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Role of dopamine in neuroimmunoendocrine mechanisms of spontaneous preterm birth

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

SUMMARY Reliable tools for early prediction and effective treatments of spontaneous preterm birth (sPTB) are missing. This is due to an incomplete understanding of the subclinical pathobiology preceding sPTB. The long-term goal of this project is to integrate pathological, physiological, and psychological domains preceding sPTB to define mind- body crosstalk mechanisms that enable robust sPTB prediction and reveal potential targets for therapeutic intervention. The overall objective in this application is to establish neuroimmunoendocrine pathways as critical modulatory links between maternal mental state, immune imbalance, and sPTB. The central hypotheses are that (i) catecholaminergic (i.e., dopaminergic) signaling in maternal central and peripheral systems mitigates inflammation-induced parturition, supporting pregnancy maintenance, and that (ii) disruptions in neuroendocrine signaling may underlie an immune shift in the maternal circulation as well as at the maternal-placental interface promoting sPTB. The central hypotheses will be tested by pursuing three specific aims: 1) Determine whether central dopaminergic activity mitigates inflammation-induced PTB in mice; 2) Define predictive neuroimmunoendocrine trajectories of sPTB and their placental inflammatory signatures; and 3) Determine the effect of dopamine on the human maternal-placental interface, comparing sPTB vs. TB. Under the first aim, an established murine model of PTB will be combined with targeted neuromodulation of central reward circuitry to evaluate the effect on birth timing and peripheral immune state. In the second aim, human pregnancies at risk for sPTB will be longitudinally evaluated for multiple psychological (psychometric surveys, allostatic load) and physiological (blood immune function, non-invasive urine markers, cerebrospinal fluid markers, placental pathology) domains to define mind-body crosstalk prior to and at manifestation of clinical parturition pathology. In aim three, human endometrial stromal cells will be used to identify and causally link the effect of catecholamines on inflammatory signaling, differentiation, and protein secretion at the maternal-placental interface. The research proposed in this application is innovative because it represents a substantive advancement from the status quo by defining the basic principles of the maternal brain–immune–reproductive system axis in healthy pregnancies and those complicated by sPTB. The proposed research is significant because it is expected to offer a strong scientific framework whereby new strategies for the clinical management of patients at risk for sPTB can be developed.

Up to $658K
2031-02-28
health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Role of Two Medial Prefrontal Long-Range Recurrent Networks in Behavior Initiation and Inhibition

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NIMH - National Institute of Mental Health

Abstract The medial prefrontal cortex (mPFC) is critical for executive function, yet how its dorsal (dmPFC) and ventral (vmPFC) motor-projecting (MP) neurons coordinate behavioral initiation, inhibition, and cognitive flexibility remains poorly understood. This R21 leverages four translational behavioral paradigms (head-fixed Persistent Licking/Shock-Escape; freely moving FED3-based Reversal Learning/Stop-Signal), high-density neural recordings, circuit manipulations, and Brian2 spiking neural network modeling to test our central hypothesis: dmPFC MP neurons drive action initiation and adaptive switching, while vmPFC MP neurons suppress impulsivity and perseveration. In Aim 1a, we quantify behavior using kinematic analyses (jerk, velocity, z-scored) aligned with human executive dysfunction metrics (Action Latency [AL], Reversal Accuracy [RA], Perseveration Errors [PE], Stop-Signal Reaction Time [SSRT]), combined with optogenetic (stGtACR2/ChR2) and chemogenetic (PSAM/varenicline) perturbations. Aim 1b employs optotagging and population analyses (PCA, SVM, Total Spiking Probability Edges) to decode dmPFC/vmPFC MP dynamics across tasks, resolving specialized versus mixed functional roles. Aim 1c integrates these datasets into Brian2 spiking network models to predict neural-behavioral correlations, validated through cross-validation. Exploratory analyses will link murine kinematic signatures to human stop-signal/reversal learning metrics. By elucidating strain-specific (C57BL/6 vs. CD1) circuit mechanisms and delivering translatable biomarkers (AL, RA, PE, SSRT, kinematics), this work addresses a critical gap in understanding neuropsychiatric disorders like ADHD (impulsivity) and schizophrenia (perseveration). The study’s innovative combination of recurrent neural network theory, FED3-based assays, and New Approach Methodology (NAM)-compliant computational modeling pioneers high-risk, high-reward tools for circuit dissection, fully aligning with NIH’s 2025 priorities.

Up to $397K
2028-06-09
health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

SAFER: Suicide Assessment and Follow-up after Emergency Department Release for 8-12-Year-Old Children

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NIMH - National Institute of Mental Health

Project Summary Despite widespread prevention efforts, suicide is the second leading cause of death among teens and young adults, and increasingly, suicide has become a public health concern among children <12-years-old. The emergency department (ED) often serves as the primary contact point for youth to receive care for suicide risk. Yet, among adolescents receiving inpatient or ED care, 10% will attempt suicide and 30% will exhibit suicidal behaviors within 3 months of discharge. This study aims to map the landscape of early suicide risk among children seeking ED care to facilitate the development of actionable intervention targets/methods. We will recruit N=250 children (8-12 years old) via multiple pediatric EDs (NewYork-Presbyterian, Montefiore) with diverse catchment areas and patients with typically less access to care. Children and their guardian will complete clinical interviews to probe suicide and related risk factors. Electronic health records will be probed for structured data on risk factors as well as using natural language processing of clinician notes. Children will also complete brief MRI scanning at baseline to assess brain structure (using clinically relevant MRI protocols) and midbrain dopamine (novel neuromelanin MRI). We focus on brief, clinically relevant sequences that are readily harmonized across site/scanners and can be assessed from brain imaging ordered as part of clinical practice. During a 6-month follow-up period, guardians will complete low-burden, weekly check-in surveys (via their personal smartphone) as well as brief 3- and 6-month remote interviews to characterize fluctuations in their child’s suicide risk, difficulties with safety plans, changes in risk factors (e.g., sleep, familial disruptions, impulsive behaviors), and any subsequent of suicide behaviors. These multi-faceted data will be leveraged to examine clinical and neural risk factors that predict post- discharge suicide events (e.g., suicide attempts, return to ED, or psychiatric hospitalization) in high-risk children. Weekly parental reports will help to map post-discharge changes over 6 months related to suicide events post- discharge. We anticipate that greater psychiatric comorbidity, sleep problems, and family stress will be critical risk factors for post-discharge suicide outcomes. Further, smaller prefrontal, striatal, and cingulate volumes relative to population levels as well as reduced midbrain dopamine will predict greater risk for future suicide events. Difficulty implementing safety plans, maintaining regular routines (e.g., bedtimes, home environment), and excessive family conflict in the post-discharge period will relate to subsequent suicide events. This work will inform the development of new screening (to ensure that key risk factors are clearly ascertained and documented), improve discharge plans for clinicians, and help families detect risk post-discharge. Improving care for high-risk young children is an urgent priority. Findings from this work may be able to address suicide risk in other settings (e.g. primary care) and populations.

Up to $868K
2031-02-28
health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Scaling Up Services to Support Early Autism Identification: What Key Services Predict Earlier Diagnosis?

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NIMH - National Institute of Mental Health

Reducing the age at autism diagnosis is a crucial public health priority, as early diagnosis is associated with better developmental and mental health outcomes. Though autism can be reliably diagnosed in children as young as fourteen months, the average age at diagnosis in the United States is around four to five years. Documented differences in diagnostic timeliness exist by sociodemographic features. However, more research is needed on the modifiable, or scalable, aspects of the service system that can facilitate earlier access to autism diagnosis. Autism screening in primary care holds promise to reduce the average age at diagnosis, as autism-specific screening and attendance at well-child visits are associated with earlier age at diagnosis. Yet, to date, no comparative studies have been conducted to understand the differences in diagnostic timeliness between those screened versus those not screened for autism in primary care. Optimizing early identification of autism in primary care is crucial, as primary care is often children’s entry point on their pathway to a diagnosis. Of parallel importance, more research is needed on children’s complete pathway through services to the receipt of a diagnosis so that optimal pathways that facilitate earlier diagnosis can be identified. Therefore, the present study aims to understand what services work and in what context to lower the age at autism diagnosis, with a particular focus on autism screening in primary care. Prior studies of age at diagnosis have been limited by an over-reliance on Medicaid claims data, retrospective caregiver-report, and analysis of discrete variables in relation to age at diagnosis (e.g., number of appointments). The present study leverages the MarketScan Commercial Claims Database—a national claims database comprised of over 10 billion records from 70 million privately insured individuals. The present study is the first to examine autism screening in primary care using claims data. Analyzing data from a sample of children diagnosed with autism in early childhood, we aim to: 1) evaluate the effect of autism screening in primary care on child age at autism diagnosis using propensity score matched samples, 2) compare the effect of autism screening in primary care on child age at diagnosis in resource-poor or resource-rich areas, and 3) discover service pathways to a formal autism diagnosis using discrete sequence clustering analysis. A highly experienced mentorship team of investigators will support the principal investigator’s research and training plan to further her independence as a behavioral health services researcher, with a focus on autism-related services. Through a combination of carefully curated training activities, the principal investigator will: 1) deepen her understanding of autism-specific service disparities in early childhood and identify targets for intervention, 2) develop expertise in behavioral health services research methodology, 3) build mastery in administrative claims data management, 4) gain knowledge in rigorous analytic approaches for use in observational data, and 5) strengthen skills in scientific writing and related skills to bolster her independence as a scientist.

Up to $42K
2027-12-31
health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

SCH: Real-Time Engagement of Children for Individualizing Behavior Management with Wearables

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NIMH - National Institute of Mental Health

Approximately 4.5 million children in the United States (US) display severe emotional and behavioral disturbance. While it is not unusual for preschoolers to have occasional temper tantrums, it is considered symptomatic when temper outbursts (characterized by sudden, violent expression of strong feeling, anger, and aggression) occur most days that are severe enough to impair their academic, social, and family functioning. Evidence-based therapies such as parent child interaction therapy (PCIT) reduce behavioral challenges in children by improving parent-child relationships through parenting practices taught over a multi-week period. Despite the widespread availability of behavioral interventions, there are significant challenges: (a) the effectiveness of interventions is contingent upon parents remembering parenting practices taught during weekly therapy sessions to engage with their children, (b) there is limited education for affected children and their parents to help preempt temper outbursts and regulate their emotion, and (c) families from rural areas and populations with limited specialized pediatric mental health providers are less likely to have access to and utilize evidence-based therapies when it is available. The overarching goal of this convergent research proposal is to investigate the development of generative methods with closed-loop feedback from parents to individualize real-time interventions for children when a temper outburst is predicted. The project will accomplish the goal through the following aims. Aim 1: This project will develop generative algorithms with closed-loop feedback using 5.4 million minutes of smartwatch data collected from 50 children (aged 3 – 7 years) and parent-provided timestamps (closed-loop feedback) of disruptive behavior (characterized by temper outbursts). Aim 2: The developed technology will then be evaluated in a cohort of 50 new children to assess if parenting practices combined with child-initiated mindfulness (i.e., new patient-education) upon a predicted temper outburst could improve behavioral outcomes. Aim 3: Elucidate the perspectives of stakeholders (e.g., parents, schoolteachers) on the use of continuous monitoring devices for adaptive generative intelligence algorithms.

Up to $301K
2030-02-28
health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Screening the functionality of PTEN variants and pharmacological candidates in vivo

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NIMH - National Institute of Mental Health

PROJECT SUMMARY PTEN (Phosphatase and Tensin Homolog) is one of the strongest genes associated with autism spectrum disorders (ASDs) and one of the most highly pleiotropic. PTEN encodes a negative regulator of mTOR signaling – a central metabolic pathway controlling protein synthesis, cell growth, and survival, yet the mechanisms contributing to the considerable pleiotropy of PTEN mutations are not well understood. Here, we propose a highly innovative approach that leverages the unique features of zebrafish to illuminate basic neurodevelopmental mechanisms downstream of PTEN loss of function and rapidly screen the functionality of human PTEN variants and pharmacological candidates targeting these mechanisms. Our central goals are: (1) to screen the functionality of human PTEN variants in the developing vertebrate brain in vivo; and (2) to identify novel pharmacological suppressors of PTEN-associated phenotypes. Our central hypotheses are: (1) the in vivo functional effects of PTEN mutations will reveal novel genotype-phenotype correlations, expanding on existing in silico and in vitro analyses; and (2) targeting specific components of the mTOR pathway will selectively reverse these phenotypes. To test our hypotheses, we will perform in vivo zebrafish screens to assess the functionality of human PTEN variants in a developing vertebrate brain informed by multiple in silico and in vitro predictions (Aim 1); and conduct high-throughput pharmacological screens of mTOR-targeting compound libraries in zebrafish (Aim 2). Our team is uniquely suited to perform these experiments, given our complementary expertise in high-throughput zebrafish ASD gene mutant analyses (MPI Hoffman) and computational modeling of ASD gene variants (MPI Turner). The broader impact of this research is to establish a proof-of-principle for in vivo human variant and pharmacological screens in zebrafish and to illuminate basic mechanisms contributing to pleiotropy across neurodevelopmental disorder genes.

Up to $464K
2028-06-14
health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

SeeMe: A multimodal behavioral-electrophysiological tool for real-time detection of consciousness

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NIMH - National Institute of Mental Health

SeeMe: A multimodal behavioral-electrophysiological tool for real-time detection of motor behavior in brain injury patients Abstract An obstacle in clinical and basic science consciousness research is the lack of quantitative techniques to assess the recovery of voluntary behavior. Standard techniques for consciousness detection depend on subjective assessment of voluntary behavior. These methods are slow, observer-dependent, and lack the temporal resolution to study brain circuits supporting consciousness. In Phase R61 of this proposal, SeeMe, a novel, objective, real-time tool, will be developed to detect voluntary behavior. This multi-modal tool is based on the measurement of face and hand movements to command in recovering traumatic brain injury (TBI) patients who may appear unresponsive. SeeMe detects early signs of low-amplitude voluntary behavior currently unseen by clinical examiners. These detected movements will be linked with neural recordings to interrogate underlying circuits supporting voluntary behavior. This tool will be made freely available to researchers interested in consciousness and more generally studying brain-behavior relationships. Phase R33 will use SeeMe to time- lock vagus nerve stimulation to voluntary behavior in recovering TBI patients, analogous to its FDA-approved use in stroke. This framework will be used to study the neural correlates of voluntary behavior in TBI patients. When complete, this project will deliver 1.) a novel objective tool for analyzing voluntary behavior, 2.) a computational framework for synchronizing behavior with brain activity, and 3.) a closed-loop stimulation system to develop future neuromodulatory therapeutic approaches to facilitate the return of motor behavior after injury.

Up to $467K
2029-03-31
health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Self-Compassion, Health, and Empowerment: A Randomized Controlled Trial for Chinese Immigrant Women Experiencing Intimate Partner Violence

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NINR - National Institute of Nursing Research

ABSTRACT Intimate partner violence (IPV) poses significant social and health challenges, particularly affecting immigrant women who confront increased risk and adverse consequences. Chinese immigrants, the largest Asian ethnic group in the U.S., with over 4 million individuals, have received limited focus in existing IPV research and intervention efforts, despite a high prevalence of IPV reaching nearly 21% within the past year. They face substantial barriers to accessing IPV and mental health services, due to sociocultural factors such as stigma or shame, limited English proficiency, isolation from mainstream American society, unfamiliarity with available resources, and limited availability of linguistically and culturally appropriate services. Moreover, IPV’s substantial and well-documented effects on mental health further exacerbate the challenges faced by this population of women. However, there is a lack of culturally appropriate interventions that address these barriers while improving their acceptability and accessibility to address the mental health needs of abused Chinese immigrant women. To fill this gap, our proposed community-partnered intervention, Self-Compassion, Health, and Empowerment (SHE), adapts a structured safety and empowerment intervention while uniquely incorporating mental health elements, including relaxation and self-compassion meditation, to address abused Chinese immigrant women’s mental health needs. Leveraging mobile health technology, our intervention seeks to overcome barriers such as geographic dispersal, stigma, and privacy concerns that often hinder access to support. Our pilot randomized controlled trial (RCT) with 50 abused Chinese immigrant women has shown the feasibility and acceptability of the mobile-based SHE intervention, which forms the basis for this proposal of a fully powered two-arm RCT. The primary aim of the study is to test the efficacy of the mobile-based SHE intervention in improving mental health among Chinese immigrant women experiencing IPV and co-occurring symptoms of depression, anxiety, or posttraumatic stress disorder (PTSD). We will recruit 364 Chinese immigrant women and randomize them 1:1 to the intervention or attention control group. The 6-week SHE intervention consists of one phone session on IPV safety and empowerment and five weekly relaxation/self-compassion sessions via text. The attention control group will receive 6 weekly nutrition and health sessions, matched in delivery mode, timing, and contact frequency. We will compare the two groups for primary outcomes of depression, anxiety, and PTSD symptoms and the secondary outcome of IPV from baseline to 6-week, 3-month, 6-month, and 12-month follow-ups. Our findings will provide evidence for the application of the mobile-based SHE intervention to support the mental health needs of abused Chinese immigrant women. Our approach is innovative, and there is a high potential for scaling up the intervention to improve access to IPV and mental health support among Chinese immigrant women experiencing IPV.

Up to $638K
2031-02-28
health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Sensor-Based Intervention Modeling: A Personalized Tool to Support Intervention in Adolescent Mood Disorders

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NIMH - National Institute of Mental Health

Project Summary Mood disorders in adolescence are prevalent, disabling, and associated with future chronicity and severity of mood problems in adulthood, making this a developmental period in which effective early intervention is especially important. A critical common ingredient of many interventions for adolescent mood disorders is inter- session monitoring of behaviors and mood; such monitoring is used by patients and practitioners to support case conceptualization, identify patient-specific maladaptive behaviors, and evaluate treatment outcomes. However, adherence to inter-session monitoring is low among adolescents, undermining intervention effectiveness. To optimize and support delivery of effective interventions for adolescent mood disorders, we are in need of novel, low-burden strategies for monitoring behavior and mood. The proposed study aims to address this urgent need by validating and translating a novel smartphone-based intervention monitoring approach (Sensor-Based Intervention Monitoring, SBIM). Aims will be tested in an adolescent sample (n=33, ages 13-19 years) engaged in interventions for mood disorders through the Helen and Arthur E. Johnson Depression Center or the Child and Family Clinic at the University of Colorado Anschutz Medical Campus. Study participants will complete a baseline evaluation followed by an eight-week period of SBIM using smartphones to collect native digital sensors (e.g., GPS, accelerometer, log data of screen use, app use, call/text activity, and ambient light/sound) and ecological momentary assessment (EMA) of mood symptoms. Daily behaviors are measured by extracting behavioral features from digital sensors, and include sensor-based measures of behavioral activation, impulsivity, physical activity, social withdrawal, sleep/circadian disturbances, and goal-directedness. SBIM Reports, providing inter- session monitoring information about patient-specific behaviors, mood, and behavioral predictors of mood, are delivered to clinicians and patients biweekly. Clinicians and patients report on acceptability, appropriateness, and feasibility of SBIM, and treatment outcomes, biweekly. Aim 1 centers on rigorously validating SBIM, testing the predictive accuracy of personalized models and comparing personalized to general models. Aim 2 evaluates feasibility, appropriateness, and acceptability of SBIM for both patients and clinical providers, and Aim 3 tests convergent validity of SBIM with standard treatment outcomes. Exploratory Aim 4 explores subgroups to compare differences in SBIM outcomes between interventions (behavioral, medication management), diagnoses (unipolar, bipolar) and as a function of sex, age, or pubertal stage. Ultimately, we aim that this work will develop and validate a novel monitoring tool and explore translation to the clinic, providing a foundation for research that scales and investigates SBIM outcomes.

Up to $430K
2028-03-14
health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Sensory Entrained Transcranial Magnetic Brain Stimulation (seTMS) for Major Depression

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NIH

This is a Veteran’s Administration Career Development Award 2 proposal for Jessica M. Ross, Ph.D. entitled “Sensory Entrained Transcranial Magnetic Brain Stimulation (seTMS) for Major Depression.” The goal of this project is to study phase-aligned TMS (i.e. brain wave synchronized TMS) in Veterans, to enhance personalized neuromodulation and clinical outcome for the 60-80% currently not achieving remission while not increasing cost and burden. To bring phase-aligned TMS to Veterans, the PI developed Sensory Entrained TMS (seTMS), a clinic-ready augmentation therapy. The seTMS protocol uses music to synchronize brain waves during TMS, to deliver precisely-timed TMS when the brain is maximally excitable. seTMS operates within the guidelines of currently FDA-cleared protocols, does not require EEG or phase estimation algorithms, and is affordable and accessible because it only requires headphones and plug-and-play software that is compatible with existing equipment. This work will be a thorough investigation of seTMS for effective VA clinical use. The current study aims to 1) apply pulses of seTMS to the dlPFC in Veterans and compare brain changes (target engagement in electroencephalography, EEG) to those from standard pulses of TMS; 2) apply seTMS to the dlPFC in Veterans with depression and compare target engagement to those from standard pulses of TMS; 3) treat MDD with an accelerated form of seTMS (se-aTBS) or standard a-TBS to compare symptom reduction and long-term target engagement (lasting brain changes). Symptoms will be measured using standard clinical scales, administered during the first visit (Day 0), during the last visit following TMS, and at 1-month post-treatment. These scales are the Montgomery-Åsberg Depression Rating Scale (primary) and Columbia Suicide Severity Rating Scale (secondary), and the standard scales collected routinely in the Palo Alto MIRECC Precision Neuromodulation Clinic: Patient Health Questionnaire (PHQ-9), the Brief Symptom Inventory 18 (BSI-18), PTSD Checklist for DSM-5 (PCL-5), Beck Scale for Suicidal Ideation (BSSI), Generalized Anxiety Disorder 7-item (GAD-7), and the 36-Item Short Form Survey (SF-36) Health Survey. The PHQ-9 and GAD-7 will also be given to the Veterans on each day of treatment (Days 1-4) after the last protocol of the day. Perceptual ratings of scalp feeling and pain will also be recorded to assess tolerability and feasibility in Veterans. The overarching research hypothesis is that seTMS will enhance prefrontal circuit changes in non-depressed and depressed Veterans and improve clinical outcomes when used for treating Major Depression (MDD) while being feasible for clinical use. The specific hypotheses are that 1) seTMS will enhance TMS-induced brain changes in Veterans and 2) Veterans with MDD and 3) the se-aTBS treatment protocol will lead to greater reduction of clinical symptoms than standard aTBS, and be feasible and tolerable, in Veterans with MDD. This CDA-2 award would allow Dr. Ross to gain proficiency in 1) theory and models of brain plasticity in Veteran clinical populations, 2) traditional and innovative clinical design, 3) adaptive and personalized TMS methodologies, and 4) professional development for a career at the VA. Training and research for the project will be conducted at both the VA Palo Alto Health Care System (VAPAHCS) as part of the Mental Illness Research, Education and Clinical Center (MIRECC) and Stanford University School of Medicine, in the Department of Psychiatry and Behavioral Sciences. Both sites offer excellent intellectual and physical resources to complete the proposed work. SeTMS is a novel intervention that harnesses principles of sensorimotor neuroscience and has the potential to increase the efficacy of FDA-cleared TMS protocols without increasing cost for Veterans with Depression.

2030-12-31
health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Sex and Age Informed Profiles of Executive Function in Autism Across Development

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NIMH - National Institute of Mental Health

PROJECT SUMMARY Challenges in executive functioning (EF) are highly prevalent in autism; however, profiles of EF vary greatly. Challenges in both “cool,” logical skills, such as working memory and planning, and “hot,” state-dependent skills, such as inhibition and emotional regulation, have been implicated. For both non-autistic and autistic individuals, EF predicts a myriad of key functional outcomes including adaptive behavior, academic success, and mental health. There is burgeoning evidence that EF serves as an underlying mechanism for the development and maintenance of mental health outcomes as well as the heterogeneity inherent to autism. Mental health and EF represent (1) two key drivers of quality of life in autism, (2) are endorsed by autistic people as a high priority for research and intervention, and (3) are tangible and frequent targets of personalized intervention approaches. As such, understanding distinct profiles of EF, the developmental course of EF, and how EF challenges vary as a function of key variables such as sex and age is a promising step towards individualized, actionable intervention across the lifespan. Data driven approaches have been promoted in autism to understand heterogeneity across constellations of traits, yet extant work has not been sufficiently powered to examine the unique and intersecting impact of sex, age of diagnosis, and chronological age on EF. The proposed project will adopt a data driven approach (Latent Profile Analysis–LPA) to parse the heterogeneity of EF across development (4 to 25 years), spanning critical developmental periods where EF development is rapid. In Aim 1, we will use multi-group LPA to identify profiles of EF in a large sample (N = 724) of autistic and non-autistic individuals, equally split on sex and diagnosis. Profile modeling will be based on 5 subscales from a caregiver-reported EF measure (Behavior Rating Inventory of Executive Functioning). In Aim 2, we will determine how profiles of EF vary as a function of age, sex, and age of diagnosis in our autistic cohort. In Aim 3, we will conduct exploratory analysis to examine how EF profiles predict internalizing behaviors in both cohorts. We hypothesize 3 profiles will emerge in each cohort, with the following profiles in the autistic cohort: (A) challenges across all EF domains, (B) challenges in shifting, working memory, and planning, and (C) challenges in emotional regulation and inhibition. We anticipate our variables of interest, including age, sex, and age of diagnosis, will differentially predict profile membership in line with existing literature. Identifying these profiles can (1) inform educational and therapeutic approaches, (2) promote autonomy and well-being for autistic individuals, and (3) elucidate the mechanisms by which EF challenges contribute to mental health across key developmental windows. Training aims include advancing Ms. Russell’s understanding of EF and its relationship to clinical outcomes, enhancing her statistical skills by training in data-driven approaches, and expanding her experience working with data from autistic adults. These aims will support Ms. Russell establishing herself as an expert within the field of autism phenotyping.

Up to $42K
2029-06-30
health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

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