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Functional Neurological Disorders (FNDs) are characterized by symptoms of altered voluntary motor or sensory function with clinical findings providing evidence of incompatibility between the symptoms and recognized neurological or medical conditions. FNDs are highly prevalent and associated with significant morbidity, health care costs, and even mortality. In some respects, this group of conditions sits at the intersection of neurology and psychiatry, but the majority of cases first come to the attention of neurologists. Management is complex and requires interdisciplinary approaches. Given the disability caused by the symptoms, and the high cost in healthcare utilization and loss of productivity, FNDs amount to a significant missed opportunity for therapeutic intervention and therefore, a healthcare crisis. Diagnosis and management of FNDs remain very challenging. Diagnostic criteria have been proposed but they are not universally agreed upon. Diagnosis is based on positive clinical findings, and can be supported by laboratory or ancillary investigation findings. Certain FND subtypes are more difficult to correctly diagnose than others. More importantly, laboratory-supported diagnosis is possible, and biomarkers can be developed, but significantly more research is needed in these areas to advance clinical management of FNDs. Therapies exist and have been studied in select populations but gathering high-level evidence through clinical trials is hampered by limitations in available outcome measures. Differential responses to treatments have been recorded, and thus, prediction of aggregate treatment response has been difficult. This FOA invites researchers to submit prospective clinical projects that address critical needs for clinical trial readiness in FNDs. Projects appropriate for this FOA include the validation of biomarkers, endpoints and clinical outcome assessments (COA) that are fit-for-purpose and have a defined context of use for clinical trials.

The NIH Research Education Program (R25) supports research education activities in the mission areas of the NIH. The over-arching goal of this NIH Blueprint for Neuroscience Research R25 program is to support educational activities that complement and/or enhance the training of a workforce to meet the nations biomedical, behavioral and clinical research needs. To accomplish the stated over-arching goal, this FOA will support creative educational activities with a primary focus on Courses for Skills Development. This FOA solicits Research Education Grant (R25) applications to develop and implement short courses on neurotherapeutics development for academic neuroscientists. The short courses should provide participants with a sufficient overview of the neurotherapeutics development process to (1) understand the steps required for therapeutics development, (2) anticipate and overcome common challenges in the process, and (3) interact effectively with collaborators who have expertise in various aspects of therapeutics development. The short courses should primarily target independent academic neuroscience researchers and senior post-doctoral fellows interested in incorporating treatment development into their research programs.

The purpose of this Notice is to inform potential applicants an area of special interest to NHLBI, NINDS and NIA in research to understand mechanisms of vascular contributions to cognitive impairment and dementia (VCID) and to develop new approaches for the treatment of VCID.

There is consensus that environmental toxicants are a risk factor for AD/ADRD, but causality has been largely elusive. While human studies demonstrating an association of AD/ADRD with toxicant exposures are relatively abundant, there is a clear unmet need for more mechanistic research to support or refute the clinical relevance and the biological plausibility of an impact on disease initiation, progression, or modification. This is especially important for understanding the potentially modifiable causes of racial and socioeconomic inequities. The RFA will encourage neuroscientists to conduct mechanistic AD/ADRD research on the actions of neurotoxicants on the nervous system. The scope of research includes but is not limited to in silico modeling, in vitro assay development to correlate chemical exposure to AD/ADRD biology, and in vivo studies on the modification of known AD/ADRD targets by neurotoxicants of concern, and conversely, whether known targets for these neurotoxins play a role in the etiology of AD/ADRD. The development and validation of neuropathological, neurophysiological, and neurobehavioral animal models that simulate potential toxicant exposures in humans would be one goal, and when possible, these studies will include comparisons of exposures across the lifespan.

The purpose of this Funding Opportunity Announcement (FOA) is to solicit applications to accelerate development, testing and implementation of evidence-based interventionsthat are culturally and linguistically appropriate for NIH-designated health disparity populations[1] (HDPs)to mitigate disparities in provision of care and treatment decisions, reduce susceptibility to chronic pain and improve patient outcomes. Applications are encouraged for studies that utilize evidence-based strategies that mitigate: 1) the effects of bias, stigma and discrimination at multiple levels, and 2) socioeconomic, environmental and other barriers to quality pain assessment, treatment and management are desired outcomes of this initiative. Strategies to increase successful HDP patient engagement and bolster inclusion to enhance better pain management outcomes are also desired.

This funding opportunity announcement (FOA) invites research projects that seek to explain the underlying mechanisms, processes, and trajectories of social relationships and how these factors affect outcomes in human health, illness, recovery, and overall wellbeing. Types of projects submitted under this FOA include studies that prospectively assign human participants to conditions (i.e., experimentally manipulate independent variables) and that assess biomedical and/or behavioral outcomes in humans to understand fundamental aspects of phenomena related to social connectedness and isolatedness. NIH considers such studies as prospective basic science studies involving human participants that meet the NIH definition of basic research and fall within the NIH definition of clinical trials (see, e.g., NOT-OD-19-024) Types of studies that should submit under this FOA include studies that prospectively assign human participants to conditions (i.e., experimentally manipulate independent variables) and that assess biomedical or behavioral outcomes in humans for the purpose of understanding the fundamental aspects of phenomena without specific application towards processes or products in mind. Applications proposing studies that include but not limited to model animal research or observational studies involving humans should submit under the companion Clinical Trials Not Allowed version of this FOA.

This funding opportunity announcement (FOA) invites research projects that seek to model the underlying mechanisms, processes, and trajectories of social relationships and how these factors affect outcomes in health, illness, recovery, and overall wellbeing. Both animal and human subjects research projects are welcome. Researchers proposing basic science experimental studies involving human participants should consider the companion FOA TEMP-14931 "Research on Biopsychosocial Factors of Social Connectedness and Isolation on Health, Wellbeing, Illness, and Recovery (R01 Basic Experimental Studies with Humans Required)".

The purpose of this funding opportunity announcement (FOA) is to invite applications to continue support of a national program of mentored research career development for junior neurosurgeon faculty at institutions nationwide that support neurosurgical research. The goal of the program is to expand the cadre of neurosurgeon investigators trained to conduct research into neurological disorders, making use of their neurosurgical training.

NINDS is issuing this Notice of Special Interest to encourage the submission of applications focused on the development and validation of biomarkers for functional neurological disorders (FND). FND are a complex and heterogeneous group of neuropsychiatric syndromes. They are characterized by symptoms of altered voluntary motor or sensory function and frequently have comorbid medical, neurological, and psychiatric disorders. Although patients with FND represent the second commonest category of referrals to neurology outpatient clinics after headache, management is complex and requires interdisciplinary approaches. The high prevalence of FND, the disability caused by symptoms, high cost in healthcare utilization and loss of productivity points to an important opportunity for development of effective therapeutic interventions. This common, disabling, and costly group of conditions sits at the intersection of neurology and psychiatry. In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) the term functional is used as the primary descriptor in the term for this group of conditions, although the term conversion disorder is still accepted as an alternative expression that acknowledges unconscious processes in patients, though it emphasizes the implicit inference of causative psychological stressors, which are not always present or may not be readily identifiable. Diagnostic criteria for FND have been proposed, but are not universally accepted, and have varying rates of interrater reliability, depending on the symptom presentation (high for non-epileptic psychogenic seizures; poor for other FND). For this reason, diagnosis remains very challenging. Recent recommendations suggest that diagnosis should be based on positive clinical findings and supported, when necessary, by laboratory or ancillary investigation findings. Certain FND subtypes are more difficult to correctly diagnose than others.

The neurovascular unit involves multiple pathways that contribute to neurodegeneration. Astrocytes, due to their overlapping roles regulating the blood brain barrier, neuronal health and response to degenerating cells, are uniquely positioned to be therapeutic targets. Astrocytes are a fundamental component of the neurovascular unit and are known to play a role in regulating the blood brain barrier and APOE signaling. However, the mechanistic role of astrocytes for the neurovascular unit in health and disease, including in vascular contributions to cognitive impairment and dementia (VCID) and across the spectrum of AD/ADRD diagnoses, is largely unknown, and represents a gap area and an opportunity for research investment. This initiative would represent the first targeted initiative on the fundamental role of astrocytes in AD/ADRD at the NIH.