A new study has shown that gentle streams of water carrying sound and microscopic air bubbles can clean bacteria from salad leaves more effectively than current washing methods used by suppliers and consumers. As well as reducing food poisoning, the findings could reduce food waste and have implications for the growing threat of anti-microbial resistance.
Salad and leafy green vegetables may be contaminated with harmful bacteria during growing, harvesting, preparation and retail leading to outbreaks of food poisoning which may be fatal in vulnerable groups.
Because there is no cooking process to reduce the microbial load in fresh salads, washing is vital by the supplier and the consumer.
Washing with soap, detergent bleach or other disinfectants is not recommended and the crevices in the leaf surface means washing with plain water may leave an infectious dose on the leaf. Even if chemicals are used, they may not penetrate the crevices.
In this new study, published in the journal Ultrasound in Medicine and Biology, scientists used acoustic water streams to clean spinach leaves directly sourced from the field crop, then compared the results with leaves rinsed in plain water at the same velocity.
Professor Timothy Leighton of the University of Southampton, who invented the technology and led this research, explains: “Our streams of water carry microscopic bubbles and acoustic waves down to the leaf. There the sound field sets up echoes at the surface of the leaves, and within the leaf crevices, that attract the bubbles towards the leaf and into the crevices. The sound field also causes the walls of the bubbles to ripple very quickly, turning each bubble into a microscopic ‘scrubbing’ machine. The rippling bubble wall causes strong currents to move in the water around the bubble, and sweep the microbes off the leaf. The bacteria, biofilms, and the bubbles themselves, are then rinsed off the leaf, leaving it clean and free of residues.”
The results showed that the microbial load on samples cleaned with the acoustic streams for two minutes was significantly lower six days after cleaning than on those treated without the added sound and bubbles. The acoustic cleaning also caused no further damage to the leaves and demonstrated the potential to extend food shelf life, which has important economic and sustainability implications.
Improving how food providers clean fresh produce could have a major role to play in combating the threat of anti-microbial resistance. In 2018 and 2019, there were fatal outbreaks of different strains of E. coli on romaine lettuce in the USA and Canada and samples from humans infected showed strains that are resistant to antibiotics.
University of Southampton PhD student Weng Yee (Beverly) Chong, who was part of the research team added: “I am very grateful to Vitacress and EPSRC for funding my PhD. I came from an engineering background, and took Professor Leighton’s classes, but he told me that I could be a trans-disciplinary PhD student, and become a microbiologist whilst increasingmy engineering skills. I am also very grateful to Sloan Water Technology Ltd.: They opened up their laboratories for use by students like me, so that I can keep working on my experiments. It is an exciting environment to work in because they are doing so much inventive work to combat the pandemic and infections as a whole.”
Previously as part of her PhD Beverly has studied how the technology could reduce the infection risk to horses and other livestock through hay cleaning.
The work was sponsored by Vitacress, whose Group Technical Director Helen Brierley said: “Ensuring food safety for our products is an essential requirement. At Vitacress, we wash our produce in natural spring water, and this type of ground-breaking new technology helps to enhance our process whilst ensuring our commitment to protect the environment is maintained. We are always interested in new developments and are excited to see the results of this research.”

Story Source:
Materials provided by University of Southampton. Note: Content may be edited for style and length.

Positive psychological effects associated with taking small doses of psychedelic drugs are likely the result of users’ expectations, suggests a study published today in eLife.
The study — the largest placebo-controlled trial on psychedelics to date — used an innovative ‘self-blinding citizen science’ approach, where members of the public who were already microdosing implemented their own placebo control following online instructions. The results from the trial may influence future studies in real-world settings.
There has been renewed interest in studying whether psychedelic drugs may be a useful treatment for depression, addiction, obsessive-compulsive disorders and other conditions. Few small studies have previously suggested that microdoses — small doses of psychedelic drugs taken one to three times a week — may improve people’s wellbeing, creativity and overall cognitive performance. But many of the studies lack a control group of participants taking a dummy pill to determine if these positive outcomes are the result of the drug’s action, or the result of the participants’ expectations of a benefit — the so-called placebo effect. “Anecdotal reports about the benefits of microdosing are almost certainly biased by the placebo effect,” says lead author Balázs Szigeti, a research associate at Imperial College London, UK.
Szigeti and his colleagues designed a citizen science study where individuals who were already microdosing could participate online. First, the 191 participants followed a setup procedure that mixed placebo pills with microdose ones. After the setup, the participants had a set of capsules without knowing which were placebo and which were microdose. The authors call this process ‘self-blinding’, as participants lost knowledge of which drug they were taking. The setup included barcodes which, when scanned, linked to the study’s IT infrastructure and allowed the researchers to track who had taken microdoses or placebos. The participants then filled out surveys about their experiences and completed online cognitive tests, while they took the pills over a four-week period.
Participants who were taking the real psychoactive drugs and those unknowingly taking the placebos reported similar psychological benefits. “Our results are mixed: on the one hand, we observed microdosing’s benefits in a wide range of psychological measures; on the other hand, equal benefits were seen among participants taking placebos,” Szigeti explains. “These findings suggest that the benefits are not due to the drug, but rather due to the placebo-like expectation effects. Many participants who reported that they experienced positive effects while taking the placebo were shocked to learn after the study that they hadn’t been taking the real drug.”
The authors caution that the results are not as reliable as the results from a traditional placebo-controlled study, due to participants sourcing their drug from the black market. However, the team’s citizen science approach accurately reflects ‘real-life microdosing’ — that is, how microdosing is done in practice. Additionally, the study cost a fraction of what a traditional clinical study would cost, which may make it a useful first step in assessing whether other popular phenomena can be explained by the placebo effect.
“The successful execution of this study could inspire similar studies in a broad range of scientific or medical contexts,” says senior author David Erritzoe, Clinical Senior Lecturer in Psychiatry at Imperial College London. “Accounting for the placebo effect is important when assessing trends such as the use of cannabidiol oils, fad diets or supplements where social pressure or users’ expectations can lead to a strong placebo response. Self-blinding citizen science initiatives could be used as an inexpensive, initial screening tool before launching expensive clinical studies.”

Story Source:
Materials provided by eLife. Note: Content may be edited for style and length.

In a new study from Shiley Eye Institute at UC San Diego Health, researchers have identified a potential new marker that shows cardiovascular disease may be present in a patient using an optical coherence tomography (OCT) scan — a non-invasive diagnostic tool commonly used in ophthalmology and optometry clinics to create images of the retina. The finding suggests it may be possible to detect heart disease during an eye examination.
In the paper published March 2, 2021 in EClinical Medicine by The Lancet, the research team examined lesions of the retina, the inner-most, light-sensitive layer of the eye, to determine if a cardiovascular disorder may be present.
“The eyes are a window into our health, and many diseases can manifest in the eye; cardiovascular disease is no exception,” said lead author Mathieu Bakhoum, MD, PhD, a physician-scientist and retina surgeon at UC San Diego Health. “Ischemia, which is decreased blood flow caused by heart disease, can lead to inadequate blood flow to the eye and may cause cells in the retina to die, leaving behind a permanent mark. We termed this mark ‘retinal ischemic perivascular lesions,’ or RIPLs, and sought to determine if this finding could serve as a biomarker for cardiovascular disease.”
As part of the study, the team reviewed the records of individuals who received a retinal OCT scan at UC San Diego Health from July 2014 to July 2019. From that cohort, two groups were identified after medical chart review: one consisted of 84 individuals with heart disease and the other included 76 healthy individuals as the study’s control group. An increased number of RIPLs was observed in the eyes of individuals with heart disease.
According to the researchers, the higher number of RIPLs in the eye, the higher the risk for cardiovascular disease.
“The only way we can visualize the smallest blood vessels in the body is in the eye. The retina in particular provides important evidence of the adverse effects of cardiovascular issues, such as high blood pressure,” said Anthony DeMaria, MD, Judith and Jack White Chair in Cardiology and cardiologist at UC San Diego Health. “It’s my hope that the presence of RIPLs in the eye will serve as a marker for cardiovascular disease when patients are undergoing assessment of risk factors for heart disease, or when patients are undergoing evaluation for the suspected presence of heart disease.”
DeMaria said detection of RIPLs could result in identification of cardiovascular disease that would enable early therapy and preventative measures, and potentially reduce numbers of heart attacks or strokes.
A person’s risk for cardiovascular disease is determined by the atherosclerotic cardiovascular disease (ASCVD) risk score calculator, the national guideline developed by the American College of Cardiology. The guideline is considered the gold standard for assessing a patient’s 10-year risk of experiencing a cardiovascular event, such as heart attack or stroke. In the study, researchers found a correlation between the number of RIPLs in a patient’s eye and their ASCVD risk score.
“Individuals with low and borderline ASCVD scores had a low number of RIPLs in their eyes, but as the ASCVD risk increased, so did the number of RIPLs,” said Bakhoum.
Ophthalmologists at UC San Diego Health now consider referring patients to a cardiologist if RIPLs are identified during an OCT scan. The research teams hopes this paper and future studies will result in RIPLs becoming a common ophthalmological marker for identifying potential cardiovascular disease, and incorporated into the overall ASCVD risk score.
“Globally, cardiovascular disease is the number one cause of death and unfortunately many people are unaware they may have heart issues,” said Bakhoum. “The key in preventing this is early detection and treatment. It’s our hope that by identifying RIPLs as a marker for cardiovascular disease providers will be able to identify heart issues before a catastrophic event, such as a heart attack or a stroke, occurs.”

Story Source:
Materials provided by University of California – San Diego. Original written by Jeanna Vazquez. Note: Content may be edited for style and length.

Disruptions in the circadian rhythms in lung cells may explain why adults who survived premature birth are often more at risk of severe influenza infections, suggests a study in mice published today in eLife.
Dramatic improvements in the care of infants born prematurely have allowed many more to survive into adulthood. Yet ex-preemies can face several long-term side effects of the life-saving care they received. The study suggests potential new approaches to treating lasting lung problems in those born prematurely.
Many premature infants are not able to breathe on their own and require oxygen to survive. But receiving too much oxygen may cause lasting damage to the lung that makes them more prone to severe flu infection later in life. In a previous study*, senior author and neonatologist Shaon Sengupta, and her colleagues at the Children’s Hospital of Philadelphia Research Institute, Pennsylvania, US, found that susceptibility to flu in mice depended on the time of day when they caught the infection. Mice that caught the infection when they became active at dusk were more likely to die, while those infected as they went to sleep at dawn were more likely to survive. This suggests that the circadian clock, which controls the daytime and nighttime activities of the body, may offer some protection against flu.
“Given these previous findings, we wanted to see if the severity of flu infection in former premature infants may be caused by disruptions to their circadian clock,” says Yasmine Issah, a former Research Technician at the Children’s Hospital of Philadelphia Research Institute, and co-first author of the current study alongside Postdoctoral Research Fellow Amruta Naik.
The team began by showing that the time of day when exposure to flu occurred did not affect susceptibility to infection in adult mice that were exposed to high levels of oxygen as newborns. This suggests that these mice had lost their circadian clock-based flu protection.
But when the team tested the ability of the animals to readjust to a normal day-night schedule after living in dim light for several weeks, they found the animals had no problems — suggesting that their central circadian clock in the brain, which is regulated by exposure to daylight, was working normally.
To find out if the circadian problems were restricted to lung cells, which have their own circadian clocks separate from the brain clock, the team removed a key circadian clock gene called Bmal1 in the lung cells of normal adult mice. They eliminated the gene in the same lung cells that are damaged in newborn mice given high levels of oxygen. As with the mice that had been exposed to high oxygen as newborns, the adult animals with the deleted gene were equally susceptible to flu at dawn or dusk.
“Our findings suggest that adverse early-life exposures can disrupt the lung circadian clock,” concludes Sengupta, an attending neonatologist at the Children’s Hospital of Philadelphia Research Institute. “Those born prematurely are uniquely vulnerable to this faulty development of their circadian network, and this is a new paradigm for understanding the lung problems that persist into adulthood in ex-preemies. These findings could pave the way for potential new treatments that work by improving the circadian health in adults born prematurely.”

Story Source:
Materials provided by eLife. Note: Content may be edited for style and length.

They can hear well up to about forty years old, but then suddenly deafness strikes people with DFNA9. The cells of the inner ear can no longer reverse the damage caused by a genetic defect in their DNA. Researchers at Radboud university medical center have now developed a “genetic patch” for this type of hereditary deafness, with which they can eliminate the problems in the hearing cells. Further research in animals and humans is needed to bring the genetic patch to the clinic as a therapy.
Hereditary deafness can manifest itself in different ways. Often the hereditary defect (mutation) immediately causes deafness from birth. Sometimes, as with DFNA9, you experience the initial problems in hearing after forty, fifty, sixty years. This has everything to do with the way DFNA9 mechanistically works. Every person gets half of his genes from his father and the other half from his mother. If you have two healthy copies of the DFNA9 gene, your inner ear works normal. If you receive a mutated copy of the gene from either your father or mother, deafness will develop later in life.
Protein spaghetti
Erik de Vrieze and Erwin van Wijk, both researchers at Hearing & Genes of the department of Ear, Nose and Throat, have conducted extensive research into the condition. De Vrieze: “We now know that you actually produce enough of the associated DFNA9 protein with just one healthy gene copy to be able to hear well for life. But there is a catch with this condition. The mutated protein is, in a way, disturbing the function of the healthy protein. It sticks to it, so that the healthy protein can also no longer do its job. This clumped protein spaghetti is constantly being removed by the cells of the inner ear, but after decades the clean-up service in these cells is reaching its limit and can no longer cope with these protein clumps. A threshold value is exceeded. As a result, the waste accumulates, the hearing cells start to function poorly and even die over time. After years of normal hearing, DFNA9 patients suddenly notice that their hearing is deteriorating, and sometimes deteriorating very quickly. Until at some point they will become deaf. ”
Enough time for treatment
The specific DFNA9 mutation seems to originate from a common ancestor in the Southern Netherlands, somewhere at the end of the Middle Ages. This can more or less be deduced from the spread of the fairly unique clinical manifestation, which is now estimated to occur in about 1500 people in the (southern) Netherlands and Belgium. Perhaps even more important than the origin of the disease is whether or not anything can be done about it. Van Wijk: “This condition has two favorable characteristics for therapy development. Firstly, it is a hereditary condition that only manifests itself after a few decades in life. In case an effective treatment will become available for this disease, a sufficiently large timeframe is available to apply it before the hearing loss really strikes. ”
Turning off mutant gene

advertisement

The other point — developing an effective therapy — is a bit more complicated, but offers good starting points. Van Wijk: “The idea is that by specifically turning off the mutated gene copy you can prevent deafness. Without this mutated gene copy, no mutant protein will be produced and protein clumping will no longer take place. In addition, one healthy gene copy alone produces enough protein to maintain good hearing. ”
Genetic patch
De Vrieze and Van Wijk further developed this idea. Together with colleagues, they have now published the research results in the scientific journal Molecular Therapy — Nucleic Acids. “Genes, that reside on our DNA, provide the genetic code for the translation process into proteins,” says De Vrieze. “To get from a gene to a protein, you always need a translation process via so-called messenger RNA. And that is exactly the process we focused on. The unique DNA error in the DFNA9 gene is also reflected in the RNA. We developed a small piece of RNA that specifically binds to the messenger RNA derived from the mutated DFNA9 gene. As a result, the entire mutated messenger RNA is targeted for degradation. In this way, an essential link is lost and the mutant DFNA9 protein is no longer or hardly produced. The piece of RNA that we stick on the mutated DFNA9 messenger RNA is named an antisense oligonucleotide or “genetic patch.”
Perspective
In recent years, De Vrieze and Van Wijk have not only developed this genetic patch, but also investigated its effect in cultured cells. Their current article is mainly describing these results, as the approach works in cultured cells. So there is a “proof of concept,” as it is called in science. In short, the research shows that the approach works at the cellular level.
Arthur Robbesom of the “The Ninth of …” DFNA9 Foundation is delighted with the study. “This offers a real perspective for about 1,500 people in the Netherlands and Belgium who are suffering from this condition. “The foundation is also closely involved in this research. Robbesom:” Now it is important to take the next necessary steps in the research as soon as possible. We will wholeheartedly support you.”

Story Source:
Materials provided by Radboud University Medical Center. Note: Content may be edited for style and length.

If you’re looking for an indoor space with a low level of particulate air pollution, a commercial airliner flying at cruising altitude may be your best option. A newly reported study of air quality in indoor spaces such as stores, restaurants, offices, public transportation — and commercial jets — shows aircraft cabins with the lowest levels of tiny aerosol particles.
Conducted in July 2020, the study included monitoring both the number of particles and their total mass across a broad range of indoor locations, including 19 commercial flights in which measurements took place throughout departure and arrival terminals, the boarding process, taxiing, climbing, cruising, descent, and deplaning. The monitoring could not identify the types of the particles and therefore does not provide a direct measure of coronavirus exposure risk.
“We wanted to highlight how important it is to have a high ventilation rate and clean air supply to lower the concentration of particles in indoor spaces,” said Nga Lee (Sally) Ng, associate professor and Tanner Faculty Fellow in the School of Chemical and Biomolecular Engineering and the School of Earth and Atmospheric Sciences at the Georgia Institute of Technology. “The in-flight cabin had the lowest particle mass and particle number concentration.”
The study, believed to be the first to measure both size-resolved particle mass and number in commercial flights from terminal to terminal and a broad range of indoor spaces, has been accepted for publication in the journal Indoor Air and posted online at the journal’s website. Supported by Delta Air Lines, the research may be the first to comprehensively measure particle concentrations likely to be encountered by passengers from terminal to terminal.
As scientists learn more about transmission of the coronavirus, the focus has turned to aerosol particles as an important source of viral spread indoors. Infected people can spread the virus as they breathe, talk, or cough, creating particles ranging in size from less than a micron — one millionth of a meter — to 1,000 microns. The larger particles quickly fall out of the air, but the smaller ones remain suspended.
“Especially in poorly ventilated spaces, these particles can be suspended in the air for a long period of time, and can travel to every corner of a room,” Ng said. “If they are viral particles, they can infect people who may be at a considerable distance from a person emitting the particles.”
To better understand the circulation of airborne particles, Delta approached Ng to conduct a study of multiple indoor environments, with a strong focus on air travel conditions. Using handheld instruments able to measure the total number of particles and their mass, Georgia Tech researchers examined air quality in a series of Atlanta area restaurants, stores, offices, homes, and vehicles — including buses, trains, and private automobiles.

advertisement

They trained Delta staff to conduct the same type of measurements in terminals, boarding areas, and a variety of aircraft through all phases of flight. The Delta staff recorded their locations as they moved through the terminals, and the instruments produced measurements consistent with the restaurants and stores they passed on their way to and from boarding and departure gates.
“The measurements started as soon as they stepped into the departure terminal,” Ng said. “We were thinking about the whole trip, what a person would encounter from terminal to terminal.”
In flight, aircraft air is exchanged between 10 and 30 times per hour. Some aircraft bring in exclusively outside air, which at cruising altitude is largely free of pollutant particles found in air near the ground. Other aircraft mix outdoor air with recirculated air that goes through HEPA filters, which remove more than 99% of particles.
In all, the researchers evaluated measurements from 19 commercial flights with passenger loads of approximately 50%. The flights included a mix of short- and medium-length flights, and aircraft ranging from the CRJ-200 and A220 to the 757, A321, and 737.
Among all the spaces measured, restaurants had the highest particle levels because of cooking being done there. Stores were next, followed by vehicles, homes, and offices. The average sub-micron particle number concentration measured in restaurants, for instance, was 29,400 particles per cubic centimeter, and in offices it was 2,473 per cubic centimeter.

advertisement

“We have quite a comprehensive data set to look at the size distribution of particles across these different spaces,” Ng said. “We can now compare indoor air quality in a variety of different spaces.”
Because of the portable instruments used, the researchers were unable to determine the source of the particles, which could have included both biological and non-biological sources. “Further studies can include direct measurements of viral loads and tracing particle movements in indoor spaces,” she added.
Jonathan Litzenberger, Delta’s managing director of Global Cleanliness Strategy, said the research helps advance the company’s goals of protecting its customers and employees.
“Keeping the air clean and safe during flight is one of the most foundational layers of protection Delta aims to provide to our customers and employees,” he said. “We are always working to better understand the travel environment and confirm that the measures we are implementing are working.”
Overall, the study highlights the importance of improving indoor air quality as a means of reducing coronavirus transmission.
“Regardless of whether you are in an office or an aircraft, having a higher ventilation rate and good particle filtration are the keys to reducing the total particle concentration,” said Ng. “That should also reduce the concentration of any viral particles that may be present.”

Credit: SDI Productions

Doctors can’t reliably predict whether an adult newly diagnosed with COVID-19 will recover quickly or battle life-threatening complications. The same is true for children.

Thankfully, the vast majority of kids with COVID-19 don’t get sick or show only mild flu-like symptoms. But a small percentage develop a delayed, but extremely troubling, syndrome called multisystem inflammatory syndrome in children (MIS-C). This can cause severe inflammation of the heart, lungs, kidneys, brain, and other parts of the body, coming on weeks after recovering from COVID-19. Fortunately, most kids respond to treatment and make rapid recoveries.

COVID-19’s sometimes different effects on kids likely stem not from the severity of the infection itself, but from differences in the immune response or its aftermath. Additional support for this notion comes from a new study, published in the journal Nature Medicine, that compared immune responses among children and adults with COVID-19 [1]. The study shows that the antibody responses in kids and adults with mild COVID-19 are quite similar. However, the complications seen in kids with MIS-C and adults with severe COVID-19 appear to be driven by two distinctly different types of antibodies involved in different aspects of the immune response.

The new findings come from pediatric pulmonologist Lael Yonker, Massachusetts General Hospital (MGH) Cystic Fibrosis Center, Boston, and immunologist Galit Alter, the Ragon Institute of MGH, Massachusetts Institute of Technology, and Harvard, Cambridge. Yonker runs a biorepository that collects samples from kids with cystic fibrosis. When the pandemic began, she started collecting plasma samples from children with mild COVID-19. Then, when Yonker and others began to see children hospitalized with MIS-C, she collected some plasma samples from them, too.

Using these plasma samples as windows into a child’s immune response, the research teams of Yonker and Alter detailed antibodies generated in 17 kids with MIS-C and 25 kids with mild COVID-19. They also profiled antibody responses of 60 adults with COVID-19, including 26 with severe disease.

Comparing antibody profiles among the four different groups, the researchers had expected children’s antibody responses to look quite different from those in adults. But they were in for a surprise. Adults and kids with mild COVID-19 showed no notable differences in their antibody profiles. The differences only came into focus when they compared antibodies in kids with MIS-C to adults with severe COVID-19.

In kids who develop MIS-C after COVID-19, they saw high levels of long-lasting immunoglobulin G (IgG) antibodies, which normally help to control an acute infection. Those high levels of IgG antibodies weren’t seen in adults or in kids with mild COVID-19. The findings suggest that in kids with MIS-C, those antibodies may activate scavenging immune cells, called macrophages, to drive inflammation and more severe illness.

In adults with severe COVID-19, the pattern differed. Instead of high levels of IgG antibodies, adults showed increased levels of another type of antibody, called immunoglobulin A (IgA). These IgA antibodies apparently were interacting with immune cells called neutrophils, which in turn led to the release of cytokines. That’s notable because the release of too many cytokines can cause what’s known as a “cytokine storm,” a severe symptom of COVID-19 that’s associated with respiratory distress syndrome, multiple organ failure, and other life-threatening complications.

To understand how a single virus can cause such different outcomes, studies like this one help to tease out their underlying immune mechanisms. While more study is needed to understand the immune response over time in both kids and adults, the hope is that these findings and others will help put us on the right path to discover better ways to help protect people of all ages from the most severe complications of COVID-19.

Reference:

[1] Humoral signatures of protective and pathological SARS-CoV-2 infection in children. Bartsch YC, Wang C, Zohar T, Fischinger S, Atyeo C, Burke JS, Kang J, Edlow AG, Fasano A, Baden LR, Nilles EJ, Woolley AE, Karlson EW, Hopke AR, Irimia D, Fischer ES, Ryan ET, Charles RC, Julg BD, Lauffenburger DA, Yonker LM, Alter G. Nat Med. 2021 Feb 12.

Links:

COVID-19 Research (NIH)

“NIH effort seeks to understand MIS-C, range of SARS-CoV-2 effects on children,” NIH news release, March 2, 2021.

Lael Yonker (Massachusetts General Hospital, Boston)

Alter Lab (Ragon Institute of Massachusetts General Hospital, MIT, and Harvard, Cambridge)

NIH Support: National Institute of Allergy and Infectious Diseases; National Cancer Institute

A large proportion of the benefit that a person gets from taking a real drug or receiving a treatment to alleviate pain is due to an individual’s mindset, not to the drug itself. Understanding the neural mechanisms driving this placebo effect has been a longstanding question. A meta-analysis published in Nature Communications finds that placebo treatments to reduce pain, known as placebo analgesia, reduce pain-related activity in multiple areas of the brain.
Previous studies of this kind have relied on small-scale studies, so until now, researchers did not know if the neural mechanisms underlying placebo effects observed to date would hold up across larger samples. This study represents the first large-scale mega-analysis, which looks at individual participants’ whole brain images. It enabled researchers to look at parts of the brain that they did not have sufficient resolution to look at in the past. The analysis was comprised of 20 neuroimaging studies with 600 healthy participants. The results provide new insight on the size, localization, significance and heterogeneity of placebo effects on pain-related brain activity.
The research reflects the work of an international collaborative effort by the Placebo Neuroimaging Consortium, led by Tor Wager , the Diana L. Taylor Distinguished Professor in Neuroscience at Dartmouth and Ulrike Bingel, a professor at the Center for Translational Neuro- and Behavioral Sciences in the department of neurology at University Hospital Essen, for which Matthias Zunhammer and Tamás Spisák at the University Hospital Essen, served as co-authors. The meta-analysis is the second with this sample and builds on the team’s earlier research using an established pain marker developed earlier by Wager’s lab.
“Our findings demonstrate that the participants who showed the most pain reduction with the placebo also showed the largest reductions in brain areas associated with pain construction,” explains co-author Wager, who is also the principal investigator of the Cognitive and Affective Neuroscience Lab at Dartmouth. “We are still learning how the brain constructs pain experiences, but we know it’s a mix of brain areas that process input from the body and those involved in motivation and decision-making. Placebo treatment reduced activity in areas involved in early pain signaling from the body, as well as motivational circuits not tied specifically to pain.”
Across the studies in the meta-analysis, participants had indicated that they felt less pain; however, the team wanted to find out if the brain responded to the placebo in a meaningful way. Is the placebo changing the way a person constructs the experience of pain or is it changing the way a person thinks about it after the fact? Is the person really feeling less pain?
With the large sample, the researchers were able to confidently localize placebo effects to specific zones of the brain, including the thalamus and the basal ganglia. The thalamus serves as a gateway for sights and sounds and all kinds of sensory motor input. It has lots of different nuclei, which act like processing stations for different kinds of sensory input. The results showed that parts of the thalamus that are most important for pain sensation were most strongly affected by the placebo. In addition, parts of the somatosensory cortex that are integral to the early processing of painful experiences were also affected. The placebo effect also impacted the basal ganglia, which are important for motivation and connecting pain and other experiences to action. “The placebo can affect what you do with the pain and how it motivates you, which could be a larger part of what’s happening here,” says Wager. “It’s changing the circuitry that’s important for motivation.”
The findings revealed that placebo treatments reduce activity in the posterior insula, which is one of the areas that are involved in early construction of the pain experience. This is the only site in the cortex that you can stimulate and invoke the sense of pain. The major ascending pain pathway goes from parts of the thalamus to the posterior insula. The results provide evidence that the placebo affects that pathway for how pain is constructed.
Prior research has illustrated that with placebo effects, the prefrontal cortex is activated in anticipation of pain. The prefrontal cortex helps keep track of the context of the pain and maintain the belief that it exists. When the prefrontal cortex is activated, there are pathways that trigger opioid release in the midbrain that can block pain and pathways that can modify pain signaling and construction.
The team found that activation of the prefrontal cortex is heterogeneous across studies, meaning that no particular areas in this region were activated consistently or strongly across the studies. These differences across studies are similar to what is found in other areas of self-regulation, where different types of thoughts and mindsets can have different effects. For example, other work in Wager’s laboratory has found that rethinking pain by using imagery and storytelling typically activates the prefrontal cortex, but mindful acceptance does not. Placebo effects likely involve a mix of these types of processes, depending on the specifics of how it is given and people’s predispositions.
“Our results suggest that placebo effects are not restricted solely to either sensory/nociceptive or cognitive/affective processes, but likely involves a combination of mechanisms that may differ depending on the placebo paradigm and other individual factors,” explains Bingel. “The study’s findings will also contribute to future research in the development of brain biomarkers that predict an individual’s responsiveness to placebo and help distinguish placebo from analgesic drug responses, which is a key goal of the new collaborative research center, Treatment Expectation .”
Understanding the neural systems that utilize and moderate placebo responses has important implications for clinical care and drug-development. The placebo responses could be utilized in a context-, patient-, and disease-specific manner. The placebo effect could also be leveraged alongside a drug, surgery, or other treatment, as it could potentially enhance patient outcomes.

Story Source:
Materials provided by Dartmouth College. Original written by Amy D. Olson. Note: Content may be edited for style and length.