Faculty Bibliography

The essence of who we are depends on our brains. They enable us to think, to feel joy and sorrow, communicate through speech, reflect on the moments of our lives, and to anticipate, plan for, and worry about our imagined futures. Although some of our abilities are comparatively new, key features of our behavior have deep roots that can be traced to the beginning of life. By following the story of behavior, step-by-step, over its roughly four-billion-year trajectory, we come to understand both how similar we are to all organisms that have ever lived, and how different we are from even our closest animal relatives. We care about our differences because they are ours. But differences do not make us superior; they simply make us different.

Children with DBDs experience increased academic and social challenges. The MFG service delivery model, for families of youth with DBDs, was developed. This current study seeks to examine how the presence of ADHD moderates the outcomes for families who go through the MFG intervention. This analysis included families who were enrolled in the MFG intervention. Children were grouped by ADHD severity to examine how symptom severity moderates various behavioral outcomes. Results showed that several outcomes were moderated by ADHD severity. These results indicate that ADHD severity can have an impact on certain treatment outcomes, both positively and negatively.

The locus coeruleus (LC) is the primary source of noradrenergic projections to the forebrain, and, in prefrontal cortex, is implicated in decision-making and executive function. LC neurons phase-lock to cortical infra-slow wave oscillations during sleep. Such infra-slow rhythms are rarely reported in awake states, despite their interest, since they correspond to the time scale of behavior. Thus, we investigated LC neuronal synchrony with infra-slow rhythms in awake rats performing an attentional set-shifting task. Local field potential (LFP) oscillation cycles in prefrontal cortex and hippocampus on the order of 0.4 Hz phase-locked to task events at crucial maze locations. Indeed, successive cycles of the infra-slow rhythms showed different wavelengths, as if they are periodic oscillations that can reset phase relative to salient events. Simultaneously recorded infra-slow rhythms in prefrontal cortex and hippocampus could show different cycle durations as well, suggesting independent control. Most LC neurons (including optogenetically identified noradrenergic neurons) recorded here were phase-locked to these infra-slow rhythms, as were hippocampal and prefrontal units recorded on the LFP probes. The infra-slow oscillations also phase-modulated gamma amplitude, linking these rhythms at the time scale of behavior to those coordinating neuronal synchrony. This would provide a potential mechanism where noradrenaline, released by LC neurons in concert with the infra-slow rhythm, would facilitate synchronization or reset of these brain networks, underlying behavioral adaptation.

Evidence-based interventions (EBIs) are considered the gold standard but it is unclear if they are effective across settings. Reach Out and Stay Strong, Essentials for new Mothers (ROSE) has been shown to prevent postpartum depression in clinical settings, but has not been implemented or tested in homeless populations. We used the Exploration, Preparation, Implementation and Sustainment (EPIS) model overlaid with the Dynamic Adaptation Process (DAP) to adapt ROSE for implementation in a homeless shelter system in a large U.S. city, using feedback from both the organization and community. The adapted intervention was called Strong in Shelter (SIS). In this paper, we present 4 DAPS (April, 2018- December, 2020); the EPIS stages within each DAP are described. The Exploration Stage is centered around early and ongoing engagement with shelter providers and residents. The Preparation Stage includes adaptations based on learnings from the Exploration and the Implementation Stages from previous DAPs. The Implementation Stage highlights what we learned from implementation and both quantitative and qualitative feedback from shelter staff and residents. Following the DAP cycles, we created scalable plans in the Sustainment Stage. Thematic analysis was used to identify, analyze and report patterns within qualitative data, and descriptive analyses were conducted with quantitative data. Participant engagement and satisfaction were high and facilitators reported implementing SIS with fidelity to ROSE"™s core components. By engaging staff and the participants early and continually, and utilizing an iterative and flexible adaptation process, EBIs such as ROSE can be adapted and implemented with fidelity in new settings.

This paper develops a Bayesian model with a flexible link function connecting a binary treatment response to a linear combination of covariates and a treatment indicator and the interaction between the two. Generalized linear models allowing data-driven link functions are often called "single-index models" and are among popular semi-parametric modeling methods. In this paper, we focus on modeling heterogeneous treatment effects, with the goal of developing a treatment benefit index (TBI) incorporating prior information from historical data. The model makes inference on a composite moderator of treatment effects, summarizing the effect of the predictors within a single variable through a linear projection of the predictors. This treatment benefit index can be useful for stratifying patients according to their predicted treatment benefit levels and can be especially useful for precision health applications. The proposed method is applied to a COVID-19 treatment study.

Introduction: Transitions between sleep and waking and sleep-dependent cortical oscillations are heavily dependent on GABAergic neurons. Importantly, GABAergic neurons are especially sensitive to developmental ethanol exposure, suggesting a potential unique vulnerability of sleep circuits to early ethanol. In fact, developmental ethanol exposure can produce long-lasting impairments in sleep, including increased sleep fragmentation and decreased delta wave amplitude. Here, we assessed the efficacy of optogenetic manipulations of somatostatin (SST) GABAergic neurons in the neocortex of adult mice exposed to saline or ethanol on P7, to modulate cortical slow-wave physiology. Methods: SST-cre × Ai32 mice, which selectively express channel rhodopsin in SST neurons, were exposed to ethanol or saline on P7. This line expressed similar developmental ethanol induced loss of SST cortical neurons and sleep impairments as C57BL/6By mice. As adults, optical fibers were implanted targeting the prefrontal cortex (PFC) and telemetry electrodes were implanted in the neocortex to monitor slow-wave activity and sleep-wake states. Results: Optical stimulation of PFC SST neurons evoked slow-wave potentials and long-latency single-unit excitation in saline treated mice but not in ethanol mice. Closed-loop optogenetic stimulation of PFC SST neuron activation on spontaneous slow-waves enhanced cortical delta oscillations, and this manipulation was more effective in saline mice than P7 ethanol mice. Discussion: Together, these results suggest that SST cortical neurons may contribute to slow-wave impairment after developmental ethanol.

Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by a repeat expansion mutation in the promotor region of the FMR1 gene resulting in transcriptional silencing and loss of function of fragile X messenger ribonucleoprotein 1 protein (FMRP). FMRP has a well-defined role in the early development of the brain. Thus, loss of the FMRP has well-known consequences for normal cellular and synaptic development leading to a variety of neuropsychiatric disorders including an increased prevalence of amygdala-based disorders. Despite our detailed understanding of the pathophysiology of FXS, the precise cellular and circuit-level underpinnings of amygdala-based disorders is incompletely understood. In this review, we discuss the development of the amygdala, the role of neuromodulation in the critical period plasticity, and recent advances in our understanding of how synaptic and circuit-level changes in the basolateral amygdala contribute to the behavioral manifestations seen in FXS.

There is, in the content of the Journal, an embarrassment of riches, and picking a "best" seems to demand a certain qualification: is the "best" the most interesting, most surprising, most educational, most important, most provocative, most enjoyable? How to choose? We are hardly unbiased and can admit to a special affection for the ones that we and the authors worked hardest on, hammering version after version into shape. Acknowledging these biases, here are the 2022 articles that we think deserve your attention or at least a second read.