In the News

Research advances from the National Institutes of Health (NIH) Intramural Research Program (IRP) often make headlines. Read the news releases that describe our most recent findings:

IRP studies find severe symptoms of “Havana Syndrome,” but no evidence of MRI-detectable brain injury or biological abnormalities

Compared to healthy volunteers, affected U.S. government personnel did not exhibit differences that would explain symptoms

Using advanced imaging techniques and in-depth clinical assessments, a research team at the National Institutes of Health (NIH) found no significant evidence of MRI-detectable brain injury, nor differences in most clinical measures compared to controls, among a group of federal employees who experienced anomalous health incidents (AHIs). These incidents, including hearing noise and experiencing head pressure followed by headache, dizziness, cognitive dysfunction and other symptoms, have been described in the news media as 'Havana Syndrome' since U.S. government personnel stationed in Havana first reported the incidents. Scientists at the NIH Clinical Center conducted the research over the course of nearly five years and published their findings in two papers in JAMA today.

“Our goal was to conduct thorough, objective and reproducible evaluations to see if we could identify structural brain or biological differences in people who reported AHIs,” said Leighton Chan, M.D., chief, rehabilitation medicine and acting chief scientific officer, NIH Clinical Center, and lead author on one of the papers. “While we did not identify significant differences in participants with AHIs, it’s important to acknowledge that these symptoms are very real, cause significant disruption in the lives of those affected and can be quite prolonged, disabling and difficult to treat.”

Researchers designed multiple methods to evaluate more than 80 U.S. government employees and their adult family members, mostly stationed abroad, who had reported an AHI and compared them to matched healthy controls. The control groups included healthy volunteers who had similar work assignments but did not report AHIs. In this study, participants underwent a battery of clinical, auditory, balance, visual, neuropsychological and blood biomarkers testing. In addition, they received different types of MRI scans aimed at investigating volume, structure and function of the brain.

IRP researchers identify brain connections associated with ADHD in youth

Large study finds atypical interactions between the frontal cortex and information processing centers deep in the brain

Researchers at the National Institutes of Health (NIH) have discovered that symptoms of attention-deficit/hyperactivity disorder (ADHD) are tied to atypical interactions between the brain’s frontal cortex and information processing centers deep in the brain. The researchers examined more than 10,000 functional brain images of youth with ADHD and published their results in the American Journal of Psychiatry. The study was led by researchers at NIH’s National Institute of Mental Health (NIMH) and National Human Genome Research Institute (NHGRI).

Luke Norman, Ph.D., a staff scientist in the NIMH Office of the Clinical Director, and colleagues analyzed brain images supplied by more than 8,000 youth with and without ADHD sourced from six different functional imaging datasets. Using these images, the researchers examined associations between functional brain connectivity and ADHD symptoms.

They found that youth with ADHD had heightened connectivity between structures deep in the brain involved in learning, movement, reward, and emotion (caudate, putamen, and nucleus accumbens seeds) and structures in the frontal area of the brain involved in attention and control of unwanted behaviors (superior temporal gyri, insula, inferior parietal lobe, and inferior frontal gyri).

IRP scientists find weak points on Epstein-Barr virus

New details of EBV protein could aid treatment, prevention efforts

Studies of interactions between two lab-generated monoclonal antibodies (mAbs) and an essential Epstein-Barr virus (EBV) protein have uncovered targets that could be exploited in designing treatments and vaccines for this extremely common virus. The research was led by Jeffrey I. Cohen, M.D., and colleagues from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. Study findings were published in the journal Immunity.

Approximately 95% of the world’s population is infected with EBV, which remains in the body permanently, typically in B lymphocytes, which are antibody-producing immune system cells, and cells lining the throat and pharynx. EBV can sometimes lead to B-cell cancers, including Burkitt, Hodgkin and non-Hodgkin lymphomas, or to gastric or nasopharyngeal cancers. Recently, EBV infection was shown to significantly raise the risk of developing multiple sclerosis. There is no vaccine to prevent EBV infection nor a specific treatment.

In this study, NIAID investigators examined a viral protein called gp42, which the virus must use to infect B cells. Theoretically, a vaccine or antibody-based treatment capable of blocking gp42’s ability to bind to or fuse with B cells would prevent EBV infection and, thus, the virus’s ability to persist in those cells. The team generated two gp42-specific mAbs, A10 and 4C12, and used X-ray crystallography to visualize how they interacted with gp42. The crystal structures revealed that the two mAbs interacted with distinct, non-overlapping sites on gp42. Monoclonal antibody A10 blocked the site on gp42 required for receptor binding, while 4C12 interfered with a different site that is involved in membrane fusion.

An electron micrograph showing three Epstein-Barr virus (EBV) particles colorized pink

An electron micrograph showing three Epstein-Barr virus (EBV) particles colorized pink.

For childhood cancer survivors, inherited genetic factors influence risk of cancers later in life

NIH-led study sheds light on the causes of new cancers among childhood cancer survivors and could have implications for their screening and follow-up

Common inherited genetic factors that predict cancer risk in the general population may also predict elevated risk of new cancers among childhood cancer survivors, according to a study led by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health. The findings, published in Nature Medicine, provide additional evidence that genetics may play an important role in the development of subsequent cancers in survivors of childhood cancer and suggest that common inherited variants could potentially inform screening and long-term follow-up of those at greatest risk.

Childhood cancer survivors are known to have a higher risk of developing a new cancer later in life due to adverse effects of cancer treatment or rare inherited genetic factors. In the new study, the researchers evaluated the combined effect of common variants with history of radiation treatment and found the resulting elevated cancer risk was greater than the sum of the individual associations for treatment and genetic factors alone.

“Knowledge about a person’s genetic makeup could potentially be useful in managing their risk of subsequent cancers,” said lead investigator Todd M. Gibson, Ph.D., of NCI’s Division of Cancer Epidemiology and Genetics. “The hope would be that, in the future, we can incorporate genetics along with treatment exposures and other risk factors to provide a more complete picture of a survivor’s risk of subsequent cancers to help guide their long-term follow-up care.”

New antibodies target “dark side” of influenza virus protein

NIH researchers explore hidden, vulnerable region of influenza neuraminidase

Researchers at the National Institutes of Health have identified antibodies targeting a hard-to-spot region of the influenza virus, shedding light on the relatively unexplored “dark side” of the neuraminidase (NA) protein head. The antibodies target a region of the NA protein that is common among many influenza viruses, including H3N2 subtype viruses, and could be a new target for countermeasures. The research, led by scientists at the National Institute of Allergy and Infectious Diseases’ Vaccine Research Center, part of NIH, was published today in Immunity.

Influenza, or flu, sickens millions of people across the globe each year and can lead to severe illness and death. While vaccination against influenza reduces the burden of the disease, updated vaccines are needed each season to provide protection against the many strains and subtypes of the rapidly evolving virus. Vaccines that provide protection against a broad range of influenza viruses could prevent outbreaks of new and reemerging flu viruses without the need for yearly vaccine reformulation or vaccinations.

One way to improve influenza vaccines and other countermeasures is to identify new targets on the virus’s surface proteins in “conserved” regions — portions that tend to be relatively unchanged between different strains of the virus. Influenza NA is a surface protein containing a globular head portion and a narrow stalk portion. The underside of the NA head contains a highly conserved region with targets for antibodies — known as epitopes — that make it vulnerable to antibody binding and inhibition of the virus, as well as not being impacted by mutations common in drug-resistant strains. This region is termed the “dark side” due to its partially hidden location and relatively unexplored characteristics.

IRP study offers new clues into the causes of post-infectious ME/CFS

In-depth study finds brain, immune, and metabolic abnormalities linked to debilitating chronic disease

In a detailed clinical study, researchers at the National Institutes of Health have found differences in the brains and immune systems of people with post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS). They also found distinct differences between men and women with the disease. The findings were published in Nature Communications.

“People with ME/CFS have very real and disabling symptoms, but uncovering their biological basis has been extremely difficult,” said Walter Koroshetz, M.D., director of NIH’s National Institute of Neurological Disorders and Stroke (NINDS). “This in-depth study of a small group of people found a number of factors that likely contribute to their ME/CFS. Now researchers can test whether these findings apply to a larger patient group and move towards identifying treatments that target core drivers of the disease.”

A team of multidisciplinary researchers discovered how feelings of fatigue are processed in the brains of people with ME/CFS. Results from functional magnetic resonance imaging (fMRI) brain scans showed that people with ME/CFS had lower activity in a brain region called the temporal-parietal junction (TPJ), which may cause fatigue by disrupting the way the brain decides how to exert effort.

Researchers identify brain hub with key role in learned response to direct and indirect threats

NIH-supported study in mice could inform treatments of trauma- and stress-related psychiatric conditions

Scientists have identified an area within the brain’s frontal cortex that may coordinate an animal’s response to potentially traumatic situations. Understanding where and how neural circuits involving the frontal cortex regulate such functions, and how such circuits could malfunction, may provide insight about their role in trauma-related and stress-related psychiatric disorders in people. The study, led by scientists at the National Institute on Alcohol Abuse and Alcoholism (NIAAA), a part of the National Institutes of Health, was published in Nature.

“Experiencing traumatic events is often at the root of trauma-related and stress-related psychiatric conditions, including alcohol use disorder (AUD),” said the study’s senior author, Andrew Holmes, Ph.D., senior investigator in NIAAA’s Laboratory of Behavioral and Genomic Neuroscience. “Additionally, witnessing others experience traumatic events can also contribute to these disorders.”

In animal models of stress and trauma, learning about potential sources of threat by observing how others deal with danger can be an effective way to avoid harm. Understanding the differences in how the brain processes direct experience of a threat compared to observing another’s response to a threat may shed light on factors that predispose humans to trauma- and stress-related psychiatric disorders.

Diagram of mouse prefrontal cortex showing neural projections to the midbrain (purple) and the amygdala (green), pathways involved in learning about threat

Diagram of mouse prefrontal cortex showing neural projections to the midbrain (purple) and the amygdala (green), pathways involved in learning about threat.

NIH selects Dr. Sean Mooney as director of the Center for Information Technology

National Institutes of Health Director Monica M. Bertagnolli, M.D., has named Sean Mooney, Ph.D., as director of NIH’s Center for Information Technology (CIT). Dr. Mooney is expected to join NIH in mid-March.

“Dr. Mooney has spent his career developing effective and collaborative computing systems to support biomedical research. His background in bioinformatics and expertise in the implementation and governance of a multi-faceted research IT department make him particularly suited to lead NIH CIT,” said Dr. Bertagnolli. “I look forward to welcoming Dr. Mooney to the NIH leadership team and extend my gratitude to Ivor D’Souza who is serving as acting director of CIT following the retirement of former director Andrea Norris in September 2022.”

As CIT director, Dr. Mooney will oversee an approximately $400 million portfolio that includes a world-renowned supercomputer that allows researchers to conduct large-scale data analyses; a state-of-the-art network that enables research across NIH and around the world; cloud-based services that give researchers a cost-effective way to access datasets and advanced computational tools and services; and the latest collaboration tools to promote flexibility and productivity. CIT collaborates with the NIH intramural community in computational bioscience, engineering, informatics and statistics to help make biomedical discoveries that protect and improve our nation’s health. Additionally, CIT provides IT infrastructure and IT services to support all of NIH.

Dr. Sean Mooney

Dr. Sean Mooney

New direct links discovered between the brain and its surrounding environment

NIH collaboration has implications for neural-immune system responses and aging

In a recent study of the brain’s waste drainage system, researchers from Washington University in St. Louis, collaborating with investigators at the National Institute of Neurological Disorders and Stroke (NINDS), a part of the National Institute of Health (NIH), discovered a direct connection between the brain and its tough protective covering, the dura mater. These links may allow waste fluid to leave the brain while also exposing the brain to immune cells and other signals coming from the dura. This challenges the conventional wisdom which has suggested that the brain is cut off from its surroundings by a series of protective barriers, keeping it safe from dangerous chemicals and toxins lurking in the environment.

“Waste fluid moves from the brain into the body much like how sewage leaves our homes,” said NINDS’s Daniel S. Reich, M.D., Ph.D. “In this study, we asked the question of what happens once the ‘drain pipes’ leave the ‘house’ — in this case, the brain — and connect up with the city sewer system within the body.” Reich’s group worked jointly with the lab of Jonathan Kipnis, Ph.D., a professor at Washington University in St. Louis.

Reich’s lab used high-resolution magnetic resonance imaging (MRI) to observe the connection between the brain and body’s lymphatic systems in humans. Meanwhile Kipnis’s group was independently using live-cell and other microscopic brain imaging techniques to study these systems in mice.

MRI images showing fluid containing light-emitting molecules slipping through the arachnoid barrier where blood vessels pass through

Fluid containing light-emitting molecules was seen to slip through the arachnoid barrier where blood vessels passed through.

Abnormal proteins found in the spinal fluid of people with ALS and frontotemporal dementia

Proteins could serve as biomarkers that improve diagnosis and guide the development of novel therapies

Researchers at the National Institutes of Health detected abnormal proteins in the spinal fluid of people with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), which could help improve diagnosis of these diseases. The findings were published in Science Translational Medicine.

The proteins in question are built from 'cryptic' exons — abnormal portions of RNA, the cell’s instructions for how to build proteins. Cryptic exons occur when TDP-43, a protein that regulates how RNA is processed, stops functioning normally. TDP-43 dysfunction is linked to ALS, FTD, Alzheimer’s disease, and Limbic Associated TDP-43 Encephalopathy (LATE).

The study showed that these mis-spliced sections of RNA can sometimes generate new proteins from the cryptic sequence. The findings advance our understanding of how cryptic exons may be involved in the dementia disease process and could help identify diseases involving TDP-43 dysfunction before symptoms appear. Currently, TDP-43 aggregates in the brain can only be detected at autopsy.

Protein containing a cryptic peptide (red) that results from a lack of functional TDP-43

Protein containing a cryptic peptide (red) that results from a lack of functional TDP-43, as in ALS and FTD.

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This page was last updated on Wednesday, May 11, 2022