# NINDS 2023 Congressional Budget Justification

## Director's Overview

The mission of the National Institute of Neurological Disorders and Stroke (NINDS) is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease for all people.  Common and rare neurological disorders affect people across all ages and population groups, with enormous public health impact.  Despite the complexity of the human nervous system and its limited capacity for repair, research funded and conducted by NINDS is improving diagnosis, treatment, and prevention for many neurological disorders.  And, armed with the power of big data and increasingly sophisticated tools and methods, basic research on the nervous system and mechanisms of disease is yielding exciting opportunities for future progress.  A new NINDS Strategic Plan will guide the institute for the next five years in advancing neuroscience research; strengthening research training and workforce diversity; enhancing communication and engagement with researchers, patients, and the public; and fostering positive workforce culture.  This plan reflects priorities for NINDS in the face of major changes affecting medical research and society at large.

### COVID-19 and the nervous system: past investments set the stage

As the coronavirus disease-19 (COVID-19) pandemic unfolded, accounts began to describe neurological symptoms associated with SARS-CoV-2 infection.  While most people infected with the virus have mild, moderate, or no neurological symptoms, some people experience symptoms including muscle aches, headaches, dizziness, and altered taste and smell.  COVID-19 also causes blood cells to clump and form clots in arteries and veins throughout the body, which can cause stroke.  Other less common but severe effects can include delirium, seizures, muscle weakness, nerve injury, pain syndromes, and rare inflammatory conditions.

Extensive experience investigating the effects of other viral infections on the nervous system allowed researchers to pivot quickly to studying COVID-19.  NINDS intramural investigators have been leaders in this research and reported early evidence of leaky blood vessels in the brain associated with inflammation and damage.  NINDS also supported supplements to research grants to allow extramural investigators to shift their focus to COVID-19.  By leveraging infrastructure in place for the NIH Helping to End Addiction Long-term (HEALSM) Initiative, NINDS established the COVID-19 Neuro Databank/Biobank database to collect information on COVID-19-related neurological symptoms and outcomes, as well as biospecimens for further research.  Additional projects focus on brain pathology, disorders of consciousness, seizures, stroke delirium, biomarkers of brain damage, and other neurological complications.  Also, NINDS clinical networks have provided study sites and infrastructure for clinical trials within the NIH Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) program.

Beyond acute effects of COVID-19, some people have persistent, disabling symptoms that last for weeks or months (referred to as long COVID), including neurological symptoms such as pain, headaches, fatigue, postural orthostatic tachycardia, sleep disorders, post exertional malaise, and cognitive difficulties.  Along with the National Heart, Lung, and Blood Institute (NHLBI), NINDS is a leading partner in the NIH REsearching COVID to Enhance Recovery (RECOVER) Initiative, established to learn why some people have prolonged symptoms or develop new or returning symptoms after SARS-CoV-2 infection, which will inform ways to prevent long COVID and help people recover.  Findings may also shed light on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a poorly understood disorder with no effective treatments.  Many people with ME/CFS report its onset after an infectious-like illness, and some symptoms associated with long COVID overlap with those of ME/CFS. 

NINDS and NIH investments in COVID research are yielding results.  Studies suggest that neurological symptoms of COVID-19 result primarily from the virus’s effects on brain blood vessels and the body’s immune response to infection rather than direct viral infection of the brain or nervous system.  Still, many questions remain about how SARS-CoV-2 affects the brain and other organs, and more attention is needed to understand the impact of the virus and the pandemic for chronic neurological diseases, including Alzheimer’s and Alzheimer’s Disease Related Dementias (AD/ADRD).  Given the large and still rising number of Americans who have had COVID-19, research to understand and limit acute and long-term nervous system effects remains a critical priority. 

### Unrelenting needs and promising opportunities

The COVID-19 pandemic exacerbated the crisis of opioid misuse, addiction, and overdose.  Drug overdose deaths rose nearly 30 percent in 2020, with 75 percent of those deaths linked to opioids,1 and poorly treated or unmanaged pain increased alongside changes to health care and support systems necessitated by the pandemic.  NINDS leadership in research to develop non-addictive therapies for pain is a key pillar to addressing this crisis and a major part of the NIHHEAL InitiativeSM.  Building on basic research to understand acute and chronic pain, HEAL programs are advancing promising pain therapies, including a new non-opioid medication for neuropathic pain and implanted devices and noninvasive brain or nerve stimulation for managing pain.  HEAL investigators have also patented novel targets for inflammatory pain, migraine, and visceral pain; and the Early Phase Pain Investigation Clinical Network (EPPIC-Net), led by NINDS for the HEAL InitiativeSM, is testing a treatment for knee osteoarthrosis pain.

Treatments for other common and rare neurological disorders continue to be pressing needs, and again, research is providing avenues for progress.  Despite decades of declining stroke death rates, almost 800,000 people in the United States suffer strokes each year, with about 150,000 deaths and many others left with major disabilities.2 Recent improvements in emergency stroke treatment expand the time window for effective intervention and present opportunities for developing adjunct therapies that protect the brain.  As the population ages, dementia is a large and growing public health burden.  Yet, again, research points to opportunity.  Evidence suggests that managing stroke risk factors may also prevent dementia, and increased investment in AD/ADRD research is growing understanding of disease mechanisms, with hope for treatments to prevent or slow neurodegeneration.  For about a third of people with epilepsy, existing therapies are ineffective, and the prevention of epilepsy remains elusive.  NINDS has contributed to new anti-seizure medicines with improved side-effect profiles, and current programs focus on drug resistant epilepsy and epilepsy prevention.  Finally, causal gene mutations are known for hundreds of rare genetic neurological disorders, many of which affect infants and children, but the small number of people with each condition makes research difficult and limits incentives for industry investment.  Here, new initiatives are taking advantage of progress in gene targeting technologies to support the development of tailored disease-modifying therapies for rare disorders, including the NINDS Ultra-Rare Gene Therapy (URGenT) Network.  In these programs and others, NINDS aims to increase patient engagement in research to better address the priorities of patients and families and improve research efficiency and effectiveness.

Dysfunction in brain circuits contributes to a wide range of neurological, psychiatric, sensory, and substance use disorders.  Historically, limited knowledge about complex brain circuits and inadequate research tools for measuring circuit activity have impeded progress.  NINDS is a leader in the NIHBRAIN Initiative®, which is applying innovative technologies to learn how brain circuits work, capturing opportunities made possible by decades of investment in basic research and engineering.  The BRAIN Cell Census Network achieved a major milestone in releasing an atlas of cell types and a neuronal circuit diagram for the mammalian primary motor cortex, the brain’s main center for directing movement.  The BRAIN Initiative® is now launching a program to similarly map all of the human brain.  Moreover, advances that will benefit people with brain disorders are emerging from BRAIN Initiative® research, including a brain-controlled neuroprosthesis that allowed a paralyzed person to communicate in sentences, brain stimulation that halts seizures before they occur in people with epilepsy, and long-term wireless neural recordings for circuit discovery and adaptive brain stimulation in Parkinson's disease.

_______________________________________________

1 Baker RG, Koroshetz WJ, Volkow ND. The Helping to End Addiction Long-term (HEAL) Initiative of the National Institutes of Health. JAMA. 2021;326(11):1005–1006.

2Stroke Facts

### Committing to health equity, diversity, and inclusion across all of NINDS

The COVID-19 pandemic accentuated health disparities that exist across diseases and conditions, including neurological disorders.  Such inequities are associated with individuals’ racial or ethnic group, religion, socioeconomic status, gender, age, or mental health; sexual orientation or gender identity; cognitive, sensory, or physical disability; geographic location; or other characteristics historically linked to discrimination, stigmatization, or exclusion.  Although NINDS and NIH research has contributed to decades of declining stroke death rates overall, the risk of stroke is nearly twice as high for Black Americans as for White Americans, Black Americans have the highest rate of death due to stroke, and Hispanic Americans have seen a troubling increase in strokes since 2013.  These disparities may extend to neuro-degenerative disorders, given research linking cerebrovascular disease risks to the risk for cognitive impairment and dementia.3

NINDS has supported long-running epidemiological studies to define health inequalities in stroke as well as programs to test interventions that address contributors.  To help counter disproportionately high risk factors for stroke and dementia in Black Americans, NINDS updated its public health campaign on stroke awareness and prevention with messaging tailored to engage young Black men.  Yet, the persistence of health disparities demands we do more.  In 2020, NINDS began a planning process to build on prior efforts and promote research toward effective, scalable interventions targeting biologic and social determinants of health disparities across neurological disorders, with the ultimate goal of creating health equity.  As a culmination, NINDS hosted the Health Disparities and Inequities in Neurological Disorders Workshop (HEADWAY) in September 2021.  Findings and recommendations from the workshop and planning process will serve as resources for setting priorities and developing new initiatives.NINDS recognizes that diversity in the biomedical research workforce is vital to the NIH mission, and the NINDS Strategic Plan calls for enhancing diversity and inclusion at all research career stages, including through extramural and intramural programs to support training, mentoring, and career development and to address barriers to diversity among neuroscience research faculty.  In addition, the NIH BRAIN Initiative® now requires most grant proposals to include a Plan for Enhancing Diverse Perspectives (PEDP).4NINDS is also a committed partner in the NIH UNITE Initiative,5 an agency-wide effort to identify and address structural racism within the NIH and across the extramural scientific community.  These and other efforts to foster diversity will benefit neuroscience research by attracting the most talented researchers and staff from all groups; broadening perspectives in setting research priorities; increasing participation of people from diverse backgrounds in clinical research studies; strengthening capacity to address health disparities; and growing public trust in the work of NINDS and NIH.

_______________________________________________

3Stroke Facts; Mind Your Risks

4Plan for Enhancing Diverse Perspectives (PEDP)

5Ending Structural Racism - UNITE

### Meeting change with resilience: approaches to sustain and strengthen research

Measures necessary for responding to the COVID-19 pandemic had immediate and lasting impacts on biomedical research, as laboratory personnel stayed home and in-person visits for clinical research were put on hold.  Prior NINDS support for telemedicine in the treatment of neurological disorders such as stroke and Parkinson’s disease helped prepare clinical research teams to meet the challenges of the pandemic through increased use of telemedicine and other approaches to connect remotely with study participants and investigator teams.  Such approaches stand to enhance inclusion and health equity beyond the pandemic by increasing access to clinical research and care for underrepresented groups and underserved communities.  The COVID-19 pandemic has been especially disruptive for research trainees and investigators just embarking on their careers, broadly highlighting the need to support researchers to achieve their full potential even when challenging life events get in the way.  To limit the impact of these disruptions, NINDS extended eligibility for several training and career development programs and established requirements for academic institutions receiving NINDS research training grants to commit to family-friendly environments, leave policies, and accommodations for trainees.  Lessons learned and supports put in place will continue to foster a diverse workforce and positive work culture that will attract and retain skilled scientists into the future.

The urgent need for science-driven answers to COVID-19 underscored the value of collaboration in research.  NINDS has championed the use of Common Data Elements for clinical research on neurological conditions. These standards aid data sharing and improve data quality, and they helped to build clinical cohorts to study COVID-19.  The Accelerating Medicines Partnership: Parkinson's Disease (AMP-PD) program, the BRAIN Initiative®, and the Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics System are among NINDS and NIH neuroscience programs that are capitalizing on the power of big data, data sharing, and team science to tackle complex scientific problems.  NINDS and the National Institute of Allergy and Infectious Diseases (NIAID) also supported the recent development of data and biospecimen sharing platforms for ME/CFS research.  As data from new research technologies grow in scale and as machine learning, artificial intelligence, and analysis tools become more sophisticated, neuroscience research will face unprecedented opportunities and new challenges related to data curation, maintenance, and privacy.  A new NINDS Data Science Plan, aligned with the NIH Strategic Plan for Data Science, will inform NINDS efforts in this area.

## IC Fact Sheet

View IC Fact Sheet**(pdf, 2055 KB)

## Major Changes in the Budget Request

Major changes by budget mechanism and/or budget activity detail are briefly described below.  Note that there may be overlap between budget mechanism and activity detail, and these highlights will not sum to the total change for the FY 2023 President’s Budget request for NINDS, which is $2,768.0 million, an increase of $254.6 million from the FY 2022 CR level. The request includes $225.0 million provided by the 21st Century Cures Act.  Within the President’s Budget request level, NINDS will pursue its highest research priorities through strategic investments and careful stewardship of appropriated funds.

Research Project Grants (RPGs) (+$239.5 million; total $2,046.1 million):The NINDS budget reflects an increase of $239.5 million in the Research Project Grants portfolio, including SBIR/STTR awards. Competing RPGs are expected to increase by 193 grants in FY 2023 compared to the FY 2022 CR level of awards.

Other Research (-$3.0 million; total $175.9 million):The Other Research mechanism reflects a decrease due to Other Research grants converting to Research Project Grants.

Research and Development Contracts (+$7.9 million; total $134.2 million):NINDS plans to increase R&D contract funding to accommodate new and expanded contracts within the HEAL and Blueprint Neurotherapeutics Programs.

Research Management and Support (+$5.0 million; total $102.0 million):The NINDS budget reflects an increase of $5.0 million in Research Management and Support to provide additional staff and other support in recognition of recent increases in the NINDS grant portfolio.

## Budget Mechanism Table

### Budget Mechanism - Total 1,2

**(Dollars in Thousands)**

1 All items in italics and brackets are non-add entries.

2 Of which $50.0 million in FY 2021, $50.0 million in FY 2022, and $225.0 million in FY 2023 is derived by transfer from the NIH Innovation Account under the 21st Century Cures Act.

3 Includes $22.1 million of 21st Century Cures Act funding not obligated in FY 2021 and carried over into FY 2022.

## Appropriations Language

For carrying out section 301 and title IV of the PHS Act with respect to neurological disorders and stroke, $2,543,043,000.

**NIH INNOVATION ACCOUNT, CURES ACT (INCLUDING TRANSFER OF FUNDS)**

For necessary expenses to carry out the purposes described in section 1001(b)(4) of the 21st Century Cures Act, in addition to amounts available for such purposes in the appropriations provided to the NIH in this Act, $1,085,000,000, to remain available until expended: Provided, That such amounts are appropriated pursuant to section 1001(b)(3) of such Act, are to be derived from amounts transferred under section 1001(b)(2)(A) of such Act, and may be transferred by the Director of the National Institutes of Health to other accounts of the National Institutes of Health solely for the purposes provided in such Act: Provided further, That upon a determination by the Director that funds transferred pursuant to the previous proviso are not necessary for the purposes provided, such amounts may be transferred back to the Account: Provided further, That the transfer authority provided under this heading is in addition to any other transfer authority provided by law.

## Summary of Changes

### Summary of Changes

**(Dollars in Thousands)**

## Fiscal Year 2023 Budget Graphs

### History of Budget Authority and FTE's:

### Distribution of Mechanism:

### Change by Selected Mechanism:

## Organization Chart

## Budget Authority by Activity

### Budget Authority by Activity1

**(Dollars in Thousands)**

1 Includes FTEs whose payroll obligations are supported by the NIHCommon Fund.

2 Total for Opioid/Pain Research including IR and RMS is (in thousands) $269,484 in FY 2021, $270,295 in FY 2022, and $405,443 in FY 2023.

## Justification of Budget Request

### **Justification of Budget RequestNational Institute of Neurological Disorders and Stroke**

Authorizing Legislation: Section 301 and Title IV of the Public Health Service Act, as amended.

### Budget Authority (BA):

Program funds are allocated as follows: Competitive Grants/Cooperative Agreements; Contracts; Direct Federal/Intramural and Other.

Overall Budget Policy: The FY 2023 President's Budget request for NINDS is $2,768.0 million, an increase of $254.6 million or 10.1 percent compared to the FY 2022 CR level. The NINDS request includes 21st Century Cures Act funding $225.0 million for the BRAIN Initiative. The proposed increase in FY 2023 also includes an increase of $135.1 million for HEAL Initiative accompanied by a $43.0 million increase in other NINDS opioid and pain research.

## Program Descriptions

### Division of Neuroscience (DON)

As the largest part of the NINDS extramural program, DON supports research on the normal brain, spinal cord, and nerves of the body; mechanisms of neurological injury and disease; and early development of treatments and diagnostics. DON also supports research resources, core facilities, and scientific conferences. Investigator-initiated research driven by scientific opportunity is the foundation for the DON portfolio, and specific initiatives focus on topics and public health priorities that warrant a more targeted approach. DON program areas include:
              - Basic neuroscience research :  Gaps in understanding nervous system development and function and disease mechanisms hinder progress in treating and preventing neurological disorders. Basic research to fill those gaps is critical to the NINDS mission and is unlikely to receive sustained support from the private sector. Investing in basic research provides a broad foundation for future breakthroughs. For example, two basic neuroscientists supported by NINDS received the 2021 Nobel Prize in Physiology or Medicine. Over decades of research David Julius and Ardem Patapoutian identified receptors in nerve endings that trigger electrical impulses in response to temperature changes and mechanical force. Beyond unraveling mysteries about how we sense heat, touch, and body position, these fundamental discoveries are leading to new approaches for treating chronic pain and other conditions.  
              - NIH BRAIN Initiative®:   NINDS is a leading partner in the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, an ambitious effort to develop and apply new technologies to understand brain circuits and their functions, and ultimately to understand and treat brain diseases. Transformative projects underway will develop a comprehensive list of human brain cell types, complete a wiring diagram of mammalian brain circuits, and build an armamentarium of tools to access and modulate specific brain cell types and circuits to enable precision medicine applications in humans. (For more information, see the NIH Cross-Cutting Initiative section on the NIH BRAIN Initiative® in the NIH Congressional Justification Overview volume.)  
              - Neurodegeneration:   NINDS leads NIH research support for many neurodegenerative diseases. Programs for Parkinson’s disease include the Morris K. Udall Centers of Excellence; the Parkinson’s Disease Biomarkers Program (PDBP); and the Accelerating Medicines Partnership for Parkinson’s Disease (AMP-PD), which leverages patient cohorts and resources from PDBP and other programs to identify biomarkers and new targets for therapies. As part of the National Plan to Address Alzheimer’s Disease, NINDS leads NIH research on Alzheimer’s Disease Related Dementias (ADRD), which include Lewy Body dementia (LBD), frontotemporal dementia, vascular contributions to cognitive impairment and dementia (VCID), and mixed etiology dementias. Co-funding from the National Institute on Aging (NIA) enables support for specific initiatives and an extended payline for meritorious ADRD research proposals. NINDS is also partnering with the NIH Common Fund on the Accelerating Leading-edge Science in ALS (ALS2) initiative, which supported four new projects in 2021 on new mechanistic insights, finding target genes for therapeutic intervention, assessing a way to slow progression, and how environmental exposures contribute to ALS risk.  
              - Stroke and cerebrovascular disease: NINDS supports a broad portfolio of research to understand stroke causes and the mechanisms involved in stroke-related damage and repair, which might be harnessed to aid neuroprotection and recovery. NINDS established the Stroke Preclinical Assessment Network (SPAN) to rigorously test potential neuroprotective therapies in rodent models of acute ischemic stroke, with built-in replication studies across multiple laboratories to ensure unbiased results. Therapies that are successful in SPAN may later move into clinical trials through the NIH StrokeNet, a NINDS-funded network for stroke clinical trials. NINDS stroke research includes studies to understand small vessel disease (SVD) in the brain, which affects the brain’s small arteries and veins. In addition to stroke, SVD is a major cause of VCID. Together with NIA, NINDS also supports a national consortium called MarkVCID to develop and evaluate biomarkers that will help predict, diagnose, and track VCID.  
              - Rare diseases :  Many rare diseases affect the nervous system, and research on these disorders often yields insights into more common diseases with shared mechanisms. NINDS supports a large portfolio of research on rare diseases and is a partner in the NIH Rare Diseases Clinical Research Network, funding consortia for lysosomal disorders, mitochondrial diseases, dystonia, and others. NINDS has contributed to new treatments for rare disorders, including the first gene-based, disease-modifying therapies for spinal muscular atrophy and muscular dystrophy. An ongoing NINDS initiative aims to fill gaps in clinical trial readiness for rare neurological and neuro-muscular diseases with new therapies on the horizon, and a new initiative will support natural history and clinical outcome assessment studies for ultra-rare neurological diseases, meeting a critical need for therapy development. In FY 2023, NINDS will lead NIH support for a data management and coordinating center for the Undiagnosed Disease Network, enabling this successful program to continue past its initial NIH Common Fund support.  
              - Other neurological disorders :  DON research includes studies on many more nervous system disorders and on mechanisms shared across diseases, with studies informing new and improved treatments and diagnostics for hydrocephalus, spinal cord injury, traumatic brain injury (TBI), and neuropathies, among others. NINDS seeks input from research and patient communities to help set priorities, such as the Benchmarks for Epilepsy Research, updated in 2020. Because neuroscience spans scientific disciplines, NINDS also works closely with other NIH Institutes in areas of complementary interest. For example, in addition to having a leading role in the NIH HEAL InitiativeSM, NINDS is the primary NIH Institute for pain and headache research and leads the NIH Pain Consortium, which includes 23 Institutes and Centers. NINDS also leads NIH efforts focused on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), including support for multi-disciplinary research centers focused on understanding this complex disease and building research capacity. Additional areas of collaboration include developmental disorders such as cerebral palsy, autism, Fragile X Syndrome, and Down syndrome; muscular dystrophies; brain tumor; autoimmune conditions such as multiple sclerosis (MS); and infections that affect the nervous system, including acute and long-term effects of COVID-19.

**Budget Policy:** The FY 2023 President’s Budget request for the Division of Neuroscience is $1,620.8 million, an increase of $99.1 million, or 6.5 percent, from the FY 2022 CR level.

NINDS RESEARCH PROGRAM AWARD

Scientific discovery relies on creativity, hard work, persistence, and support for tackling difficult questions. Reaching a breakthrough can require long-term approaches, taking risks, or changing direction based on new findings, all of which can be difficult to support through traditional NIH funding mechanisms. For these reasons, NINDS launched a special program in 2016, the Research Program Award (R35).

This program allows investigators with a record of achievement the freedom to embark on ambitious, long-term research without the constraints of specific aims tied to a typical research project grant. It supports all of an investigator’s NINDS mission-relevant research with stable funding (up to $750,000 per year in direct costs) for up to eight years. Ultimately, the goal of the R35 program is to enable investigators to devote more time and creativity to the pursuit of cutting-edge neuroscience. With longer term research funding, the R35 mechanism helps to reduce the administrative burden of grant writing, allowing more opportunity for investigators to participate in the lab, mentor trainees, and explore new ideas and technologies.

Since the program’s inception, NINDS has funded 89 investigators from a variety of institutions, disciplines, and career stages who are pursuing broad and complex neuroscience questions. To encourage more diversity among program applicants and awardees, NINDS revised language in the notice of funding opportunity and increased social media outreach. These efforts resulted in more R35 applications from women, and in FY 2021, women received 39 percent of awards, up from 25 percent of prior awards.

### Division of Translational Research (DTR)

The DTR leads extramural NINDS therapy development through milestone-driven programs and services that support all development stages for drugs, devices, and biologic therapies, from preclinical studies to first-in-human clinical trials. Translational research is prone to failure and poses risks for private sector investment. DTR programs help to remove these risks by advancing therapies to a point of readiness sufficient for industry interest, or in some cases, for testing in NINDS-funded clinical trials. DTR will support the following programs in FY 2023: .
              - The  Blueprint Neurotherapeutics Network (BPN),  is led by NINDS for the NIH Blueprint for Neuroscience Research, a partnership of NIH Institutes and Centers that support neuroscience research. The BPN focuses on the development of small molecule drugs and biologic therapies. Successes to date include one compound tested in Phase II clinical trials to improve cognitive and memory function in Fragile X Syndrome and Alzheimer’s disease and another that has entered a Phase III trial for Stargardt disease, an inherited juvenile form of macular degeneration.  
              - The  Cooperative Research to Enable and Advance Translational Enterprises program (CREATE)  supports the development of biologic therapies, including large biological molecules, cell therapies, and gene therapies. Many therapies in CREATE are based on antisense oligonucleotides (ASOs) designed to modify the expression of specific genes, reflecting the promise of such precision medicine approaches for neurological diseases. Building on the success of the BPN for small molecule therapies, the  Blueprint Neurotherapeutics Network for Biologics (BPN-Biologics)  was established in 2021 as a broader platform for advancing biological therapies for nervous system diseases.  
              - The  Innovation Grants to Nurture Initial Translational Efforts (IGNITE)  program funds early-stage therapy development that fuels the pipeline for later stage programs, such as the BPN. IGNITE activities include assay validation, demonstration that therapies have sufficient biological activity to merit further study, and development of model systems for early testing.  
              - The NINDS  Ultra-rare Gene Therapy (URGenT)  Network will support precision medicine therapy development for serious, life-threatening ultra-rare neurological diseases affecting fewer than 20 in one million people. Together, these diseases represent a large medical need without available treatments and with little incentive for private sector therapy development.  
              - The  NINDS Biomarkers  supports development and validation of biomarkers, which can aid therapy development, clinical trials, and patient care decisions. Biomarkers are in later validation stages for MS diagnosis, TBI prognosis, and response to investigational therapy in GM1 gangliosidosis and Friedreich's ataxia. NINDS also leads a HEAL InitiativeSM biomarker program for pain conditions, with projects on prognostic/diagnostic markers for post-traumatic headache, chemotherapy-induced neuropathic pain, and adolescent musculoskeletal pain.  
              - The  Epilepsy Therapy Screening Program (ETSP)  screens candidate compounds from academia and industry in standardized animal models and has contributed to 11 drugs approved for common and rare epilepsies. Vigabatrin, identified by the ETSP as an antiseizure treatment, is now in an NINDS-funded clinical trial as an intervention to prevent or reduce the risk of infantile spasms and refractory seizures in infants with tuberous sclerosis. The ETSP aims to advance more treatments for drug-resistant epilepsy and disease prevention and modification.  
              - NINDS established the  Preclinical Screening Platform for Pain (PSPP)  within the HEAL Initiative SM  to identify and profile non-addictive therapeutics for acute and chronic pain.  
              - Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) Programs  support research by small businesses to develop therapies, diagnostics, and research tools relevant to the NINDS mission. Several DTR programs, as well as the NIH BRAIN and HEAL initiatives, include SBIR/STTR funding opportunities.  
              - The  NIH Countermeasures Against Chemical Threats (CounterACT)  program, funded by the NIH Office of the Director, develops medical countermeasures for toxic exposures after a chemical emergency and is part of the Chemical Countermeasures Research Program at NIAID. Several drug candidates have moved to advanced development, including midazolam, which received expanded FDA approval for reducing seizures after nerve agent exposure.

**Budget Policy:** The FY 2023 President’s Budget request for the Division of Translational Research is $197.0 million, an increase of $16.1 million, or 8.9 percent, from the FY 2022 CR level.

TRANSLATIONAL NEURAL DEVICES

The NINDS Translational Neural Devices program supports therapeutic and diagnostic device development for nervous system disorders, from preclinical studies through early-stage clinical trials. Building on historical NINDS contributions to effective devices, including the cochlear implant to restore hearing and deep brain stimulation for Parkinson’s disease, current initiatives support device development in academia and small businesses with milestone-driven funding to optimize success. Recent accomplishments include:
                  - An FDA-approved device that engages neuromodulatory circuits to improve motor and sensory function after stroke
                  - A device that restores respiratory muscle function in spinal cord injury
                  - A tiny wearable device for accurate, real-time seizure monitoring in epilepsy
                  - Advances to enable adaptable brain stimulation for Parkinson’s disease based on at-home recordings of patients’ brain activity and movement

In 2021, NINDS and the NIH Blueprint for Neuroscience Research announced the Blueprint MedTech program as an incubator for cutting-edge neurotechnology. The program will fund device optimization and clinical feasibility studies and provide access to resources such as translational research services and expert advice on issues such as regulatory submissions, commercialization, and strategic partnerships.

NINDS also leads neural device research within the NIHHEAL and BRAIN initiatives, leveraging shared expertise across these programs. The HEAL InitiativeSM is advancing devices for diagnosing and treating acute and chronic pain conditions, and the NIH BRAIN Initiative® supports the development of recording and stimulating devices to treat central nervous system disorders and better understand the human brain.

### Division of Clinical Research (DCR)

DCR supports clinical trials infrastructure and large-scale clinical research, including early and advanced phase clinical trials, comparative effectiveness research, and epidemiological studies for neurological conditions across the lifespan. To optimize clinical research, DCR enforces milestones for progress and provides resources to improve patient access and recruitment. In FY 2023, major DCR programs will include:

**NINDS clinical research networks** provide accessible infrastructure for efficient early and late stage clinical trials, bring together expert communities to promote high-quality research, enable partnerships with industry and patient groups, and help train future clinical trial investigators.
              - The  Network for Excellence in Neuroscience Clinical Trials (NeuroNext)  supports Phase II clinical trials to gather critical information about investigational treatments prior to larger late-stage trials, as well as studies to discover and validate biomarkers. Since 2011, NeuroNEXT has begun 10 studies focused on a range of common and rare neurological disorders. Completed trials have built evidence to justify later stage trials for treatments for MS, Huntington’s disease, and neuroprotection after acute stroke.
              - NIH StrokeNet  supports trials on stroke treatment, prevention, and recovery and rehabilitation through 25 regional centers and over 400 hospitals across the United States. Since 2014, 16 trials have been conducted or are ongoing through the network, with results informing clinical care. StrokeNet’s first pediatric trial is testing rehabilitation to improve upper extremity motor function in babies who had a perinatal stroke, and a new trial aims to find the first proven treatment for acute intracerebral hemorrhage (hemorrhagic stroke).
              - Strategies to Innovate EmeRgENcy Care Clinical Trials Network (SIREN),  led by NINDS and the National Heart Lung and Blood Institute (NHLBI), conducts clinical trials in emergency care for neurologic, cardiac, respiratory, and hematologic conditions. Ongoing trials are testing treatments for TBI and improving neurological outcomes after cardiac arrest. Another trial tested the safety and efficacy of convalescent plasma for preventing progression of mild COVID-19 to severe illness. NIH halted the trial when interim results showed no benefit, demonstrating SIREN’s ability to rapidly launch trials and deliver actionable results.
              - NINDS leads the  Early Phase Pain Investigation Clinical Network (EPPIC-Net)  for the HEAL InitiativeSM, for early phase trials of novel pain treatments.

The **Office of Global Health and Health Disparities** within DCR directs NINDS support for research on health disparities for neurological disorders and on minority, community, and global health relevant to the NINDS mission. An ongoing strategic planning process will guide and strengthen new NINDS investments in these areas.

The **NINDS Common Data Elements (CDE) Program** works with researchers, industry, nonprofit, other Federal agencies, and professional organizations to develop data standards for neurological disorders to foster collaboration and data sharing across studies and improve data quality and integrity. The program has developed CDEs for more than 20 disease areas, many with pediatric standards, and a common set for use across diseases.

**Budget Policy:** The FY 2023 President’s Budget request for the Division of Clinical Research is $128.4 million, a decrease of $4.6 million, or 3.5 percent, from the FY 2022 CR level.

### Division of Extramural Activities

DEA leads NINDS efforts in research training and career development, workforce diversity initiatives, and enhancing neuroscience rigor and reproducibility research. DEA also houses the NINDS Scientific Review Branch and is growing capacity to conduct and leverage analyses that inform the development and implementation of NINDS programs and policies.
              - The  Office of Training and Workforce Development  directs NINDS extramural research training and career development programs, including fellowships and mentored awards and grants for programs at academic institutions. Complementing NIH-wide programs, NINDS initiatives address unique training needs across neuroscience research career stages. Current initiatives include national research training programs for neurosurgeons and pediatric neurologists, career development awards for advanced trainees launching independent projects, and workshops focused on strengthening mentorship in neuroscience research.
              - The  Office of Programs to Enhance Neuroscience Workforce Diversity (OPEN)  promotes diversity in neuroscience research via programs designed to overcome barriers to the participation and inclusion of underrepresented or disadvantaged groups and individuals with disabilities. Programs span career stages from K-12 outreach to mentoring networks and funding opportunities targeting career transitions. NINDS is also a partner in the NIH Common Fund’s Faculty Institutional Recruitment for Sustainable Transformation (FIRST) program to foster inclusive excellence at NIH-funded institutions.
              - The  Office of Research Quality  promotes rigor and transparency in neuroscience research and has been instrumental to NIH and research journal policies to improve rigor in experimental design and transparent reporting in publications. New initiatives fund efforts to build, evaluate, and disseminate free and engaging educational resources on rigorous research principles.

**Budget Policy:** The FY 2023 President’s Budget request for the Division of Extramural Activities is $110.0 million, a decrease of $1.2 million, or 1.1 percent, from the FY 2022 CR level.

LANDIS MENTORSHIP AWARD

NINDS established the Landis Mentorship Award to recognize the critical role of excellent mentors in developing exceptional future scientists. The award is named for former NINDS Director Dr. Story Landis, who generously mentored others as they navigated their neuroscience careers.

Each year, NINDS selects Landis Awardees from grantees who show dedication to superior mentorship and training. NINDS invites nominations from current or former trainees who have first-hand knowledge of an individual’s influence as a mentor, with rotating requests for nominations for junior, mid-career, and senior investigator mentors. Awardees receive a $100,000 grant supplement to support their work to mentor additional neuroscience trainees.

Since 2018, NINDS has named 26 Landis Awardees who exemplify outstanding mentorship by cultivating mentees’ scientific excellence, investing in mentees’ professional development, and strengthening the research workforce through inclusion of people from diverse backgrounds. NINDS hopes the Landis Award shows the scientific community and academic institutional leaders in particular the high value NINDS places on training and mentorship. Further, NINDS hopes the award will encourage institutions to reward individuals not only for research achievements but also for their impact on the future of neuroscience through mentorship and training.

### Intramural Research Program (IRP)

The NINDS IRP conducts research and research training on the NIH campus. The IRP spans basic, translational, and clinical research in neuroscience, neurology, and neurosurgery and hosts core facilities providing state-of-the-art research technologies. With over 150 labs from NINDS and 10 other Institutes conducting neuroscience research at NIH, including many co-located in the Porter Neuroscience Research Center, the IRP offers a rich environment for collaboration.

The unique resources of the IRP enable innovative, multidisciplinary studies that bridge basic and clinical neuroscience to answer fundamental questions about the nervous system and its diseases. One recent study mapped brain activity in research volunteers as they learned a new skill and showed that during rest, the volunteers’ brains repeatedly replayed faster versions of the practiced activity. The more volunteers replayed the activity while at rest the better they performed during later practice, demonstrating that learning occurs during breaks from practice. Among other advances, IRP researchers built a cellular map of chronic MS lesions that points to treatment targets and found the cause of a form of childhood ALS – and a potential gene-silencing therapy.

NINDS intramural clinical studies benefit from the NIH Clinical Center, a hospital devoted solely to clinical research. NINDS leads a multisystem study on post-infectious ME/CFS to identify clinical and biological markers and disease mechanisms and will launch a study of veterans with Gulf War Illness (with the Veterans Health Administration) as well as a study of people with persistent symptoms long after acute COVID-19 infection. Other clinical studies focus on epilepsy, MS, neurodegenerative diseases, brain tumors, movement disorders, and rare genetic disorders; and they include early trials for drugs, devices, and gene therapy. In addition, NINDS helps find causes of puzzling neurological cases through the NIH Undiagnosed Diseases Program and works with local emergency departments on studies of acute stroke and TBI.

The Center for Alzheimer’s and Related Dementias (CARD) established by NIA and NINDS in 2020 aims to stimulate ambitious research that may be challenging to accomplish within traditional extramural funding mechanisms. Understanding the many ways genes linked to dementia affect cellular pathways will be essential for discovering strategies to prevent or halt neurodegeneration. As one of its first projects, CARD is using CRISPR/Cas9-based gene editing to create a repository of induced pluripotent stem cell lines that model over 100 different AD/ADRD gene variants. The cell lines will be freely available to the research community.

**Budget Policy:** The FY 2023 President’s Budget request for the Intramural Research Program is $235.5 million, an increase of $6.2 million, or 2.7 percent, from the FY 2022 CR level.

### Research Management and Support (RMS)

RMS comprises administrative, budgetary, logistical, and scientific support in the review, award, and monitoring of research grants, training awards, and research contracts. RMS also includes strategic planning, program evaluation, regulatory compliance, communication about NINDS research and neurological disorders, and liaison with other agencies, Congress, and the public. In 2021, NINDS updated its stroke prevention campaign (Mind Your Risks), based on evidence linking high blood pressure (hypertension) and the risk of dementia later in life. Messages on the importance of controlling hypertension aim to engage young Black men, as a step to addressing disproportionately high risks and risk factors for stroke and dementia in Black Americans.

**Budget Policy:** The FY 2023 President’s Budget request for Research Management and Support is $102.0 million, an increase of $5.0 million, or 5.1 percent, from the FY 2022 CR level.

### NIH Helping to End Addiction Long-termSM (HEAL) Initiative

The NIHHEAL InitiativeSM launched in 2018 as an aggressive, multi-agency effort to speed scientific solutions to stem the national opioid crisis. NINDS leads HEAL activities focused on new non-addictive medications and devices to treat acute and chronic pain conditions. These efforts include programs for pain biomarker discovery, preclinical therapy development, and a clinical trials network for testing potential therapies, all of which build on and integrate with NINDS programs and infrastructure for basic, translational, and clinical research.

**Budget Policy:** The FY 2023 President’s Budget request for NINDSHEAL funding is $405.4 million, an increase of $135.1 million, or 50.0 percent, from the FY 2022 CR level. NINDS HEAL funding for FY 2023 includes $374.3 million for extramural research, $20.0 million for intramural research, and $11.1 million for RMS.

## Appropriations History

1 Budget Estimates to Congress includes mandatory financing.

2 Includes funds derived by transfer from the NIH Innovation Account under the 21st Century Cures Act.

## Authorizing Legislation

## Amounts Available for Obligation

### Amounts Available for Obligation 1

**(Dollars in Thousands)**

1 Excludes the following amounts (in thousands) for reimbursable activities carried out by this account:FY 2021 - $24,954    FY 2022 - $25,000    FY 2023 - $25,000

2 Of which $70.0 million in FY 2020, $50.0 million in FY 2021, and $76.0 million in FY 2022 is derived by transfer from the NIH Innovation Account under the 21st Century Cures Act.

3 Reflects 21st Century Cures Act funding not obligated in FY 2020, and carried over into FY 2021.

## Budget Authority by Object Class

### Budget Authority by Object Class 1

**(Dollars in Thousands)**

1Includes FTEs whose payroll obligations are supported by the NIHCommon Fund.

## Salaries and Expenses

### Salaries and Expenses

**(Dollars in Thousands)**

## Detail of Full-Time Equivalent Employment (FTE's)

### Detail of Full-Time Equivalent Employment (FTE's)

### FTEs supported by funds from Cooperative Research and Development Agreements.

## Detail of Positions

### Detail of Positions1

***(Dollars in Thousands)***

1 Includes FTEs whose payroll obligations are supported by the NIHCommon Fund.