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NIMH - National Institute of Mental Health

Childhood anxiety and depression (collectively, internalizing disorders) are a critical public health need. Early adolescence and the emergence of puberty is a pivotal moment wherein internalizing symptoms begin to rise, especially in girls. It is also a period when subcortical brain systems subserving motivated behaviors, including amygdala (negative emotions) and dorsal/ventral striatum (reward processing) increase in reactivity, and regu- latory capacity in the frontoparietal network (FPN) decreases. These cognitive-affective networks are linked to development of internalizing disorders, but the specific mechanisms remain poorly understood. The proposed project will investigate two such constructs that are impacted by these developing cognitive-affective brain net- works, perseverative thought disengagement and reward learning, in order to characterize their relationship to internalizing symptoms and the role of puberty in early-adolescent girls. Perseverative thought (PT) disengage- ment refers to the capacity to disengage from intrusive, repetitive and uncontrollable thoughts such as worries and rumination (i.e., PT), which are known contributors to internalizing symptoms in girls. Reward learning refers to the skills and strategies used to learn from rewards in the environment, which requires solving the explore/ex- ploit dilemma (whether to explore for new rewards or exploit known rewards). Using computational modeling of explore/exploit paradigms, deficits in uncertainty-directed exploration, or exploration aimed specifically at un- known parts of the environment, is linked to internalizing symptoms. Using a parallel structure, the Aims of this project will be to characterize the neural correlates of 1) PT disengagement and 2) uncertainty-directed explora- tion and their relationship to internalizing symptoms in 100 adolescent girls aged 9-14. As an Exploratory Aim, we will investigate relationships between the two constructs in these same participants. This project will take a transdiagnostic approach, recruiting girls on the basis of self-reported PT, as a risk factor for future internalizing symptoms. Girls will complete two study visits: an interview (conducted virtually) to determine topics of frequent PT, and an MRI visit to complete both PT disengagement and reward learning tasks. Functional MRI data will be analyzed using a general linear model (GLM)-based approach and internalizing symptoms will be measured transdiagnostically via questionnaire. Behavior from the explore/exploit (reward learning) task will be modeled using the previously-validated SCEPTIC model, fit to the data using Bayesian approaches, and related to fMRI data using frequentist multilevel models. The proposed training plan leverages a world-class research environ- ment with a team of highly skilled mentors and consultants to provide the candidate with area knowledge in adolescent neurodevelopment and puberty and training in computational modeling and Bayesian statistics. In line with NIMH’s Strategic Objectives, the proposed work will characterize neurodevelopmental processes po- tentially amenable to behavioral and neural intervention with life-long benefits in internalizing disorders.

NIMH - National Institute of Mental Health

PROJECT SUMMARY/ABSTRACT Major Depressive Disorder (MDD) is associated with emotional memory deficits that have substantial downstream consequences, but treatment is limited by poor understanding of the upstream mechanisms driving such behavior. Our recent work applying the Drift Diffusion Model (DDM) suggests that depression disrupts emotional memory by increasing “old” evidence accumulation for both old and new negative material, indicating a negative bias specific to retrieval. The DDM can account for the negative retrieval bias in depression via two mechanisms: increased familiarity, in which depression strengthens evidence for all negative memories—even false ones; or motivated retrieval, in which depression increases the propensity for judging all negative evidence as “old”—even if it is weak. Thus, it is unclear whether depression affects the quality of negative memories or the way they are acted upon, limiting both basic and applied depression research. The proposed work distinguishes the familiarity vs. motivated retrieval accounts via the Parceling Recognition Into Strength and Motivation (PRISM) task, which isolates memory strength from decision processes by generalizing single-item recognition behavior to forced choices between targets and lures. The logic is elegant: Though a motivation to respond “old” can bias single-item judgments, it cannot play a role when judging which of two items is old; thus, familiarity is implicated when differences in accumulation rates extend across tasks, and motivation is implicated when they do not. By extending the PRISM task to emotional memory in depression, the PI seeks to more precisely characterize the negative retrieval bias, with the primary goal of identifying false familiarity vs. motivated retrieval as potential targets for basic and applied research (Aim 1). Moreover, the PI will build expertise in model-based neuroimaging (Goal 1) and curate a practical skill set in clinical research (Goal 2) by running a functional magnetic resonance imaging (fMRI) version of the PRISM task to identify brain areas supporting retrieval that are affected by depression (Aim 2). With substantial research and training opportunities available at McLean Hospital/Harvard Medical School, the mentorship of Dr. Dan Dillon (a well-established clinical neuroscientist), Dr. Courtney Beard (an outstanding translational researcher and licensed clinical psychologist), and Dr. Michael J. Frank (a renowned computational neuroscientist), with consultation from Drs. Jeffrey Starns (developer of the PRISM task), Dr. David Badre (a leading cognitive neuroscientist with expertise in fMRI), and Dr. Avram Holmes (an expert in large-scale brain networks focusing on emotion and cognition), the applicant will receive advanced training in career development, model-based fMRI, and translational research. Together, the proposed research and training plans will launch the PI into an independent research career focused on identifying neurocognitive treatment targets for depression.

National Institutes of Health

Neuromodulation/Neurostimulation Device Development for Mental Health Applications (R01 Clinical Trial Not Allowed)

National Institutes of Health

The purpose of this Notice of Funding Opportunity (NOFO) is to encourage applications seeking to develop the next generation of brain stimulation devices for treating mental health disorders. Applications are sought that will either 1) develop novel brain stimulation devices or 2) significantly enhance, by means of hardware/software improvements, the effectiveness of brain stimulation devices that are currently U.S. Food and Drug Administration (FDA)-approved or cleared. Novel devices should move beyond existing electrical/magnetic stimulation and develop new stimulation techniques capable of increased spatiotemporal precision as well as multi-focal, closed-loop approaches. Applications seeking to develop new capabilities should focus on significant enhancement of the spatial resolution, depth of delivery, and/or precision of the device. Incremental changes to existing devices (e.g., software updates) are not withinthe scope of this announcement.

National Institutes of Health

The purpose of this Notice of Funding Opportunity (NOFO) is to encourage applications seeking to develop the next generation of brain stimulation devices for treating mental health disorders. Applications are sought that will either 1) develop novel brain stimulation devices or 2) significantly enhance, by means of hardware/software improvements, the effectiveness of brain stimulation devices that are currently U.S. Food and Drug Administration (FDA)-approved or cleared. Novel devices should move beyond existing electrical/magnetic stimulation and develop new stimulation techniques capable of increased spatiotemporal precision as well as multi-focal, closed-loop approaches. Applications seeking to develop new capabilities should focus on significant enhancement of the spatial resolution, depth of delivery, and/or precision of the device. Incremental changes to existing devices (e.g., software updates) are not withinthe scope of this announcement.

National Institutes of Health

<p>The purpose of this Notice of Funding Opportunity (NOFO) is to encourage applications seeking to develop the next generation of brain stimulation devices for treating mental health disorders. Applications are sought that will either 1) develop novel brain stimulation devices or 2) significantly enhance, by means of hardware/software improvements, the effectiveness of brain stimulation devices that are currently U.S. Food and Drug Administration (FDA)-approved or cleared. Novel devices should move beyond existing electrical/magnetic stimulation and develop new stimulation techniques capable of increased spatiotemporal precision as well as multi-focal, closed-loop approaches. Applications seeking to develop new capabilities should focus on significant enhancement of the spatial resolution, depth of delivery, and/or precision of the device. Incremental changes to existing devices (e.g., software updates)are not within the scope of this announcement. Applications should be submitted by multi-disciplinary teams with a variety of expertise including systems neuroscience, engineering, clinical, and regulatory affairs.</p>

National Institutes of Health

The purpose of this Notice of Funding Opportunity (NOFO) is to encourage applications seeking to develop the next generation of brain stimulation devices for treating mental health disorders. Applications are sought that will either 1) develop novel brain stimulation devices or 2) significantly enhance, by means of hardware/software improvements, the effectiveness of brain stimulation devices that are currently U.S. Food and Drug Administration (FDA)-approved or cleared. Novel devices should move beyond existing electrical/magnetic stimulation and develop new stimulation techniques capable of increased spatiotemporal precision as well as multi-focal, closed-loop approaches. Applications seeking to develop new capabilities should focus on significant enhancement of the spatial resolution, depth of delivery, and/or precision of the device. Incremental changes to existing devices (e.g., software updates)are not within the scope of this announcement. Applications should be submitted by multi-disciplinary teams with a variety of expertise including systems neuroscience, engineering, clinical, and regulatory affairs.

National Institutes of Health

Neuromodulation/Neurostimulation Device Development for Mental Health Applications (R21 Clinical Trial Not Allowed)

NIMH - National Institute of Mental Health

Project Summary Across the 30 years (1992-2022) of our previous TG, Brandeis built a multi-disciplinary program encompassing faculty in Biology, Biochemistry, Chemistry, Mathematics and Psychology. We educate students (who themselves come from the same breadth of scientific backgrounds as our faculty) in the full range of Neuroscience topics from the molecular biology of neuronal non-coding RNAs to the cognitive effects of aging. Our tight-knit faculty collaborates across this range: each lab PI collaborates with multiple others, and most projects involve several levels of analysis. Our students are integral agents of this intellectually and spatially tight-knit neuroscience community, in that they typically work across more than one lab. The cohesion that results from this collaborativity is reflected in every aspect of the program—in coursework, rotations, thesis supervision, the shared availability of advanced instrumentation and the collegiality of interactions. The breadth of opportunity and interaction that characterizes Brandeis, and the close attention we pay to student progress, means that each student develops according to their individual needs, which in turn results in a very low attrition rate. Our students graduate with excellent credentials and go on to obtain positions in academia, health care, government and industry, and to directly contribute to the NIH mandate to benefit human health. A strong, abiding aspect of our program has always been our emphasis on quantitative thinking. Every area of Neuroscience is increasingly driven by large data sets; to be prepared for the myriad available careers in Neuroscience, students must become generally expert in the analysis of complex multivariate data. For this proposal, we evolve our approach to quantitative literacy, proposing extensive curricular changes that will ensure that our students graduate grasping the fundamentals of quantitation (rather than just knowing specific methods). Armed with an understanding of computational tools and programming, all of our students will have a solid foundation upon which to do rigorous research at any level of analysis. Program changes instituted for this proposal will ensure that the program of course work, rotations, multiple small-group colloquia, proposition exams, and participation in teaching does not keep our trainees from digging into their dissertation work before the end of Year 1. Laboratory research is not the sole focus of the first (or even 2nd) year at Brandeis, and our students are not supported on research grants in these critical first years. This training grant provides crucial funding to support students while they develop a broad set of intellectual skills. There are 20 mentors in our program and we are requesting funds for 8 trainees.

New Jersey Department of Human Services

NJDHS funds nonprofits and community organizations providing social services including mental health, substance use treatment, disability services, food assistance, and support for vulnerable populations across New Jersey.

Labor

On October 21, 2021, New York State (NYS) Governor Kathy Hochul announced a commitment of $11.1 million in federal workforce development investment to expand the Disability Resource Coordinators (DRCs) network across several Local Workforce Development Areas (LWDAs). This program builds on previous programs like the Disability Employment Initiative (DEI) and Disability Program Navigator, and aims to improve education, training and employment outcomes for individuals with disabilities, including those receiving Social Security benefits, by scaling up services and enhancing support across nearly all LWDAs in NYS.A key partner in the NY SCION effort is the New York Employment Services System (NYESS) under the NYS Office of Mental Health (OMH), which commits $1 million annually to support employment services in participating LWDAs for individuals with disabilities. Through this collaboration, DRCs connect individuals with disabilities to Career Center services, employment referrals, and benefits advisement. NY SCION is currently active in 27 LWDAs, including New York City, covering 48 counties, and has helped more than 11,000 individuals with disabilities access career services to date. The program's ambitious goal is to serve 45,000 individuals with disabilities, significantly improving access to sustainable employment and career pathways.

NIDA - National Institute on Drug Abuse

Project Summary/Abstract The “Opioid Crisis Response Act of 2018” is a key legislative effort to address the opioid epidemic in United States, recognizing opioid overdoses as one of the nation’s most pressing public health threats. Opioid related deaths have surged since 1999, with over 82,000 deaths in 2022 alone, driven primarily by synthetic opioids like fentanyl. To combat this crisis, there is an urgent need for new translational tools and strategies to better understand the neurobiology of opioid addiction. The mu opioid receptor (MOR) plays a critical role in regulating the respiratory system and neuropsychiatric functions, directly impacting the key concerns of the opioid epidemic – respiratory failure and addiction. Despite its importance in various diseases, the full scope of its role of MOR and its ligands in complex addiction mechanism in human brains remains unclear. To address this, we are developing a new translational tool to study the molecular and cellular mechanisms of receptor dysregulation that contribute to substance abuse and mental health disorders. Non-invasive, quantitative positron emission tomography (PET) imaging of MOR in the human brain will provide crucial perspective into how MOR density and occupancy are linked to its dysregulation. While a handful of conventional MOR-PET probes exist and offer valuable insights through preclinical and clinical imaging studies, they are either too potent or not sensitive enough for studying neurobiology of MOR in the living brain. This proposal focuses on the final preclinical evaluation of a safe, widely accessible PET neuroimaging probe18F-fluorocarfentanil (18F-FCFN). Our team recently developed four derivatives of 18F-FCFN and validated their in vivo suitability as PET neuroimaging probes in rats through proof-of-concept studies. Based on our prior findings, published in 2025, two 18F-FCFN candidates emerged with promising features – high brain uptake, favorable selectivity and specific binding to MOR. We now propose completing final evaluations in higher species to select the best 18F-FCFN candidates for clinical translation. In AIM 1, we will assess the in vivo pharmacokinetics, selectivity, and binding potential (BPND) of these two 18F-FCFN candidates in non-human primates (NHPs) and select the top candidate for further evaluations. In AIM 2, we will determine the whole-body biodistribution and radiation dosimetry of the selected 18F-FCFN candidate in NHPs, along with conducting acute toxicology studies to assess its safety for human use. This work is critical for selecting and advancing the top 18F-FCFN candidate to first-in-human trials.

NHLBI - National Heart Lung and Blood Institute

PROJECT SUMMARY The lack of non-invasive, real-time assessments of circadian rhythm metrics hinders the translation of circadian rhythm knowledge into clinical practice. Circadian rhythms are internal physiological processes that cycle every ~24 hours. Light is the most potent stimulus for circadian rhythm entrainment to environmental time. Misalignment of the circadian system with environmental time increases the risk of both chronic diseases (e.g., cardiovascular disease, obesity) and acute mental and physical health impairments, underscoring the need for accessible clinical assessment tools. The mechanisms underlying individual variability in circadian (mis)alignment are unclear; one potential mechanism would involve variations in how light is processed in the eye. This project will test the hypothesis that differences in multiple metrics of pupillary response to light stimuli will correlate with differences in circadian metrics – and be a potential biomarker for individual differences. Wavelength, duration, and intensity of light differentially affect the response of retinal image-forming (e.g., rods, cones) cells and non-image-forming (NIF) intrinsically photosensitive retinal ganglion cells (ipRGCs) that contain melanopsin. The NIF pathway is crucial for circadian entrainment to environmental time and impacts the pupillary light reflex, melatonin concentrations, and other physiology. Variations in the post-illumination pupillary response (PIPR), an ipRGC- linked response, have been linked to neurological conditions, including circadian rhythm sleep-wake disorders (CRSWD), suggesting that pupillary response could be used as a potential non-invasive close-to-real-time diagnostic and monitoring tool. Relationships between pupil responses during and after light stimuli and circadian timing metrics should be established. Our specific aims are to quantify (i) different metrics of pupil response during and after light stimuli of various intensities, wavelengths, and durations (ii) and their relationships with dim-light melatonin onset (DLMO, the current gold standard measurement for circadian phase) (Aim 1) and in individuals with two intrinsic circadian sleep-wake phase disorders (CSWPD) with altered sleep timing (Aim 2). An outpatient week of monitoring of sleep timing will be immediately followed by the inpatient protocol for both participant groups (Aim 1, healthy controls, leveraging a funded R01 experiment; Aim 2: Individuals with CRSWD funded with the F32 funds). The inpatient protocol will consist of multiple pupillometry sessions and an evening saliva collection for DLMO. During pupillometry, participants will be exposed to wavelengths of light designed to target the ipRGC cells (blue light) or not (red light) with a matched number of photons of different intensities and durations. This F32 award will incorporate training in the measurement and analysis of physiological measures, circadian rhythms, and photobiology, phenotyping of people with CSWPD, advanced statistical training, grant and manuscript writing, scientific communication, and lab management. Establishing a strong foundation in these areas will facilitate Dr. McCullar’s transition to an independent scientist uniquely poised to establish outpatient testing that provides non-invasive close-to-real- time assessments of circadian metrics that can be used to evaluate and monitor individuals with circadian (or other NIF- linked) pathologies, as well as tools to help facilitate the integration of circadian system monitoring into clinical practice.

NIMH - National Institute of Mental Health

Project Summary Recent genetic studies of intellectual disability (ID), autism spectrum disorder (ASD), and epilepsy (EPI) have revealed a significant association of these disorders with genes encoding proteins involved in glutamatergic synapse structure and function. One key protein known to regulate glutamatergic synapses is SynGAP1, a RasGAP critical for synaptic plasticity, learning, memory, and cognition. Deleterious mutations in SYNGAP1 in humans result in intellectual disability, autistic-like behaviors, and epilepsy. Knock-in model mice with mutations found in humans and heterozygous Syngap1 knock-out mice exhibit deficits in synaptic plasticity, learning, and memory, as well as seizures. We have recently discovered that the catalytic activity of SynGAP1's GAP domain is not required for synaptic plasticity and normal behavior in mice. Instead, SynGAP1 plays a unique structural role at the synapse, forming complexes with synaptic scaffolding proteins and dynamically regulating synapse structure and function. In addition, we have recently discovered that the mRNA splicing of the α1 splice variant of SynGAP1, the most significant isoform of SynGAP1 for synaptic complex formation and synaptic plasticity, occurs through a unique non-canonical splicing mechanism. Here, using a combination of molecular biological, biochemical, cell biological, and in vivo studies, we propose to investigate the structure and function of SynGAP1 critical for synapse complex formation, synaptic plasticity, and cognition. Moreover, using molecular biological, cell biological, and in vivo studies, we will characterize the molecular mechanisms underlying the unique noncanonical splicing of SYNGAP1 required for synapse complex formation, synaptic plasticity, and cognition. These studies will not only reveal novel mechanisms underlying the regulation of SynGAP1 function but will also uncover new pathways and candidates for therapies to cure SYNGAP1-related Intellectual Disability (SRID) and other SynGAP1-related disorders.

NIMH - National Institute of Mental Health

PROJECT SUMMARY/ABSTRACT Sensory processing difficulties are one of the biggest challenges to daily life for individuals with autism spectrum disorder (ASD). Sensory reactivity can be considered a biological response to sensory stimuli, for which individuals can vary continuously from low to high responses, for example in terms of heart rate reactivity or neural responses. We hypothesize that sensory over-responsivity (SOR), an extreme negative behavioral or affective response to everyday stimuli, emerges from early alterations in sensory reactivity and may be detected in the first six months of life. Understanding and identifying SOR emergence early in life has important implications for early intervention and limiting the extent to which SOR impairs other key developmental processes, such as social and language development, participation in school and the community, and overall well-being. Yet very few standardized, behavioral measures of SOR exist across the lifespan, and to our knowledge, no such measure exists for infants in the first 6 months of life, when these essential functions are in a key period of development. We propose to fill this critical research gap by identifying physiological (heart rate) responses to sensory stimuli and testing our hypothesis that atypical biological sensory reactivity is present and measurable before clear behavioral responses to sensory stimuli emerge. First, we will examine two existing datasets to: 1) identify candidate physiological markers of SOR in 3-month-old infants at low (LL) and elevated (EL) familial likelihood for ASD and 2) examine longitudinal changes in behavioral responses to sensory stimuli during a standardized sensory task in LL and EL infants between 6-24 months. Then, we will develop and pilot a series of standardized, naturalistic prompts that can be used to study physiological responses to aversive sensory stimuli in the first 6 months of life. Identification of physiological markers of SOR in the first 6 months would promote earlier detection of atypical development, with implications for supporting infants with atypical sensory reactivity much earlier in life, before the core features of ASD emerge.

NIMH - National Institute of Mental Health

Abstract Despite the effectiveness of antiretroviral therapies (ART) in reducing systemic HIV viral loads, central nervous system (CNS) dysfunction remains prevalent in 30-50% of people living with HIV (PWH). ART does not eliminate viral reservoirs in the CNS, leading to chronic neuroimmune dysfunction and conditions like HIV-associated neurocognitive disorder (HAND). Current preclinical research has primarily focused on models that simulate acute HIV infection, but there is a pressing need for models that accurately reflect CNS dysfunction in the context of chronic ART-suppressed infections. Recent advancements in immunodeficient mouse models with humanized immune systems have shown promise, allowing for natural HIV infection and crossing of the blood-brain barrier. These models have provided insights into HIV infection in the CNS and the role of human microglia cells. However, significant gaps remain, particularly in developing models that incorporate multiple human CNS cell types and accurately represent chronic infection dynamics. This proposal aims to develop preclinical NeuroHIV models that better mimic CNS-immune interactions in general and in particular during ART suppression. Specifically, our goal is to develop the next generation NeuroHIV model composed of autologous peripheral human immune cells, relevant human glial cell types, and an intact blood-brain barrier all in the context of ART-mediated HIV suppression.

NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development

Maternal prenatal stress and nutrition influence fetal growth and long-term child outcomes. Maternal perceived stress and undernutrition frequently co-occur and affect overlapping biological stress pathways related to oxidative stress, Still, little is known about the interactive effects of maternal prenatal stress and nutrition on fetal and long-term child outcomes and neurological development. The proposed R00 research will leverage data from the “Enhancing Nutrition and Antenatal Infection Treatment for Maternal and Child Health” (ENAT) trial to examine interactive effects of maternal prenatal stress and nutrition intervention on long-term child outcomes. The ENAT study randomized n=2390 pregnant women to receive an “enhanced nutrition” package or “standard care” and collected data on maternal prenatal stress (Cohen’s Perceived Stress Scale) throughout the pre- and postnatal period. Using data from ENAT, we will determine independent and interactive effects of maternal prenatal perceived stress and nutrition intervention on children’s cognitive and neural developmental at 24 months of age. Child outcomes will include stress-sensitive outcomes previously shown to be sensitive to early life adversity, including attention, memory, and language. We will also use electroencephalography (EEG) to examine neural oscillation across different frequency bands as an index of neural maturation. To study underlying biological pathways, we will use maternal and infant blood samples examine whether maternal and newborn telomere lengths may serve as biomarkers of in-utero programming of birth and child outcomes in relation to maternal prenatal perceived stress and nutrition. We hypothesize that higher levels of maternal prenatal stress will be associated with poorer cognitive and neural oscillatory child outcomes. Telomeres are non-coding tandem repeats at the end of the chromosomes that maintain genome and cell integrity. Telomeres erode over time and stress and poor nutrition can lead to accelerated erosion and cellular aging. Children with low birthweight have been found to have shorter telomeres. We therefore hypothesize that effects of prenatal stress on birth and child outcomes will be mediated by maternal and newborn telomere length, but that such associations will be attenuated in offspring of women who received nutrition intervention This R00 will enable me to lead an innovative research program in child neurodevelopment and establish me as a leader and innovative scholar utilizing advanced methods to uncover mechanistic processes that shape childhood development in domestic and global settings. The proposed research aligns with NICHD’s goal to set a foundation for healthy pregnancies and lifelong living. We will generate epidemiologic and biologic evidence linking maternal prenatal nutrition and stress with newborn and childhood outcomes that are sensitive to prenatal stress and form long-term outcomes related to school achievement and mental health. We will use this knowledge to guide public health decisions regarding pre- and postnatal intervention both domestically and globally, and to develop future intervention to support optimal child development and health.

NIA - National Institute on Aging

PROJECT SUMMARY As the burden of Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD) grows, understanding how occupational factors impact brain and cognitive health is critical. However, research on the role of occupational stimulation, such as occupational complexity, remains inconclusive, and the impact of occupational stressors on cognitive and brain health has yet to be explored. Jobs with repetitive tasks, low autonomy, and high physical demands may contribute to cognitive decline, brain atrophy, and increased dementia risk. Furthermore, there is a lack of evidence on how these factors specifically impact US Latinos, who are often employed in low-wage occupations and face a higher risk of AD/ADRD. Understanding how occupational stressors and complexity affect cognitive and brain aging among US Latinos, is crucial. The overarching research objectives of this proposal are: (1) to investigate how physical and mental occupational stressors affect mid-life cognitive function in US immigrant Latinas in rural and semi-rural areas – an underrepresented group in research, and (2) to disentangle the effects of occupational complexity from physical occupational stressors on brain and cognitive health in US Latinos, considering effect heterogeneity by Latin American heritage, and US nativity. The central hypothesis is that higher occupational complexity promotes cognitive and brain health, but occupational stressors may outweigh benefits. To address these objectives, I will (1) estimate the longitudinal effect of physical and mental occupational stressors from early adulthood to midlife on cognitive function; (2) estimate the individual effects of physical occupational stressors and occupational complexity on AD/ADRD neuroimaging biomarkers and (3) estimate the individual and joint effects of hypothetical interventions on physical occupational stressors and occupational complexity on cognitive function, cognitive decline, and mild cognitive impairment, and evaluate effect heterogeneity by sex, Latin American heritage, and US nativity. I will use data from two NIA-funded studies: (1) Center for the Health Assessment of Mothers and Children of Salinas Maternal Cognition Study and the Hispanic Community Health Study/Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA), and ancillary study SOL-INCA-MRI. Under the guidance of a multidisciplinary mentorship team, the accompanying training plan builds on my background in medicine, epidemiology and statistical methods with additional training in (1) occupational epidemiology; (2) measuring and modeling cognitive function on Spanish-speaking/bilingual communities; (3) neuroimaging biomarkers for AD/ADRD research. The combined research and training plans will prepare me to become a successful researcher integrating clinical expertise, cutting-edge epidemiologic methods, and social science theories to understand social drivers of AD/ADRD. The findings will uncover the mechanisms linking occupational exposures and AD/ADRD and inform interventions and policies to reduce AD/ADRD by improving working conditions.

Labor

Funding will be provided to Local Workforce Development Boards (LWDBs) for the up-skilling or re-skilling of workers transitioning from fossil fuel to clean energy positions; the up-skilling or re-skilling of residential workers in weatherization, building performance, and retrofitting, including fees required for industry-recognized credentials; and wraparound services during training, including but not limited to, childcare, transportation, housing, food, mental health services, and substance use treatment or services.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY Chronic obstructive pulmonary disease (COPD) is characterized by decreased lung function and increased inflammation, punctuated by periods of increased coughing and shortness of breath known as exacerbations. Exacerbated COPD results in not only a hastening of lung decline but also a decline in the quality of life and mental health of patients. The obligate human pathogen nontypeable Haemophilus influenzae (NTHi) is the primary cause of exacerbated COPD, responsible for a minimum of ~30% of all exacerbations. The macrolides azithromycin and clarithromycin are predominantly prescribed to treat NTHi-complicated COPD due to its broad activity and immunomodulatory effects that decrease inflammation and the prevalence of future exacerbations. However, due to intrinsic factors and acquired mutations, macrolide treatment is becoming less effective against this bacterial pathogen. The primary objective of this proposal is to optimize the current treatment method for NTHi-exacerbated COPD by addressing established macrolide resistance and the ability to gain macrolide resistance while maintaining the benefits of macrolides. We performed a Tn-Seq screening to identify genes necessary for intrinsic resistance to clarithromycin and cross-referenced the results with those of another screening our lab performed for genes necessary for infection in the murine lung to explore the idea that drugs targeting proteins with dual requirements for both conditions would restore sensitivity to resistant strains and would constrain potential escape mutations. We characterized the gene encoding for the outer membrane protein Omp26, homolog of the E. coli periplasmic chaperone Skp, and found that deletion of omp26 resulted in susceptibility to clarithromycin in strains overexpressing the macrolide efflux pump AcrAB and that Omp26 plays a role in resistance to the human complement system. I hypothesize that targeting macrolide intrinsic resistance factor Omp26 in NTHi can be exploited to make NTHi more sensitive to macrolides and to host immune clearance mechanisms and potentially restore macrolide sensitivity to resistant strains. Experiments proposed in Aim 1 will investigate the function of Omp26 by defining its role in serum resistance, examining how it contributes to the composition of outer membrane proteins, and performing a survey of the necessity of Omp26 for infection in the murine lung across multiple strains of NTHi. Aim 2 will address the effect Omp26 has on major lung virulence associated phenotypes including heavy metal resistance, acquisition of host-sequestered nutrients, and resistance to oxidative stress. Finally, the experiments proposed in Aim 3 will determine the efficacy of targeting Omp26 in macrolide resistant clinical NTHi isolates with ribosomal mutations. Collectively, this data will contribute to further studies in the role periplasmic chaperones play in virulence and provide the framework necessary for the designing of in vitro assays based on the identified mechanisms of Omp26 to screen for future drugs for the treatment of nontypeable H. influenzae-exacerbated COPD.

NYS Office of Mental Health

4340 ? Ongoing Integrated Supported Employment Services (Non-Licensed Program) These services are allocated for specific individuals who have achieved job stabilization though ACCES-VR intensive employment services and are designed to provide ongoing supports to overcome mental health challenges in order to sustain integrated, competitive employment, or support for promotion or to find new employment. The goal of supported employment is for individuals to work a minimum of 10 hours per week in an integrated, competitive job, with leeway for absence due to illness, vacation, or temporary work stoppages. See Glossary for definitions of "Competitive Employment" and "Integrated Employment". To be considered employed part time, participants should be scheduled to work a minimum of 10 hours each week. Units of Service: Count the total number of staff hours.

NIMH - National Institute of Mental Health

Project Summary Suicide is currently the second leading cause of death amongst adolescents. Interpersonal dysfunction is a significant risk factor for suicidal thoughts and behaviors (STBs), but it is primarily assessed through self-report methods that are inherently problematic due to subjective retrospective recall bias. By depending on self-report of interpersonal functioning, we overlook crucial information about how at-risk youth are interacting with others. To address these gaps, this K23 proposes mentorship in online social networking (OSN) as an objective, ecologically valid assessment of interpersonal behavior (i.e., texting, engagement on social media) in adolescents with STBs. The research aims of the study are to (1) establish active online interpersonal behavior mechanisms in adolescents with STBs, (2) determine passive online interpersonal behavior mechanisms in adolescents with STBs, and (3) identify mediators (e.g., psychopathology, biological sex) relevant to the relationship between OSN and STBs. Multimodal data (OSN, self/parent/clinician report) will be collected from N=84 13–17-year-olds, with the full range of STBs. One month of active (i.e., texting/posting frequency) and passive (i.e., ratio of time spent on apps to texting, inter-day app/platform switching) OSN data will be collected from adolescents’ smartphones and analyzed using mentored statistical approaches to multimodal data including structural equation modeling (SEM). The candidate proposes training in (1) use of OSN as a real- world assessment of interpersonal functioning behaviors in adolescents, (2) gaining expertise in the relationship between STBs and OSN in adolescents, and (3) gaining skills with relevant multimodal data analysis (e.g., SEM) to understand what psychosocial factors may mediate OSN behavioral mechanisms and suicide risk. A team of multi-disciplinary mentors bring expertise in adolescent developmental psychopathology, computer science, interpersonal functioning, and translational research. Combined with the relevant and diverse resources available at McLean Hospital and Harvard Medical School will ensure this candidate receives the necessary training and support to successfully complete the project and launch the candidate’s career in adolescent suicide prevention. Data will directly inform future R01s leveraging this information to prevent suicide risk in adolescents, including (1) probing diagnostic/assessment specificity, (2) using experimental therapeutics to evaluate change in detected interpersonal behavior mechanisms following established evidence-based treatments for STBs, and (3) the development of mechanism-informed just-in-time adaptive social media/mobile health interventions. Completion of the proposed research and training goals will uniquely position the candidate to become a leader in the highly relevant field of adolescent social media and suicide prevention.

NIMH - National Institute of Mental Health

PROJECT SUMMARY The mammalian brain has up to 100 trillion synapses, representing an immense potential reservoir for information storage. Most theories of memory storage in the brain assume that memories are stored by changes in synaptic strength but, despite decades of work on synaptic plasticity and neuromodulation, and tantalizing progress the best understood mechanisms that change synaptic strength have yet been shown to underlie memory storage in the intact brain. A key reason is the challenge of measuring and manipulating synaptic strength at identified synapses at the population scale during learning. These challenges can now be addressed by new technologies for imaging and manipulating synaptic function at scale during behavior. We propose here to make a major advance in synaptic manipulation. Optogenetics has revolutionized neural circuit analysis by enabling stimulation or inhibition of action potential firing in select neurons. Chemical optogenetics has extended optical control to the synapse by enabling light- activation and ilght-block of the receptors that mediate synaptic transmission, plasticity and neuromodulation. Synthetic photoswitches have been developed to control ionotropic receptors for fast signaling and G protein coupled receptors for neuromodulation. The number of receptors has expanded greatly in the past 5 years, and there has been great success in using these in the brain of awake behaving animals from flies to fish to mouse. We propose to make a quantum leap in the precision of synapse control through new schemes for targeting optical control of receptors to specific synaptic compartments and specific classes of synaptic connections. Each neurotransmitter has multiple receptors, creating great complexity. The difficulty for analysis is increased by the fact the same receptor may be found on multiple cells in a circuit and, in fact, in more than one location in a particular cell, with distinct function at each location. Our method enables us to selectively control receptors in a genetically selected manner. We now add the ability to restrict control to one compartment in the cell: say the presynaptic site, where transmitter release is regulated, or the postsynaptic site, where the response to transmitter is regulated. We add to this, methods for enhancing penetration of control light through brain tissue— a key step to reduce invasiveness of implanted fiber optics and to ease the transition of the application to larger brains. The project is made possible by an inter-disciplinary collaboration between molecular and cell biologist Isacoff and synthetic chemist Trauner, who co-developed chemical optogenetics have collaborated extensively since, physical chemist Cohen, a pioneer in upconverting nanoparticles that turn IR light into visible light, and circuit neuroscientist Lammel, an expert in optogenetic and behavioral analysis.

National Institutes of Health

This Notice of Funding Opportunity (NOFO) invites applications from clinical centers to participate in a consortium to test anti-obesity medication (AOM) treatment strategies for youth with obesity that maximize benefits and minimize risks of AOM use. Such intervention strategies should support the promotion of healthy growth and development; adequate nutritional status/intake, healthy eating and physical activity behaviors; mental health and well-being (e.g., body image, self-esteem, mood, etc.), and quality of life and be feasible to implement in clinical care settings. Priority areas include testing strategies to determine optimal developmental stage for AOM initiation, rate and amount of weight loss, AOM class, dose, frequency, and duration, and content and intensity of adjunct lifestyle therapies that may be imperative to ensure normal psychological and physical development and to potentially avoid lifelong dependence on AOMs. Investigators should also evaluate potential predictors of response/ nonresponse to various treatment strategies under evaluation. The clinical centers may conduct independent or multicenter trials but will collaborate on the development of protocols, use of common measures and data elements, use of a central laboratory and standardized procedures to collect data and biospecimens, and data analyses and manuscripts. This NOFO uses a cooperative agreement mechanism (U01) and runs in parallel with a companion NOFO (RFA-DK-27-136).