Funded Research Projects

Permanent URI for this collectionhttps://hdl.handle.net/20.500.14641/189

An index of publicly funded research projects conducted by Texas A&M affiliated researchers.

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Now showing 1 - 20 of 494

Neural Substrates of Contextual Memory in Fear Extinction
Psychology; https://hdl.handle.net/20.500.14641/1089; DHHS-NIH-National Institute of Mental Health
PROJECT SUMMARY Therapeutic interventions, such as exposure therapy, reduce pathological fear in patients with anxiety disorders. Extinction is a fundamental form of learning that underlies these therapies. A major challenge to extinction-based therapies is that the fear reduction is often transient and bound to the place or context in which therapy occurs. For example, when patients confront phobic objects or reminders of trauma outside of the clinic, their fear often relapses. This reveals that extinction learning does not erase fear memory, but yields a context-dependent “safety” memory that inhibits the expression of fear in the place where it is learned. Accordingly, the long-term goal of this project is to understand the neural substrates of fear extinction and relapse, particularly the specific brain circuits involved in the contextual control of extinction. Work in the current funding period of this project has focused on renewal, a relapse of extinguished fear outside the extinction context. Importantly, it was found that the hippocampus (HPC) mediates renewal by inhibiting retrieval of extinction memories encoded by the infralimbic (IL) cortex. In the extinction context, the suppression of conditioned fear is thought to involve IL inhibition of amygdala neurons encoding fear memory. However, recent data challenge this notion—silencing prefrontal-amygdala projections does not impair extinction retrieval. Hence, the precise mechanism for suppressing fear after extinction is still unknown. Recent work on this project suggests a novel alternative: the mPFC may suppress the reactivation of hippocampus-dependent fear memories to facilitate context-dependent extinction memory retrieval. The mPFC projects to the HPC via the thalamic nucleus reuniens (RE), and RE inactivation or chemogenetic silencing of mPFCgRE projections impairs the expression of extinction. Based on this work, it is hypothesized that the RE mediates mPFC-HPC interactions required for context-dependent retrieval of extinction memories. This hypothesis will be tested in three specific aims. The first aim explores whether the mPFC, particularly IL, suppresses the retrieval of extinguished fear memories via RE projections to the HPC. The second aim examines whether the activity of HPC ensembles representing fear and extinction memories are regulated by the RE. The third aim determines whether the RE coordinates oscillatory synchrony in HPC and mPFC during extinction retrieval. The proposed work will elucidate the specific neural circuits mediating the expression of extinction and has important clinical implications for developing therapeutic interventions that target these neural circuits to promote fear suppression and oppose relapse.
Neural Circuits for Stress-Impaired Extinction Learning
Psychology; https://hdl.handle.net/20.500.14641/1089; DHHS-NIH-National Institute of Mental Health
Project Summary Clinical disorders of fear and anxiety, including trauma- and stressor-related disorders, represent an enormous public health burden. Cognitive-behavioral therapies, such as prolonged exposure therapy, have proven to be remarkably effective in reducing pathological fear in patients with these disorders. Nonetheless, there are a number of factors that limit the efficacy of exposure therapy. In particular, stress undermines exposure-based therapies by impairing extinction learning and promoting fear relapse. Despite years of work elucidating the neural circuitry for extinction, the neural mechanisms responsible for stress-induced extinction impairments remain poorly understood. One possibility is that stress dysregulates neuronal activity in the medial prefrontal cortex (mPFC), a brain area that is critical for extinction learning. In support of this possibility, we have recently shown that footshock stress causes lasting decreases in the spontaneous firing of neurons in the infralimbic (IL) division of the mPFC in rats. Decreases in IL firing were associated with an “immediate extinction deficit” (IED), an extinction impairment that occurs when extinction is performed soon after fear conditioning (a stressor). Importantly, systemic administration of propranolol, a ß-noradrenergic receptor antagonist, prevented both the stress-induced depression of IL firing and the IED, suggesting a role for locus coeruleus norepinephrine (LC-NE) in this phenomenon. Although these data reveal that noradrenergic transmission is involved in the stress-induced depression of mPFC firing, the neural circuit by which stress perturbs mPFC firing is unknown. Interestingly, we have found that propranolol rescues the IED when delivered to the basolateral amygdala (BLA), but not the IL. Based on this work, we propose a novel hypothesis that stress-induced NE release from the LC recruits an inhibitory BLA->IL circuit that dampens activity in IL principal neurons to impair the acquisition and retention of long-term extinction memories. We propose three specific aims to test this hypothesis using a combination of in vivo electrophysiology, functional circuit tracing, and pharmacogenetic manipulations (e.g., `designer receptors exclusively activated by designer drugs' or DREADDs). The first specific aim of the project examines whether LC-NE projections to the IL or BLA are necessary and sufficient for stress-induced changes in mPFC firing and extinction learning deficits. The second specific aim examines explores whether BLA neurons projecting to the IL or PL mediate these effects. The third specific aim determines whether parvalbumin interneurons (PV-INs) in the mPFC are recruited by LC- NE activation and mediate the immediate extinction deficit through feed forward inhibition by BLA afferents. The outcomes of these aims will advance a novel circuit mechanism for stress-induced extinction impairments. Understanding this mechanism will facilitate the development of novel pharmacotherapeutic approaches that optimally engage mPFC circuits to facilitate extinction learning under stress.
Exploring Striatal Circuits Underlying Behavioral Flexibility During Punishment of Cocaine Seeking
Psychology; https://hdl.handle.net/20.500.14641/1103; DHHS-NIH-National Institute of Neurological Disorders and Stroke
Abstract A hallmark of drug addiction is the uncontrollable urge to seek drug despite negative consequences— drug seeking individuals become resistant to punishment. Punishment resistance has also been observed in an animal model of addiction. In this model, some rats continue to seek cocaine despite a footshock outcome (i.e., punishment), whereas other rats instead reduce their cocaine seeking to avoid footshock. The propensity to reduce cocaine seeking to avoid a negative consequence may require behavioral flexibility, an adaptive form of learning that allows changes in behavior in response to new features in the environment. Previous work using measures of behavioral flexibility, such as reversal learning and strategy shifting, have shown that striatal circuits are essential for expressing behavioral flexibility. Specifically, frontal cortex areas such as the orbitofrontal cortex (OFC) and thalamic areas such as the parafascicular thalamus (PF) target the dorsal striatum (DS) and help track events in the environment that are important for updating behavior. One striatal cell type that is important for the role of PF and OFC in behavioral flexibility are cholinergic interneurons (CIN). However, the role of be- havioral flexibility and its neural substrates in punishment resistance is poorly understood. The proposed work will test the hypothesis that punishment-resistant cocaine seeking results from reduced behavioral flexibility when faced with negative consequences. Specific Aim 1 (F99, dissertation phase) will identify a DS CIN mechanism that supports behavioral flexibility during punishment of cocaine seeking in rats, using immunohistochemistry, behavioral pharmacological, and optogenetics. Specific Aim 2 (K00, postdoctoral phase) proposes a research direction that will focus on the role of OFC in driving vs suppressing punishment-resistant cocaine seeking, which serves as an extension of the dissertation work that will be completed in Aim 1. I will acquire technical skills related to a measure of neurotransmission, such as in vivo calcium imaging, to fully investigate OFC activity patterns related to cocaine seeking in the face of negative outcomes. In addition, Aim 2 describes the qualities I will seek in a postdoctoral mentor and research environment that can support my research interests, technical training goals, and growth as an independent neuroscientist. Overall, the proposed research in this training fel- lowship aims to define the neural mechanisms underlying reduced behavioral flexibility, which will contribute to identifying targeted treatment strategies for drug addiction.
Novel Water-Soluble Adjunct Anticonvulsants for Nerve Agents
Neuroscience And Experimental Therapeuti; https://hdl.handle.net/20.500.14641/1098; DHHS-NIH-National Institute of Neurological Disorders and Stroke
Project Summary The overall goal of this proposal is to identify novel ‘water-soluble’ neurosteroid anticonvulsants that will control benzodiazepine-resistant seizures and brain injury caused by acute organophosphate (OP) intoxication. Exposure to nerve agents or OP compounds can result in persistent seizures, status epilepticus (SE), and permanent brain injury. Benzodiazepine anticonvulsants are the primary therapy for OP-induced SE but they do not sufficiently protect the brain from SE at later time after exposure. Neurosteroids are robust anticonvulsants against SE induced by a variety of OP agents and hence they can overcome key limitations of benzodiazepines. The objective of this project is to investigate the efficacy and pilot safety of new water-soluble synthetic analogs of brexanolone (FDA-approved) as adjunct anticonvulsants to midazolam therapy for OP intoxication. Test drugs are administered as adjunctive treatment either with midazolam or after midazolam has failed to control SE. The goal is to rapidly stop seizures, reducing the further brain damage. This novel therapy is based on the molecular mechanisms of neurosteroids and cellular changes involved in refractory SE caused by OP agents. The proposed adjunct therapy is based on central hypothesis that synthetic neurosteroids that enhance phasic and extrasynaptic tonic inhibition more effectively control nerve agent-induced SE and neuronal damage than benzodiazepines alone and thereby completely mitigate morbidity. The neurosteroid brexanolone is highly effective for controlling OP-induced SE and neuronal damage in rat models, but has certain limitations for its launch as medical countermeasure. Valaxanolone and lysaxanolone are two lead hydrophilic analogs of the neurosteroid with improved biopharmaceutical and pharmacological (extrasynaptic-preferring) properties. Test drugs can be formulated as dry powder for injection for extended stability and they have promising efficacy as medical countermeasures for OP-induced SE. The key emphasis is to generate requisite data on the efficacy and safety profile of lead candidates and identify at least one lead drug for further development. The proposed goals will be implemented by addressing three specific aims: (Aim 1) To determine the adjunct efficacy of hydrophilic neurosteroid analogs against DFP-induced SE and brain damage; (Aim 2) To determine the adjunct efficacy of hydrophilic neurosteroid analogs against Soman-induced SE and brain damage; and (Aim 3) To determine the preclinical pharmacokinetics and pilot safety of lead drugs. The project will be implemented as per the progressive “go/no-go” milestones plan focusing on three primary outcome measures: (i) anticonvulsant efficacy; (ii) neuroprotectant efficacy; and (iii) prevention of neurodegeneration and behavior dysfunction. The outcome from this project will identify a novel adjunct anticonvulsant to midazolam for OP intoxication and that the “dry-power for injection” system would provide a lengthy shelf-life for stockpiling at the military and civilian centers. Thus, such neurosteroid-midazolam combination will be highly efficient investment for the biodefense program.
Components of Selection History and the Control of Attention
Psychology; https://hdl.handle.net/20.500.14641/1074; DHHS-NIH-National Institute On Drug Abuse
PROJECT SUMMARY/ABSTRACT Attention selects which aspects of sensory input receive cognitive processing and thereby influence behavior. Drug addiction alters the attentional system, resulting in prominent attentional biases towards drug cues. Such drug-related attentional biases are related to the broader phenomenology of addiction, including craving and relapse. There has been long-standing interest in implementing attentional bias measures in clinical settings, either as a predictive measure to inform treatment decisions or as a target of treatment. However, a major barrier to the realization of this goal is that current means of assessing these biases are not sufficiently precise to support clinical utility, which has stifled progress in this area. Mirroring this complexity, and underscoring the need for clarity, debate has arisen concerning the role of learning history in the guidance of attention more broadly. Persistent attentional biases have been linked to reward history, learning from aversive outcomes, and outcome-independent selection history (e.g., familiarity). Emerging accounts of such experience-dependent attentional biases disagree about the nature of the underlying mechanism(s) involved. If we do not understand the variety of influences of learning history on attention at a fundamental level, how can we understand how these influences contribute to addiction-related attentional biases? The proposed research directly addresses this need by identifying, isolating, and measuring multiple hypothesized components of the attentional biases that characterize addiction, providing the precision necessary for more accurate predictions of patient outcomes and more targeted efforts to improve these outcomes through attentional bias modification. Specific Aim 1 will distinguish between common and distinct attentional priority signals arising from reward learning and reward-independent selection history, probing both the cognitive and neural mechanisms underlying each of these sources of priority. Specific Aim 2 will identify the cognitive profile and neural mechanisms underlying attentional biases attributable to aversive conditioning, which together with Specific Aim 1 will provide a comprehensive picture of the multifaceted nature of experience-dependent attention. The overarching goal of the proposed research is to characterize multiple distinct components of experience-dependent attentional bias that contribute to attentional biases evident in drug-dependent individuals. These fundamental components of attentional bias will provide a much more precise window into the attentional processes that are relevant to our understanding of addiction than existing measures can offer. It is anticipated that the knowledge gained from the proposed research with provide a foundation for overcoming fundamental limitations in the clinical utility of attentional bias measures, allowing for fruitful exploration of this aspect of addiction in the context of improving assessment and treatment.
A Digital-Twin Enabled Testbed for Public Safety Communication Technologies
Department Of Visualization; https://hdl.handle.net/20.500.14641/1105; DOC-National Institute of Standards and Technology
This project will build a digital-twin enabled testbed with the state of the art user interface/user experience technologies and advanced simulation models to provide a photorealistic virtual reality environment for first responders and emergency managers to engage, experience, and explore the latest sensing and communication technologies. At the center of this project is a digital twin created for the training sites in the Disaster City®, a 52-acre training facility managed by the Texas A&M Engineering Extension Service (TEEX) to deliver the full array of skills and techniques needed by today’s emergency response professionals. In addition to serving as a virtual testing and training facility for first responders, the testbed can also function as an open platform for researchers and entrepreneurs worldwide to collaborate with first responders and emergency managers to develop next-generation sensing and communication technologies and devices specialized for public safety usage. We envision the proposed testbed as an attempt towards a systematic plan to fill critical technology gaps identified by stakeholders and to build a public-safety-focused R&D ecosystem with a long-lasting impact.
Research Project w/Choi: AI-Based Roadway Flooding Digital Twinning (AIR-FLOOD)
Construction Science; https://hdl.handle.net/20.500.14641/1068; DOC-National Oceanic and Atmospheric Administration
TBD
The Predictability of Oxygen and Its Metabolic Consequences for Fisheries on Decadal Time Scales
Oceanography; https://hdl.handle.net/20.500.14641/1114; DOC-National Oceanic and Atmospheric Administration
TBD
MERHAB19: Implementing Karenia brevis Respiratory Risk Forecast System in the Gulf of Mexico
Oceanography; https://hdl.handle.net/20.500.14641/1082; DOC-National Oceanic and Atmospheric Administration
TBD
Incorporating Fish in Earth System Predictions
Oceanography; https://hdl.handle.net/20.500.14641/1114; DOC-National Oceanic and Atmospheric Administration
TBD
Treatment Intensity Factors Related to Efficient and Effective Communication Intervention for Individuals with ASD and Complex Communication Needs
Educational Psychology; https://hdl.handle.net/20.500.14641/1077; Department of Education
Individuals with autism spectrum disorder (ASD), mod.-severe intellectual delay (ID) and complex communication needs (CCNs) typically require highly intensive, costly, individualized educational interventions; thus, this project will lead to the development of protocols for instructional personnel and parents to guide them in selecting treatment intensity parameters and implementing efficient, acceptable, and effective treatment for improving communication the target population. We will conduct a meta-analysis to investigate differential effects of treatment intensity parameters (i.e., dosage, generalization, treatment integrity) and related mediators and moderators of communication acquisition in a range of vocal, unaided and aided manualized, and replicable intervention strategies. We will investigate the quality of the designs based on What Works Clearinghouse. Our meta-analysis will focus on (a) the degree to which dosage parameters (using Warren, Fey & Yoder, 2007) are utilized, (b) which parameters are most often reported, (c) interactions between learner characteristics and dosage parameters, and (d) distinctions in dosage parameters between social pragmatic communication intervention protocols compared to functional- behavioral protocols (e.g., descriptively examining dosage patterns within specific manualized programs) and other popular manualized programs.
The miR15a/16 Axis and Precision Gene Intervention to Provide a Novel Therapy for Lung Cancer
Kinesiology & Sport Management; https://hdl.handle.net/20.500.14641/1075; DOD-Army-Medical Research and Materiel Command
TBD
Inborn Errors of Innate Immunity and Impaired Anti-microbial Defenses in Primary Mitochondrial Diseases
Microbial Pathogenesis And Immunology; https://hdl.handle.net/20.500.14641/1067; DOD-Army-Medical Research and Materiel Command
TBD
LucRNA Regulation of Intracellular Parasitism by Bacterial Biothreat Agents
Microbial Pathogenesis And Immunology; https://hdl.handle.net/20.500.14641/1101; DOD-Navy-Office of Naval Research
TBD
Coral Reef Ocean Acidification Sentinel Site in the Flower Garden Banks National Marine Sanctuary: Data Collection and Analysis
Oceanography; https://hdl.handle.net/20.500.14641/1102; DOI-Bureau of Ocean Energy Management
TBD
CESU: Historic Canoe Conservation Project at Everglades National Park
Anthropology; https://hdl.handle.net/20.500.14641/245; DOI-National Park Service
The purpose of this undertaking is to: Assist a team lead by cultural representatives of the National Park Service, Southeast Archaeological Center with 1), the recovery of the ~23-foot dugout canoe discovered off Hog Key, Ten Thousand Islands District, Everglades National Park, 2), the packaging and transportation of the canoe to the Conservation Research Laboratory at Texas A&M University, 3) the stabilization the artifact and, 4), to provide assistance with the fabrication of a display cradle and its installation at the NPS Visitor Center.
CESU- Documentation of Slave Buildings at Natchez National Historical Park
Department Of Architecture; https://hdl.handle.net/20.500.14641/1109; DOI-National Park Service
In cooperation with Center for Heritage Conservation at Texas A&M University, this project will record and fully document one dozen buildings associated with the enslaved at two NATC sites prior to the Civil War, providing insight into their experiences and lifeways. Through its enabling legislation, Natchez National Historical Park (NATC) is charged with interpreting the world of chattel slavery. In order to fulfill its mission, NATC and its partners are undertaking a historic building survey of the slave dwellings and other outbuildings at two NATC sites, Melrose and the William Johnson House. This project will advance NATC’s mission and public interpretation of its historic sites.
The Effectiveness of Scenario-based Micro-learning Interactive Videos
Veterinary Integrative Biosciences; https://hdl.handle.net/20.500.14641/1099; DOJ-National Institute of Corrections (NIC)
The goal of this program is to assist federal, state, local, and tribal correctional agencies by creating and offering scenario-based microlearning interactive videos that can assist in reinforcing correctional excellence. These videos will be added to NIC’s growing library of on-demand training content. Since the safety of inmates, staff, the public, and the orderly operation of correctional agencies is critical for successful outcomes, the need for training that reinforces professionalism and excellence in some of the primary correctional duties exists. The audience includes nearly 400,00 correctional officers from agencies across the United States.
Training and Educational Materials Development - SHTG-FY-23-02
Construction Science; https://hdl.handle.net/20.500.14641/1091; DOL-Occupational Safety and Health Administration
TAMU non-profit proposes to develop on-site autonomous machine training materials for employers and workers in the construction industry. The targeted audience includes all construction employers and workers, new and experienced, that perform tasks with or close to on-site autonomous machines in the construction industry. The training topics that will be covered in this proposed project include types of on-site autonomous machines and applications in the construction industry, potential hazards associated with these machines, accident root causes, typical safety and health outcomes, risk mitigation strategies, and processes for applying safety controls and best practices. At the end of the project, downloadable versions of training materials such as PowerPoint presentations, course outlines, handouts, sign-in sheets, pre-and post-tests evaluations, and instructor and student manuals will be provided. In addition, the materials created through this effort will be tested during a pilot training for 50 workers and employers pilot tested in English and Spanish.
Searching for Inverse Compton Emission from Globular Clusters with Fermi-Lat and HAWC
Physics And Astronomy; https://hdl.handle.net/20.500.14641/1104; NASA-Shared Services Center
TBD

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