Faculty Bibliography

Learning, memory, and emotional regulation are all modulated by sleep. Sleep influences on neural circuit function and plasticity occur in all mammalian brain regions examined to date, including the noncanonical olfactory system, suggesting sleep disruption could have wide-ranging consequences on behavior and cognition. New evidence suggests that sleep disturbances during early development can have particularly insidious and long-lasting consequences. In particular, work from our lab and others suggests that early-life adverse events can disrupt sleep across the life span, thus contributing to a variety of negative cognitive and behavioral outcomes. These findings raise the possibility that interventions targeting sleep may have therapeutic value for children or adults exposed to early-life adverse events. Here, we describe sleep and sleep ontogeny and then describe the role of sleep in normal and pathological brain function. Finally, we explore how early-life adverse events and sleep disturbances may reciprocally interact to produce a range of psychopathological outcomes.
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Purpose/UNASSIGNED:Methylphenidate (MPH), the first-line medication in children with attention-deficit/hyperactivity disorder (ADHD), is associated with increased risk of sleep disorders. Melatonin has both hypnotic and chronobiotic properties that influence circadian rhythm sleep disorders. This study explores the effectiveness of melatonin in children with ADHD who developed sleep problems after starting MPH. Patients and methods/UNASSIGNED:This study, based on a clinical database, included 74 children (69 males, mean age 11.6±2.2 years) naturalistically treated with MPH (mean dosage 33.5±13.5 mg/d). The severity of sleep disorder (sleep onset delay) was recorded at baseline and after a follow-up of at least 4 weeks using a seven-point Likert scale according to the Clinical Global Impression Severity score. Effectiveness of melatonin on sleep (mean dosage 1.85±0.84 mg/d) after 4 weeks was assessed using a seven-point Likert scale according to the Clinical Global Impression Improvement (CGI-I) score, and patients who scored 1 (very much improved) or 2 (much improved) were considered responders. Results/UNASSIGNED:<0.001). According to the CGI-I score, 45 patients (60.8%) responded to the treatment with melatonin. Gender and age (children younger and older than 12 years) did not affect the response to melatonin on sleep. Patients with or without comorbidities did not differ according to sleep response. Specific comorbidities with disruptive behavior disorders (oppositional defiant disorder or conduct disorder), affective (mood and anxiety) disorders and learning disabilities did not affect the efficacy of melatonin on sleep. Treatment was well tolerated, and no side effects related to melatonin were reported. Conclusion/UNASSIGNED:In children with ADHD with sleep problems after receiving MPH treatment, melatonin may be an effective and safe treatment, irrespective of gender, age and comorbidities.

Unwanted sexual incidents on university campuses pose significant public health and safety risks for students. This study explored survivors' perspectives on secondary prevention of campus sexual assault and effective strategies for intervention programs for unwanted sexual incidents in university settings. Twenty-seven student survivors of unwanted sexual experiences participated in semi-structured in-depth interviews. Data were analyzed using thematic analysis and a constructionist perspective. The findings were contextualized using the ecological model. Barriers to reporting included concerns about one's story not being believed, personal minimization of the incident, belief that no action will be taken after reporting, confidentiality concerns, and other perceived costs of reporting. Survivors provided valuable insight on potentially effective prevention and intervention strategies to address the problem of unwanted sexual incidents on university campuses. These findings may be useful for prevention and intervention policies and programs in university settings and for providers who assist survivors of unwanted sexual experiences.

Early life maltreatment by the caregiver constitutes a major risk factor for the development of later-life psychopathologies, including fear-related pathologies. Here, we used an animal model of early life maltreatment induced by the Scarcity-Adversity Model of low bedding (LB) where the mother is given insufficient bedding for nest building while rat pups were postnatal days (PN) 8-12. To assess effects of maltreatment on the expression of threat-elicited defensive behaviors, animals underwent odor-shock threat conditioning at three developmental stages: late infancy (PN18), adolescence (PN45) or adulthood (>PN75) and tested the next day with odor only presentations (cue test). Results showed that in typically developing rats, the response to threat increases with maturation, although experience with maltreatment in early infancy produced enhanced responding to threat in infancy and adulthood, but a decrease in maltreated adolescents. To better understand the unique features of this decreased threat responding in adolescence, c-Fos expression was assessed within the amygdala and ventromedial prefrontal cortex (vmPFC) associated with the cued expression of threat learning. Fos counts across amygdala subregions were lower in LB rats compared to controls, while enhanced c-Fos expression was observed in the vmPFC prelimbic cortex (PL). Correlational analysis between freezing behavior and Fos revealed freezing levels were correlated with CeA in controls, although more global correlations were detected in LB-reared rats, including the BA, LA, and CeA. Functional connectivity analysis between brain regions showed that LB reared rats exhibited more diffuse interconnectivity across amygdala subnuclei, compared the more heterogeneous patterns observed in controls. In addition, functional connectivity between the IL and LA switched from positive to negative in abused adolescents. Overall, these results suggest that in adolescence, the unique developmental decrease in fear expression following trauma is associated with distinct changes in regional function and long-range connectivity, reminiscent of pathological brain function. These results suggest that early life maltreatment from the caregiver perturbs the developmental trajectory of threat-elicited behavior. Indeed, it is possible that this form of trauma, where the infant's safety signal or "safe haven" (the caregiver) is actually the source of the threat, produces distinct outcomes across development.

Understanding of early brain changes has the potential to investigate imaging biomarkers for pre-symptomatic diagnosis and thus opportunity for optimal therapeutic intervention, for example in early diagnosis of infants at risk to autism or altered development of infants to drug exposure. In this paper, we propose a framework to analyze longitudinal changes of structural connectivity in the early developing infant brain by exploring underlying network components of brain structural connectivity and its changes with age. Structural connectivity is a non-negative sparse network. Projective non-negative matrix factorization (PNMF) offers benefits in sparsity and learning fewer parameters for non-negative sparse data. The number of matrix subcomponents was estimated by automatic relevance determination PNMF (ARDPNMF) for brain connectivity networks for the given data. We apply linear mixed effect modeling on the resulting loadings from ARDPNMF to model longitudinal network component changes over time. The proposed framework was validated on a synthetic example generated by known linear mixed effects on loadings of the known number of bases with different levels of additive noises. Feasibility of the framework on real data has been demonstrated by analysis of structural connectivity networks of high angular resonance diffusion imaging (HARDI) data from an ongoing neuroimaging study of autism. A total of 139 image data sets from high-risk and low-risk subjects acquired at multiple time points have been processed. Results demonstrate the feasibility of the framework to analyze connectivity network properties as a function of age and the potential to eventually explore differences associated with risk status

Academic medical centers (AMCs) today prioritize digital innovation. In efforts to develop and disseminate the best technology for their institutions, challenges arise in organizational structure, cross-disciplinary collaboration, and creative and agile problem solving that are essential for successful implementation. To address these challenges, the Digital DesignLab was created at NYU Langone Health to provide structured processes for assessing and supporting the capacity for innovative digital development in our research and clinical community. Digital DesignLab is an enterprise level, multidisciplinary, digital development team that guides faculty and student innovators through a digital development "pipeline", which consists of intake, discovery, bootcamp, development. It also provides a framework for digital health innovation and dissemination at the institution. This paper describes the Digital DesignLab's creation and processes, and highlights key lessons learned to support digital health innovation at AMCs.