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Three in four sepsis survivors experience new-onset memory problems, psychological impairments or physical diagnoses. This also applies to more than half of sepsis survivors under the age of 40 at the time of their discharge from hospital. These are just two of the findings of a retrospective analysis of anonymized health claims data conducted by a team of researchers from Charité — Universitätsmedizin Berlin, Jena University Hospital and the research institute of the Local Health Care Funds (AOK). The study, which explores the frequency and costs of postsepsis morbidity, has been published in JAMA Network Open.
The term ‘sepsis’ refers to dangerous organ dysfunction caused by an exaggerated immune response to infection. Sepsis is a life-threatening medical emergency which develops when the body’s response to an infection causes extensive tissue damage, preventing organs like the kidneys or liver from functioning properly. Worldwide, sepsis is the leading cause of death related to infection. A total of 320,000 cases of sepsis are treated in German hospitals every year. In-hospital mortality is alarmingly high, standing at approximately 25 percent. According to recent studies, the majority of patients with severe COVID-19 develop sepsis.
Findings obtained by the Center for Sepsis Control and Care (CSCC) at Jena University Hospital (UKJ) have been pivotal in fostering collaborative endeavors combining patient-oriented basic research with clinical research in the field of sepsis. Other research interests include rehabilitation and the long-term consequences of severe disease. An interdisciplinary post-COVID center is currently in development. The current study investigating sepsis-related morbidity, risk factors, treatment and costs is the result of a partnership between the UKJ and Charité, which is funded via the Federal Joint Committee’s German Innovation Fund (Innovationsfonds). For this research, the two partners also joined forces with WIdO, the AOK’s research institute.
The study team had access to the anonymized health data of more than 23 million people insured with the German health insurance provider AOK between 2008 and 2017. The researchers identified 159,684 individuals aged 15 years or older who were hospitalized with sepsis during 2013 or 2014, receiving treatment on either a normal or intensive care ward. For each of these patients, the researchers collated data on prior morbidities as well as data on new diagnoses recorded during the three years post sepsis. They also recorded any relevant post-sepsis treatment and care needs. “As part of our analysis, we looked for new physical, psychological and cognitive impairments which are known to develop as a result of sepsis, including cardiovascular disorders, cognitive and motor impairments, fatigue and depression,” says project lead Dr. Carolin Fleischmann-Struzek.
Three out of four sepsis survivors recorded a new diagnosis during the first year after discharge; more than 30 percent of sepsis survivors died during this time period. Among younger patients (aged under 40 years), the proportion of people who developed post-sepsis complications was 56 percent. Expanding on the frequency of health complications, the study’s last author, Prof. Dr. Christiane Hartog, a health services researcher at Charité’s Department of Anesthesiology and Intensive Care Medicine, emphasizes: “The majority of survivors experience psychological, cognitive and physical symptoms. The fact that these often occur together only increases the severity of their impact. Surprisingly, there appears to be very little difference between individuals whose sepsis was less severe and individuals who needed intensive care. This finding may have particular relevance to individuals with post-COVID syndrome.”
The researcher also analyzed costs associated with inpatient and outpatient treatments, rehabilitation, treatments (such as physical or occupational therapy) and drugs. Average treatment costs amounted to a total of €29,000 for the first three years after discharge. This total included emergency and transport costs, medical supplies, care costs and indirect costs such as absence from work. More than 30 percent of sepsis survivors were newly dependent on nursing care during the first year following their discharge from hospital, while 13 percent of survivors of severe sepsis were newly dependent on residential care. The researchers also note the dearth of adequate follow-up care. Only 5 percent of sepsis survivors were discharged into inpatient rehabilitation facilities. “The impact of sepsis is enormous and lasts for years — and it is felt by survivors, their families and the health care system,” says Dr. Fleischmann-Struzek “For this reason, we need specific care concepts for post sepsis follow-up.”
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A molecule that shows promise in preventing Parkinson’s disease has been refined by scientists at the University of Bath in the UK, and has the potential to be developed into a drug to treat the deadly neurodegenerative disease.
Professor Jody Mason, who led the research from the Department of Biology and Biochemistry at Bath, said: “A lot of work still needs to happen, but this molecule has the potential to be a pre-cursor to a drug. Today there are only medicines to treat the symptoms of Parkinson’s — we hope to develop a drug that can return people to good health even before symptoms develop.”
Parkinson’s Disease is characterised by a specific protein in human cells ‘misfolding’, where it becomes aggregated and malfunctions. The protein — alpha-synuclein (αS) — is abundant in all human brains. After misfolding, it accumulates in large masses, known as Lewy bodies. These masses consist of αS aggregates that are toxic to dopamine-producing brain cells, causing them to die. It is this drop in dopamine signalling that triggers the symptoms of Parkinson’s Disease, as the signals transmitting from the brain to the body become noisy, leading to the distinctive tremors seen in sufferers.
Previous efforts to target and ‘detoxify’ αS-induced neurodegeneration have seen scientists analyse a vast library of peptides (short chains of amino acids — the building blocks of proteins) to find the best candidate for preventing αS misfolding. Of the 209,952 peptides screened in earlier work by scientists at Bath, peptide 4554W showed the most promise, inhibiting αS from aggregating into toxic disease forms in lab experiments in solutions and on live cells.
In their latest work, this same group of scientists tweaked peptide 4554W to optimise its function. The new version of the molecule — 4654W(N6A) — contains two modifications to the parental amino-acid sequence and has proven to be significantly more effective at reducing αS misfolding, aggregation and toxicity. However, even if the modified molecule continues to prove successful in lab experiments, a cure for the disease is still many years away.
Dr Richard Meade, the study lead author, said: “Previous attempts to inhibit alpha synuclein aggregation with small molecule drugs has been unfruitful as they are too small to inhibit such large protein interactions. This is why peptides are a good option — because they are big enough to prevent the protein from aggregating but small enough to be used as a drug. The effectiveness of the 4654W(N6A) peptide on alpha synuclein aggregation and cell survival in cultures is very exciting, as it highlights that we now know where to target on the alpha synuclein protein to supress its toxicity. Not only will this research lead to the development of new treatments to prevent the disease, but it is also uncovering fundamental mechanisms of the disease itself, furthering our understanding of why the protein misfolds in the first place.”
Professor Mason added: “Next, we’ll be working to how we can take this peptide to clinic. We need to find ways to modify it further so it’s more drug-like and can cross biological membranes and get into the cells of the brain. This may mean moving away from naturally occurring amino acids towards molecules that are made in the lab.”
This research also has implications for Alzheimer’s disease, Type 2 diabetes and other serious human diseases where symptoms are triggered by protein misfolding.
Dr Rosa Sancho, head of research at Alzheimer’s Research UK, said: “Finding ways to stop alpha synuclein from becoming toxic and damaging brain cells could highlight a new pathway for future drugs to stop devastating diseases like Parkinson’s and dementia with Lewy bodies.
“We’re pleased to have supported this important work to develop a molecule that can stop alpha synuclein from misfolding. The molecule has been tested in cells in the laboratory and will need further development and testing before it can be made into a treatment. This process will take a number of years, but it is a promising discovery that could pave the way for a new drug in future.
“Currently there are no disease-modifying treatments available for Parkinson’s disease or dementia with Lewy bodies, which is why continued investment in research is so important for all those living with these diseases.”
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A study led by the National Eye Institute (NEI) that included five researchers from the Bazan Lab at the LSU Health New Orleans Neuroscience Center of Excellence has discovered how late-onset retinal degeneration can develop and a surprising potential therapeutic — metformin. The results are published online in Communications Biology, a Nature journal.
Late-onset retinal degeneration is an autosomal dominant disorder caused by the substitution of a different amino acid in the protein made by the CTRP5 gene. Earlier discoveries by LSU Health Neuroscience researchers on retina lipids that protect sight helped lay the groundwork for the current study. Their collaborative data suggest a mechanism for the dominant behavior of the CTRP5 gene mutation, which had been unclear.
The protein made by CTRP5 has been identified as a biomarker for obesity and chronic obstructive pulmonary disease, suggesting a role for this protein in regulating cellular fatty acid metabolism. It has been suggested that an enzyme called 5’AMP-activated protein kinase (AMPK) activates CTRP5 to regulate fatty acid metabolism and energy stability. Retinal pigment epithelium (RPE) cells take up photoreceptor outer segments, which have an abundance of fatty acids and lipids.
“Increasing evidence demonstrates that the tips of visual cells that are daily shed in RPE cells convert docosahexaenoic acid (DHA) into Neuroprotectin D1 (NPD1) and other mediators that protect the photoreceptors from photooxidative damage and consequences of mutations such as the one studied here,” notes Nicolas Bazan, MD, PhD, Boyd Professor and Director of LSU Health New Orleans Neuroscience Center of Excellence. “AMPK in the RPE itself is a key regulator of the conversion of DHA into protective mediators.”
It has been suggested that dysregulation of fatty-acid and lipid metabolism contributes to the atrophy of RPE cells found in age-related macular degeneration. The study found this in cells from patients with late-onset retinal degeneration, as well as reduced secretions of CTRP5. Lower CTRP5 levels are associated with sustained activation of AMPK, which leads to its insensitivity to changes in the cellular energy status.
“Mechanistically, reduced secretion of CTRP5 and predicted lower binding affinity of mutant CTRP5 to the receptor for the gene that makes lipoproteins that carry fats in the bloodstream is the likely reason for the genetically dominant behavior of this disease,” says Dr. Bazan, who also holds the Ernest C. and Yvette C. Villere Chair for the Study of Retinal Degeneration.
The researchers demonstrated that a gene therapy approach — overexpressing CTRP5 — overcame lower levels of CTRP5 secretion in the cells of patients with late-onset retinal degeneration. They also tested the anti-diabetic drug metformin to determine if it influenced AMPK activity and could reverse RPE deterioration. Metformin has been shown to delay retinal degeneration in mice and to protect the RPE. The researchers found that metformin was effective in re-sensitizing AMPK to changes in cellular stress, restoring energy stability, and alleviating the disease’s cellular phenotypes.
Bazan concludes, “The study offers novel insights into the role of CTRP5 in the RPE and how the pathogenic variant in late-onset retinal degeneration causes dominant disease and provides further evidence that metformin can be a beneficial intervention for its treatment.”
The LSU Health New Orleans researchers also include Drs. Bokkyoo Jun, Khanh V. Do, Marie-Audrey Kautzman Guerin, and Jorgelina Calandria, of the Neuroscience Center of Excellence. Other authors were from the National Eye Institute and the University of Pennsylvania.
The research was supported by the National Eye Institute of the National Institutes of Health and the Eye Ear Nose Throat (EENT) Foundation of New Orleans.
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A diet rich in plant products reduces the risk of cognitive impairment and dementia in the elderly. This is the result of a study by the Biomarkers and Nutritional Food Metabolomics Research Group of the Faculty of Pharmacy and Food Sciences of the University of Barcelona (UB) and the CIBER on Frailty and Healthy Aging (CIBERFES).
The paper, published in the journal Molecular Nutrition and Food Research, is led by Cristina Andrés-Lacueva, professor at the Faculty of Pharmacy and Food Sciences and head of the Biomarkers and Nutritional Metabolomics of Food Research Group of the UB and the Biomedical Research Network Center in Frailty and Healthy Aging (CIBERFES), which is also part of the Food Innovation Network of Catalonia (XIA).
This European study, part of the Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL), was carried out over 12 years with the participation of 842 people aged over 65 in the Bordeaux and Dijon regions (France).
Metabolomics to study the impact of diet on health
The study analyses the relationship between the metabolism of dietary components, intestinal microbiota, endogenous metabolism and cognitive impairment. As Mireia Urpí-Sardà, from the Department of Nutrition, Food Science and Gastronomy and CIBERFES, notes, “what we analysed in the cohorts under study is the modulating role of the diet in the risk of suffering cognitive impairment.” Urpí-Sardà points out that “the results show a significant association between these processes and certain metabolites.”
The results reveal a protective association between metabolites derived from cocoa, coffee, mushrooms and red wine, microbial metabolism of polyphenol-rich foods (apple, cocoa, green tea, blueberries, oranges or pomegranates) and cognitive impairment in the elderly.
The analysis of plasma samples indicated that some metabolites are related to the progression of cognitive impairment and dementia. As Professor Cristina Andrés-Lacueva explains, “for example, 2-furoylglycine and 3-methylanthine, which are biomarkers of coffee and cocoa consumption, had a protective profile, while saccharin -derived from the consumption of artificial sweeteners- is associated with a damaging role.”
Mercè Pallàs, professor at the Faculty of Pharmacy and Food Sciences and member of the Institute of Neurosciences (UBNeuro) of the UB, stresses that “the study of the relationship between cognitive impairment, the metabolism of the microbiota and food and endogenous metabolism is essential to develop preventive and therapeutic strategies that help to take care of our cognitive health.”
Dietary changes for a healthy cognitive aging
Therefore, changes in lifestyle and diet are decisive as a strategy to prevent cognitive deterioration and its progression in neurodegenerative diseases such as Alzheimer’s and other dementias. “A higher intake of fruits, vegetables and plant-based foods provides polyphenols and other bioactive compounds that could help reduce the risk of cognitive decline due to ageing,” says Cristina Andrés-Lacueva.
Teams from the Department of Pharmacology, Toxicology and Therapeutic Chemistry of the Faculty of Pharmacy and Food Sciences, and the Department of Genetics, Microbiology and Statistics of the Faculty of Biology have also participated in the study. The University of Bordeaux and the INRAE Center of the University Clermont-Ferrand (France), King’s College London (United Kingdom), the University of Amsterdam (Netherlands) and the Paracelsus Medical Private University (Austria) have also collaborated in the study. The research has received funding from the International Joint Programming Actions PCIN-2015-229, from the European Regional Development Funds (ERDF) and from the former Ministry of Economy, Industry and Competitiveness (MINECO), through the Joint Programming Initiative “A Healthy Diet for a Healthy Life.”
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Hospitalized COVID-19 patients who had been chronically exposed in their neighborhoods to higher particulate matter — such as smoke, soot, and dirt — had increased risks for admission to the intensive care unit (ICU) and death compared to those without such exposure, Mount Sinai-led researchers reported in the American Journal of Respiratory and Critical Care Medicineon December 8.
The finding adds to our understanding about environmental factors that increase the risks of COVID-19. The researchers noted that chronic air pollution exposure can alter the pulmonary immune system, may increase systemic inflammation, and can be associated with increased risk for cardiovascular disease and metabolic syndrome. COVID-19 infections and deaths have also disproportionately occurred among Black, Latinx, and Indigenous populations, as well as among individuals with risk factors based on sex, age, and existing comorbid diseases such as diabetes and obesity.
“The COVID-19 pandemic has brought to the forefront the critical role of the environment on health disparities. These data suggest that long-term exposure to air pollution, even at concentrations below U.S. Environmental Protection Agency regulatory standards, is associated with higher COVID-19 morbidity and mortality amongst hospitalized patients,” said corresponding author Alison Lee, MD, MS, Assistant Professor of Medicine (Pulmonary, Critical Care and Sleep Medicine), and Pediatrics, at the Icahn School of Medicine at Mount Sinai. “Critically, air pollution is a modifiable risk factor. Policies to reduce air pollution must be considered a necessary public health measure, especially in communities that are disproportionately susceptible to air pollution’s deleterious effects.”
A team of researchers conducted a retrospective analysis of more than 6,500 COVID-19 patients admitted to seven New York City hospitals with ethnically diverse patient populations — including Mount Sinai Morningside, Mount Sinai Queens, NYC Health + Hospitals/Elmhurst, and NYC Health + Hospitals/Queens — amid the first peak of the pandemic from March to August 2020. The researchers estimated exposure levels to pollutants including particulate matter, nitrogen dioxide, and black carbon at the residential addresses of the patients at the time of admission. The team then assessed patient outcomes including mortality, ICU admission, and intubation. They found that chronic exposure to particulate matter, even at levels below current regulatory thresholds, was associated with an 11 percent higher risk of mortality and 13 percent higher risk of admission to the ICU. Exploratory analyses suggested that younger people of color may be particularly susceptible.
The study was developed through participation in the COVID-19 Unit for Research at Elmhurst (CURE-19) partnership, an initiative by Mount Sinai’s Arnhold Institute for Global Health and NYC Health + Hospitals/Elmhurst and Queens to research the global pandemic and root causes of health disparities in New York City.
“There is a lot we still don’t know about coronavirus, and that is why initiatives like the CURE-19 partnership are of utmost importance in the fight against this pandemic and our continued recovery,” said co-author Stanley Pierre, MD, MPA, NYC Health + Hospitals/Queens Patient Safety Coordinator and Director of the Clinical Centers of Excellence Development Program. “Being able to better understand what and how environmental factors play a role in New Yorkers’ health and COVID-19-associated risks not only allow us to better treat patients in the long-term, but also give us the opportunity to advocate for broader changes that can help prevent serious illness in the future.”
In addition to researchers from CURE-19, experts from Columbia University and the University of California, Berkeley contributed to the study. It was supported by grants from the National Institute on Minority Health and Health Disparities (R01MD013310), the National Institute of Environmental Health Sciences (P30ES023515, P30ES009089), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (P2CHD058486), and the National Heart, Lung and Blood Institute (K23HL135349).

DNA (deoxyribonucleic acid) contains the genetic information required for the development and maintenance of life. This information is communicated by messenger ribonucleic acid (mRNA) to make proteins. mRNA-based therapeutics have the potential to address unmet needs for a wide variety of diseases, including cancer and cardiovascular disease. mRNA can be delivered to cells to trigger the production, degradation or modification of a target protein, something impossible with other approaches. A key challenge with this modality is being able to deliver the mRNA inside the cell so that it can be translated to make a protein. mRNA can be packed into lipid nanoparticles (LNPs) ¬- small bubbles of fat ¬- that protect the mRNA and shuttle it into cells. However, this process is not simple, because the mRNA has to pass the membrane before it can reach its site of action in the cell interior, the cytoplasm.
Researchers in the team of MPI-CBG director Marino Zerial are experts in visualizing the cellular entry routes of molecules in the cell, such as mRNA with high-resolution microscopes. They teamed up with scientists from AstraZeneca who provided the researchers with lipid nanoparticle prototypes that they had developed for therapeutic approaches to follow the mRNA inside the cell. The study is published in the Journal of Cell Biology.
“To be delivered, the mRNA must make a long journey. Enclosed in the fatty LNP bubble, it needs to get into the cell first,” explains Marino Zerial. “The LNPs arrive at the cell surface where they bind to receptors. They are then taken up into specialized membrane-enclosed compartments called endosomes. At this point, the mRNA is inside the cells but surrounded by two barriers, the fatty bubble and the endosome wall or more correctly, membrane. The challenge for the mRNA is to escape both barriers to reach the cytoplasm where it serves as a template to make proteins. We know that only a tiny fraction of RNA molecules are able to escape into the cytoplasm.” Internalized cargo molecules, like the LNPs, are first transported to “early” endosomes. These are logistic centres that distribute cargo molecules to various destinations in the cell. They either recycle molecules to the cell surface or degrade them in late endosomes and lysosomes. So far, people thought that the mRNA escapes from late endosomes exploiting their very acidic content. “With single molecule microscopy techniques,” explains Prasath Paramasivam, the first author of the study, “we could visualize for the first time the mRNA in the LNP inside the endosomes of cells. We also captured the actual escape of the mRNA, which happened in the tubules of the recycling endosomes, which are only mildly acidic.” “Our results imply that sending the LNP-mRNA to late endosomes is counterproductive for delivery and only increases cell toxicity.” says Zerial. These findings help understanding the mechanism of mRNA escape from endosomes in more detail.
Marino Zerial summarizes: “The LNP delivery system for mRNA necessitates high doses due to the low endosomal escape efficiency. Knowing where the mRNA goes and how it can escape the endosomes allows us to develop better vehicles for more efficient delivery, at lower dosage. We can improve the mRNA delivery system so it can be used for therapeutic applications, for example cancer treatment.”
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Materials provided by Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG). Note: Content may be edited for style and length.

A team of physicists working at the intersection of theory and experiment are shedding new light on the “teamwork” of molecular motors — called RNA polymerases (RNAPs) — that mediate DNA transcription. During transcription, the first step in gene expression, RNAPs “read” DNA sequences and assemble messenger RNA (mRNA), which in turn serves as the template for the proteins necessary for life.
The team — comprising lead author Purba Chatterjee , a recent Illinois Physics Ph.D. graduate, now a postdoctoral researcher at University of Pennsylvania; Illinois Physics Emeritus Research Professor Nigel Goldenfeld, now the Chancellor’s Distinguished Professor of Physics at University of California San Diego; and Illinois Physics Professor Sangjin Kim — introduces a new theoretical model elucidating how the mechanism of supercoiling in DNA underlies the collective dynamics of RNAPs that are concurrently translocating on the DNA for transcription. The RNAPs dynamics switch from cooperative to antagonistic mode, in response to the cell’s needs.
These findings were published on November 16, 2021,in the article “DNA Supercoiling Drives a Transition between Collective Modes of Gene Synthesis,” in the journal Physical Review Letters.
During transcription, DNA supercoiling occurs when torsional stress is introduced by the unzipping of a portion of the helix into two strands, one of which will be transcribed. The researchers’ work revealed for the first time two essential elements in modeling transcription under torsion: first, transcription factors that are well known to affect the rate at which RNAP initiate transcription can also control the propagation of DNA supercoils, and second, the number of RNAPs present affects the torsional stress experienced by individual RNAPs.
Goldenfeld explains, “Supercoiling is something familiar to anyone who has wrestled with a garden hose or, in times past, a telephone cord. Semi-rigid tubes or, in this case, helices are difficult to fold and they bend into localized tangles — loops that can look like figure eights or worse. Biology battles with the same geometrical issues at the DNA molecular level within living cells.”
Once an RNAP initiates transcription, it translocates along the strand, assembling a complementary strand of mRNA. Additional RNAPs are recruited, each RNAP initiating mRNA synthesis along the same segment of DNA. The rate of the subsequent RNAP initiations is often controlled by transcription factor, a protein that binds to the DNA site at the location where RNAP initiates transcription.

A subtle smile emerged on Dr. James Leidner’s face as he envisioned telling people of the unusual contribution he made to humankind’s mission to Mars.
For 72 straight hours, the study volunteer lay in a bed at UT Southwestern, the monotony broken only at night when researchers placed his lower body in a sealed, vacuum-equipped sleeping bag to pull down body fluids that naturally flowed into his head while supine.
New research published in JAMA Ophthalmology shows that by suctioning these fluids and unloading brain pressure, the specially designed sleeping bag may prevent vision problems astronauts endure in space, where fluids float into the head and continually push and reshape the back of the eyeball.
The phenomenon has vexed scientists for more than a decade and remains one of the biggest health dilemmas of human space exploration. But the findings from UT Southwestern — which NASA enlisted to seek answers to astronauts’ vision problems — suggest the high-tech sacks may provide a solution.
Notably, researchers found that while just three days of lying flat induced enough pressure to slightly alter the eyeball’s shape, no such change occurred when the suction technology was used.
“We don’t know how bad the effects might be on a longer flight, like a two-year Mars operation,” said Benjamin Levine, M.D., a UT Southwestern cardiologist who is helping NASA address the health risks of brain pressure and abnormal blood flow in space. “It would be a disaster if astronauts had such severe impairments that they couldn’t see what they’re doing and it compromised the mission.”
Reshaping eyeballs

A characteristic of depression is a lack of motivation. Cold Spring Harbor Laboratory (CSHL) Professor Bo Li, in collaboration with CSHL Adjunct Professor Z. Josh Huang, discovered a group of neurons in the mouse brain that influences the animal’s motivation to perform tasks for rewards. Dialing up the activity of these neurons makes a mouse work faster or more vigorously — up to a point. These neurons have a feature that prevents the mouse from becoming addicted to the reward. The findings may point to new therapeutic strategies for treating mental illnesses like depression that affect motivation in humans.
The anterior insular cortex is a region of the brain that plays a critical role in motivation. A set of neurons that activate a gene called Fezf2(Fezf2 neurons) in this area are active when mice are doing both physical and cognitive tasks. Li and his lab hypothesized that these neurons do not affect the mouse’s ability to do the task; rather, the brain cells influence the mouse’s motivational drive.
Mice were trained to lick a water bottle spout to receive a small sugar reward. When researchers dialed up the activity of these Fezf2 neurons, mice would lick more vigorously. If the neuron activity was dialed down, the mice would lick more slowly. The researchers saw a similar result in another experiment in which the mice ran on a wheel to receive a reward. The mice ran faster if the Fezf2 neurons were stimulated. The same effect occurred with other tasks.
Li and his team were surprised to discover a feature that prevents the mice from becoming addicted to the tasks and their rewards. When mice drank their fill of sugar water and were satiated, they would not lick or run faster to get more sugar, even if the researchers dialed up the activity of the Fezf2 neurons.
Finding a way to fine-tune the human equivalent of these neurons might help people struggling with motivation due to mental illnesses like depression. Li says, “We want to selectively increase the motivation of the person so that they can do the things that they need to do, but we don’t want to create addictive drugs.”
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Materials provided by Cold Spring Harbor Laboratory. Original written by Luis Sandoval. Note: Content may be edited for style and length.

In an effort to improve treatment for obsessive compulsive disorder, a team of researchers has for the first time recorded electrical signals in the human brain associated with ebbs and flows in OCD symptoms over an extended period in their homes as they went about daily living. The research could be an important step in making an emerging therapy called deep brain stimulation responsive to everyday changes in OCD symptoms.
OCD, which affects as much as 2% of the world’s population, causes recurring unwanted thoughts and repetitive behaviors. The disorder is often debilitating, and up to 20-40% of cases don’t respond to traditional drug or behavioral treatments. Deep brain stimulation, a technique that involves small electrodes precisely placed in the brain that deliver mild electrical pulses, is effective in treating over half of patients for whom other therapies failed. A limitation is that DBS is unable to adjust to moment-to-moment changes in OCD symptom, which are impacted by the physical and social environment . But adaptive DBS — which can adjust the intensity of stimulation in response to real-time signals recorded in the brain — could be more effective than traditional DBS and reduce unwanted side effects.
“OCD is a disorder in which symptom severity is highly variable over time and can be elicited by triggers in the environment,” said David Borton, an associate professor of biomedical engineering at Brown University, a biomedical engineer at the U.S. Department of Veterans Affairs Center for Neurorestoration and Neurotechnology and a senior author of the new research. “A DBS system that can adjust stimulation intensity in response to symptoms may provide more relief and fewer side effects for patients. But in order to enable that technology, we must first identify the biomarkers in the brain associated with OCD symptoms, and that is what we are working to do in this study.”
The research, led by Nicole Provenza, a recent Brown biomedical engineering Ph.D. graduate from Borton’s laboratory, was a collaboration between Borton’s research group, affiliated with Brown’s Carney Institute for Brain Science and School of Engineering; Dr. Wayne Goodman’s and Dr. Sameer Sheth’s research groups at Baylor College of Medicine; and Jeff Cohn from the University of Pittsburgh’s Department of Psychology and Intelligent Systems Program and Carnegie Mellon University.
For the study, Goodman’s team recruited five participants with severe OCD who were eligible for DBS treatment. Sheth, lead neurosurgeon, implanted each participant with an investigational DBS device from Medtronic capable of both delivering stimulation and recording native electrical brain signals. Using the sensing capabilities of the hardware, the team gathered brain-signal data from participants in both clinical settings and at home as they went about daily activities.
Along with the brain signal data, the team also collected a suite of behavioral biomarkers. In the clinical setting, these included facial expression and body movement. Using computer vision and machine learning, they discovered that the behavioral features were associated with changes in internal brain states. At home, they measured participants’ self-reports of OCD symptom intensity as well as biometric data — heart rate and general activity levels — recorded by a smart watch and paired smartphone application provided by Rune Labs. All of those behavioral measures were then time-synched to the brain-sensing data, enabling the researchers to look for correlations between the two.