEX®RN pass rates for underrepresented students.

Early behaviors that differentiate later biomarkers for psychopathology can guide preventive efforts while also facilitating pathophysiological research. We tested whether error-related negativity (ERN) moderates the link between early behavior and later psychopathology in two early childhood phenotypes: behavioral inhibition and irritability. From ages 2 to 7 years, children (n = 291) were assessed longitudinally for behavioral inhibition (BI) and irritability. Behavioral inhibition was assessed via maternal report and behavioral responses to novelty. Childhood irritability was assessed using the Child Behavior Checklist. At age 12, an electroencephalogram (EEG) was recorded while children performed a flanker task to measure ERN, a neural indicator of error monitoring. Clinical assessments of anxiety and irritability were conducted using questionnaires (i.e., Screen for Child Anxiety Related Disorders and Affective Reactivity Index) and clinical interviews. Error monitoring interacted with early BI and early irritability to predict later psychopathology. Among children with high BI, an enhanced ERN predicted greater social anxiety at age 12. In contrast, children with high childhood irritability and blunted ERN predicted greater irritability at age 12. This converges with previous work and provides novel insight into the specificity of pathways associated with psychopathology.