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To create high-resolution, 3D images of tissues such as the brain, researchers often use two-photon microscopy, which involves aiming a high-intensity laser at the specimen to induce fluorescence excitation. However, scanning deep within the brain can be difficult because light scatters off of tissues as it goes deeper, making images blurry.
Two-photon imaging is also time-consuming, as it usually requires scanning individual pixels one at a time. A team of MIT and Harvard University researchers has now developed a modified version of two-photon imaging that can image deeper within tissue and perform the imaging much more quickly than what was previously possible.
This kind of imaging could allow scientists to more rapidly obtain high-resolution images of structures such as blood vessels and individual neurons within the brain, the researchers say.
“By modifying the laser beam coming into the tissue, we showed that we can go deeper and we can do finer imaging than the previous techniques,” says Murat Yildirim, an MIT research scientist and one of the authors of the new study.
MIT graduate student Cheng Zheng and former postdoc Jong Kang Park are the lead authors of the paper, which appears today in Science Advances. Dushan N. Wadduwage, a former MIT postdoc who is now a John Harvard Distinguished Science Fellow in Imaging at the Center for Advanced Imaging at Harvard University, is the paper’s senior author. Other authors include Josiah Boivin, an MIT postdoc; Yi Xue, a former MIT graduate student; Mriganka Sur, the Newton Professor of Neuroscience at MIT; and Peter So, an MIT professor of mechanical engineering and of biological engineering.
Deep imaging
Two-photon microscopy works by shining an intense beam of near-infrared light onto a single point within a sample, inducing simultaneous absorption of two photons at the focal point, where the intensity is the highest. This long-wavelength, low-energy light can penetrate deeper into tissue without damaging it, allowing for imaging below the surface.

Data from nine cities in Mexico confirms that identifying dengue fever “hot spots” can provide a predictive map for future outbreaks of Zika and chikungunya. All three of these viral diseases are spread by the Aedes aegypti mosquito.
The Lancet Planetary Health published the research, led by Gonzalo Vazquez-Prokopec, associate professor in Emory University’s Department of Environmental Sciences. The study provides a risk-stratification method to more effectively guide the control of diseases spread by Aedes aegypti.
“Our results can help public health officials to do targeted, proactive interventions for emerging Aedes-borne diseases,” Vazquez-Prokopec says. “We’re providing them with statistical frameworks in the form of maps to guide their actions.”
The study encompassed data for 2008 through 2020 from cities in southern Mexico with a high burden of dengue fever cases during that period, along with cases of the more recently emerged diseases of Zika and chikungunya. The cities included Acapulco, Merida, Veracruz, Cancun, Tapachula, Villahermosa, Campeche, Iguala and Coatzacoalcos.
The results found a 62 percent overlap of hot spots for dengue and Zika and 53 percent overlap for cases of dengue and chikungunya. In addition, dengue hot spots between 2008 and 2016 were significantly associated with dengue hotspots detected between 2017 and 2020 in five of the nine cities.
The work builds on a previous study of the spatial-temporal overlap of the three diseases, focused on Merida, a city of one million located in the Yucatan Peninsula. That study showed that nearly half of Merida’s dengue cases from 2008 to 2015 were clustered in 27 percent of the city. These dengue hot spots contained 75 percent of the first chikungunya cases reported during the outbreak of that disease in 2015 and 100 percent of the first Zika cases reported during the Zika outbreak of 2016.

Colorado researchers have published new findings in Emerging Infectious Diseases that take a first look at the use of SARS-CoV-2 mathematical modeling to inform early statewide policies enacted to reduce the spread of the Coronavirus pandemic in Colorado. Among other findings, the authors estimate that 97 percent of potential hospitalizations across the state in the early months of the pandemic were avoided as a result of social distancing and other transmission-reducing activities such as mask wearing and social isolation of symptomatic individuals.
The modeling team was led by faculty and researchers in the Colorado School of Public Health and involved experts from the University of Colorado Anschutz Medical Campus, University of Colorado Denver, University of Colorado Boulder, and Colorado State University.
“One of the defining characteristics of the COVID-19 pandemic was the need for rapid response in the face of imperfect and incomplete information,” said the authors. “Mathematical models of infectious disease transmission can be used in real-time to estimate parameters, such as the effective reproductive number (Re) and the efficacy of current and future intervention measures, and to provide time-sensitive data to policymakers.”
The new paper describes the development of such a model, in close collaboration with the Colorado Department of Health and Environment and the Colorado Governor’s office to gage the impact of early policies to decrease social contacts and, later, the impact of gradual relaxation of Stay-at-Home orders. The authors note that preparing for hospital intensive care unit (ICU) loads or capacity limits was a critical decision-making issue.
The Colorado COVID-19 Modeling team developed a susceptible-exposed-infected-recovered (SEIR) model calibrated to Colorado COVID-19 case and hospitalization data to estimate changes in the contact rate and the Re after emergence of SARS-CoV-2 and the implementation of statewide COVID-19 control policies in Colorado. The modeling team supplemented model estimates with an analysis of mobility by using mobile device location data. Estimates were generated in near real time, at multiple time-points, with a rapidly evolving understanding of SARS-CoV-2. At each time point, the authors generated projections of the possible course of the outbreak under an array of intervention scenarios. Findings were regularly provided to key Colorado decision-makers.
“Real-time estimation of contact reduction enabled us to respond to urgent requests to actively inform rapidly changing public health policy amidst a pandemic. In early stages, the urgent need was to flatten the curve,” note the authors. “Once infections began to decrease, there was interest in the degree of increased social contact that could be tolerated as the economy reopened without leading to overwhelmed hospitals.”
“Although our analysis is specific to Colorado, our experience highlights the need for locally calibrated transmission models to inform public health preparedness and policymaking, along with ongoing analyses of the impact of policies to slow the spread of SARS-CoV-2,” said Andrea Buchwald, PhD, lead author from the Colorado School of Public Health at CU Anschutz. “We present this material not as a final estimate of the impact of social distancing policies, but to illustrate how models can be constructed and adapted in real-time to inform critical policy questions.”
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Materials provided by University of Colorado Anschutz Medical Campus. Original written by Tonya Ewers. Note: Content may be edited for style and length.

Some deaths were not counted as part of prison virus tallies because hospitalized inmates were officially released from custody before they died.Richard Williamson, 86, was rushed from a Florida jail to a hospital last July. Within two weeks, he had died of Covid-19.Hours after Cameron Melius, 26, was released from a Virginia jail in October, he was taken by ambulance to a hospital, where he died. The coronavirus, the authorities said, was a contributing factor.And in New York City, Juan Cruz, 57, who fell ill with Covid-19 while in jail, was moved from a hospital’s jail ward into its regular unit before dying.None of these deaths have been included in official Covid-19 mortality tolls of the jails where the men had been detained. And these cases are not unique. The New York Times identified dozens of people around the country who died under similar circumstances but were not included in official counts.In some cases, in places including Texas, Ohio and California, deaths were added to facilities’ virus tolls after The Times brought missing names to the attention of officials. In other cases, people who were infected with the coronavirus while incarcerated — but granted legal releases because of the severity of their illnesses — were not included in the death tallies of the jails where they got sick. Still other inmates’ deaths were left off facilities’ virus tolls for reasons that are unexplained.More than 2,700 people are reported to have died of Covid-19 in connection to U.S. prisons, jails and immigration detention centers, but the additional cases raise the prospect that the known toll on incarcerated people falls far short of providing the full picture.Family members of inmates held a rally outside of the Department of Corrections in Draper, Utah, in October.Steve Griffin/The Deseret News, via Associated PressConcerns about how coronavirus deaths are documented have emerged throughout the pandemic, including a finding that the toll among nursing home residents in New York State was far higher than known because thousands who died in hospitals had not been included.A surge in deaths across the country last year that went beyond the known Covid-19 toll has health experts suggesting that some virus cases went undiagnosed or were misattributed to other causes. There have also been inconsistencies and shifting guidance regarding which deaths should count as coronavirus deaths.Public health officials say the prospect of overlooked virus deaths tied to the nation’s prisons, jails and immigration detention centers carries particular risks. It is challenging, the experts say, to prepare prisons for future epidemics without knowing the full toll. For now, the publicly known death totals connected to incarceration largely come from the facilities themselves.“You can’t make good public policy if you don’t know what’s actually going on on the ground,” said Sharon Dolovich, director of the Covid Behind Bars Data Project at the University of California, Los Angeles, which tracks coronavirus deaths in American prisons.Prison and jail officials defended their methodologies for tallying coronavirus deaths of incarcerated people, saying they followed all federal and local documentation requirements. Some noted that their task was the tracking of “in custody” deaths, and suggested that including the deaths of people who had recently been in their care — but no longer were — would be both complex and impractical, and might even wind up overstating the number of virus cases with ties to the facilities.“It is unfair to expect jails to somehow take ownership of what happens to people once they are released from our custody,” said Kathy Hieatt, a spokeswoman for the Virginia Beach Sheriff’s Office, which held Mr. Melius in custody. “We follow the law and the extensive standards set by the Virginia Department of Corrections, which include the investigating and reporting of anyone who dies while in custody. Neither require reporting of deaths of former inmates.” She added: “It is asinine to think that we could somehow keep tabs on those thousands of people and take responsibility for them.”Throughout the pandemic, prison systems have used disparate methods to publicly report deaths connected to Covid-19. Nevada’s prisons say they inform state heath officials of inmate Covid-19 deaths but do not make them public. Mississippi prison authorities said no inmates had died from the coronavirus in their facilities before announcing in January that nearly two dozen prisoner deaths were tied to Covid-19.And in Texas, a prison medical committee is re-examining each case in which a medical examiner said Covid-19 was among the causes of death, and has sometimes overruled the earlier findings, according to Jeremy Desel, a spokesman for the state prison system. Shelia Bradley, a 53-year-old prisoner, was found by a medical examiner to have died of “bacterial and possibly fungal pneumonia, a complication of Covid-19,” but the committee concluded that she died from “acute bacterial bronchopneumonia,” without listing Covid-19.Juan Cruz Jr. and Ms. Cruz near a memorial for Mr. Cruz at their home.Amr Alfiky/The New York TimesIn at least nine cases identified by The Times, inmate deaths were not included in facilities’ coronavirus tolls even though medical examiners had cited Covid-19 as a cause or a contributing factor. It was uncertain why they were not included in the prison counts.The Centers for Disease Control and Prevention has recommended that any fatality in which Covid-19 is listed as “a contributing cause” on the death certificate be deemed a coronavirus death even if other causes also are noted, but state and local officials have sometimes taken varying approaches. Further complicating matters, there can be discrepancies between what medical examiners deem the cause of a death and what is listed on death certificates, which are not publicly available in most cases.In another dozen cases identified by The Times, officials say fatalities were not included in tallies of prisoners who died of the virus because the inmates had been formally released from custody before they died. Some of the deaths have been reported by other publications, including North Carolina Health News and The City in New York.Mr. Melius, who worked in a vape shop, died two days after he finished his sentence at a jail in Virginia Beach, where he had been arrested on charges of misdemeanor assault and a probation violation.Covid-19 had spread through the jail, and Mr. Melius’s mother, Tammy Porter, said he fell seriously ill about four hours after he was released. At a hospital that afternoon, he tested positive for the coronavirus and was placed on a ventilator.Ms. Hieatt, the Virginia Beach Sheriff’s Office spokeswoman, said Mr. Melius’s death was not counted in the jail’s toll because he was no longer in custody when he died, nor had he complained of illness while in jail. She suggested that drug use may have played a role in his death, noting that an autopsy found fentanyl in Mr. Melius’s system.A medical examiner concluded that Mr. Melius’s death was as a result of “anoxic encephalopathy following cardiac arrest, in addition to Covid-19 respiratory infection.”Anoxic encephalopathy, a lack of oxygen to the brain, can be caused by a variety of factors, experts said, including cardiac arrest or a drug overdose. A summary of the medical examiner’s autopsy report included no mention of drugs, and a spokeswoman for the medical examiner declined to comment beyond the summary. Complete autopsy reports are not part of the public record in Virginia, nor are death certificates.Cameron Melius was taken by ambulance to a hospital hours after he was released from the Virginia Beach Correctional Center. L. Todd Spencer/The Virginian-Pilot, via Associated PressIn New York City, Juan Cruz had been awaiting trial in jail for two years when he died of Covid-19 in June 2020.On May 1, 2020, Mr. Cruz, who had pleaded not guilty on a sexual assault charge, tested positive for the virus while he was in the Rikers Island jail complex, court records show. Within days, he was transferred to the jail ward of Bellevue Hospital and shackled to his bed frame. On May 12, he was placed on a ventilator, court records show.Mr. Cruz’s lawyers eventually convinced officials to release Mr. Cruz because of the severity of his illness. His handcuffs were removed, and he was taken to a different wing of the hospital. He died there of Covid-19 three weeks later.Jail authorities in New York City say they have not counted the death of Mr. Cruz among its Covid-19 fatalities because Mr. Cruz was not in custody when he died.After The Times raised Mr. Cruz’s circumstances with New York officials, along with several other deaths not included in jail counts, a spokesman for Mayor Bill de Blasio said the administration would be more straightforward about disclosing Covid-19 deaths like Mr. Cruz’s in the future.In Marion County, Fla., Mr. Williamson, who was awaiting trial on charges of sexual battery on a child, had struggled with ailments long before he got the virus. He had suffered three strokes, had congestive heart failure and was nearly blind, said Chris Williamson, his son.By July 2020, after nine months in jail, Mr. Williamson had been hospitalized for Covid-19 and was on a ventilator, his son said. When his condition further deteriorated, prosecutors dropped the charges — officially releasing him from custody — because they knew he was unlikely to survive.Mr. Williamson died in the hospital a few weeks later, and was not included in the county jail’s Covid-19 toll.“It’s kind of that gray area,” Mr. Williamson’s son said, “where they can legitimately say that they’ve had no Covid-19 deaths because maybe no one’s actually died inside of the jail with Covid-19 — because they sent him to the hospital to die.”Reporting was contributed by

Dutch-French research shows that Optical Genome Mapping (OGM) detects abnormalities in chromosomes and DNA very quickly, effectively and accurately. Sometimes even better than all existing techniques together, as they describe in two proof-of-concept studies published in the American Journal of Human Genetics. This new technique could radically change the existing workflow within cytogenetic laboratories.
Human hereditary material is stored in 46 chromosomes (23 pairs). Although those chromosomes are quite stable, changes in number or structure can still occur. A well-known example is Down syndrome, which is caused by an extra chromosome 21 (trisomy 21). An extra chromosome makes a big difference and is quite easy to visualize. But all kinds of other, smaller changes can occur as well in chromosomes. Sometimes pieces of DNA are lost (deletions), sometimes a piece is just repeated (duplication) or it is moved to another place (translocation). An existing piece can also be turned over (inversion) and sometimes new pieces are inserted (insertions). All these structural abnormalities in the chromosomes can cause disease, either congenital genetic diseases, which are present from birth, similar to Down syndrome, or acquired disorders, when the change occurs in a few cells during life which can lead to cancer, such as in leukemia.
Optical Genome Mapping
Cytogenetics is the genetic discipline that examines chromosomes for such abnormalities. To visualize both the large and small changes, several complementary techniques are needed, such as FISH, karyotyping and Copy Number Variant (CNV) microarrays. These are often laborious techniques that individually can only visualize a part of the above-mentioned abnormalities. Recently a new technique has become available — Optical Genome Mapping — which more or less brings together the previous techniques. But new techniques must prove themselves in practice. At Radboud University Medical Center (Radboudumc), Alexander Hoischen, associate professor of Genomics Technologies and Immuno-Genomics, researches new techniques for usability in clinical research and possibly later in patient care. It requires close cooperation between Radboudumc and the industry involved in building latest genomic technologies, in this case the America-based company Bionano Genomics.
Two advantages
Hoischen immediately mentions two major advantages of OGM: “We can now look at extremely long stretches of DNA, so there’s fewer pieces needed to map the entire chromosome. It’s faster and produces fewer errors. Furthermore, unlike the other techniques, we do not have to pre-process or manipulate the DNA, so we look at the real, ‘natural’ DNA. In short: what you see is what you get.”
Automatic, objective, digital

A new screening method that can test the effectiveness of therapeutic molecules designed to ‘glue’ proteins together in the body has been developed by researchers at the University of Birmingham and the University of Leicester.
The research paves the way for drug developers to screen large numbers of potential new drug compounds to discover new treatments for diseases such as breast cancer and Parkinson’s disease.
The ways in which proteins interact with each other are fundamental to all cell functions. These interactions underpin every function of a healthy body, with any slight change in these interactions resulting in disease.
A handful of drugs have been designed that can break apart these interactions, and this serves to disrupt the progress of the disease. However, in some diseases, the problem is caused by protein interactions not happening, or not happening in the right way. So new drugs that work by ‘gluing’ these proteins together would be highly effective, but finding them is not straightforward.
In this study, Chemical Science, researchers in the University of Birmingham’s School of Biosciences have designed a system that uses mass spectrometry to measure the precise mass of a pair of proteins, plus the ‘glue’, to identify which ‘glue’ is the strongest and thus will likely be the most successful in treating the disease.
Lead author Dr Aneika Leney said: “A healthy body depends very much on the cells’ proteins being able to signal effectively. Any wrong signal can lead to disease and that could be the wrong proteins sticking together — or proteins not joining up as they should. We want a drug that corrects for this. Our methods provides a ‘snapshot’ of what is happening to the proteins when we add a potential drug so we can see quickly whether the ‘glue’ is working”
The team worked with chemical biologists at the University of Leicester to test the method on therapeutic compounds being studied by co-lead author Dr Richard Doveston and his team.
Dr Doveston says: Looking for molecules that act as glues is not easy because things are complicated by having two proteins in the mix. At the early stage of development we often just want to find molecules that are good starting points for development, so they might not be that good as glues at this stage. The current high-throughput screening methods available to us are usually not very effective in this context. The mass spectrometry method is great because we can learn so much from the data and it can be gathered relatively easily and quickly.
Because the glue compounds are highly specific to the identified proteins, interactions with other proteins are rare, so the therapy is unlikely to produce any unlooked-for effects.”
Dr Leney adds: “We hope our approach will be taken up by pharmaceutical companies and used to rapidly screen and test promising drug compounds that can bind proteins together to deliver a therapeutic benefit.”
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Our cells fight microbial invaders by engulfing them into membrane sacs — hostile environments in which pathogens are rapidly destroyed. However, the pathogen Salmonella enterica, which grows and reproduces inside our cells, has evolved ways to detoxify such hostile compartments, turning them into a comfortable home where Salmonella can survive and thrive.
A team of scientists led by EMBL group leader Nassos Typas has uncovered new details of Salmonella´s survival strategies. The researchers analysed protein interactions in Salmonella-infected cells to identify the diverse biological processes of the host cell that the bacterium uses. Salmonella targets and modifies cellular protein machineries and pathways, in which multiple proteins work together, with the help of so-called effector proteins, which it injects into host cells. Altogether, Salmonella is known to release more than 30 effector proteins into infected cells to hijack nutrients and protect itself. However, the functions of many of these proteins, and which host cell proteins they interact with, are largely unknown.
To find these enigmatic protein interactions, the EMBL scientists genetically engineered 32 Salmonella strains by adding identification tags to individual Salmonella proteins — earmarking one protein in each bacterial strain. The identification tags act like a handle the scientists can grab in their experiments. This approach of modifying the effector proteins directly in their host is a breakthrough. It enables researchers to capture the bacterial proteins after they have been secreted into infected cells, and to pull them out along with any host cell proteins that are bound to them. These interacting proteins are then identified using a technique called mass spectrometry.
“The new approach has many benefits over previous experimental strategies. In particular, it characterises the whole set of host-pathogen protein-protein interactions in cells infected with a live pathogen, closely resembling what occurs in a host organism upon Salmonella infection,”says Joel Selkrig, a scientist in the Typas group and one of the two lead authors of the study.
Using their novel approach, the EMBL scientists identified 421 previously unknown interactions between Salmonella proteins and host cell proteins — along with 25 interactions that had been described before.
“We found that multiple Salmonella effectors physically interact with several proteins that the host cell uses to transport cholesterol. This way, cholesterol trafficking can be hijacked for Salmonella´s own purposes,” says Philipp Walch, who recently completed his PhD at EMBL Heidelberg and shares first authorship of the study with Joel.
Cholesterol is an essential component of the biological membranes that surround our cells and the structures within them. Salmonella uses cholesterol to modify the composition of the membrane sacs that surround it, potentially making the membrane more rigid and reinforcing the barrier that separates Salmonella from cellular detection and defence systems, which are present in the host cell´s cytoplasm.
The scientists also found new clues to how two other survival strategies work. One of these strategies is to remodel the network of protein fibres that are used to transport material within the cell. Another strategy involves interfering with the function of a host cell protein that mediates contacts between membranes to facilitate the exchange of lipids and small molecules. Both strategies may help Salmonella to strengthen its protective membrane shield and avoid detection by the host cell´s defence systems.
The recent results follow research published by the Typas group in 2020, in which the researchers described how Salmonella infection can lead to an inflammatory form of cell death. The current study involved scientists from EMBL and colleagues from Imperial College London, UK; the Helmholtz Centre for Infection Research in Braunschweig, Germany; and Rocky Mountain Laboratories in Hamilton, Montana, USA — part of the National Institute of Allergy and Infectious Diseases.
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Scientists at the University of Cambridge have identified rare genetic variants — carried by one in 3,000 people — that have a larger impact on the risk of developing type 2 diabetes than any previously identified genetic effect.
Type 2 diabetes is thought to be driven in part by inherited genetic factors, but many of these genes are yet unknown. Previous large-scale studies have depended on efficient ‘array genotyping’ methods to measure genetic variations across the whole genome. This approach typically does a good job at capturing the common genetic differences between people, though individually these each confer only small increases in diabetes risk.
Recent technical advances have allowed more comprehensive genetic measurement by reading the complete DNA sequences of over 20,000 genes that code for proteins in humans. Proteins are essential molecules that enable our bodies to function. In particular, this new approach has allowed for the first time a large-scale approach to study the impact of rare genetic variants on several diseases, including type 2 diabetes.
By looking at data from more than 200,000 adults in the UK Biobank study, researchers from the Medical Research Council (MRC) Epidemiology Unit at the University of Cambridge used this approach to identify genetic variants associated with the loss of the Y chromosome. This is a known biomarker of biological ageing that occurs in a small proportion of circulating white blood cells in men and indicates a weakening in the body’s cellular repair systems. This biomarker has been previously linked to age-related diseases such as type 2 diabetes and cancer.
In results published today in Nature Communications, the researchers identified rare variants in the gene GIGYF1 that substantially increase susceptibility to loss of the Y chromosome, and also increase an individual’s risk of developing type 2 diabetes six-fold. In contrast, common variants associated with type 2 diabetes confer much more modest increases in risk, typically much lower than two-fold.
Around 1 in 3,000 individuals carries such a GIGYF1 genetic variant. Their risk of developing type 2 diabetes is around 30%, compared to around 5% in the wider population. In addition, people who carried these variants had other signs of more widespread ageing, including weaker muscle strength and more body fat.
GIGYF1 is thought to control insulin and cell growth factor signalling. The researchers say their findings identify this as a potential target for future studies to understand the common links between metabolic and cellular ageing, and to inform future treatments.
Dr John Perry, from the MRC Epidemiology Unit and a senior author on the paper, said: “Reading an individual’s DNA is a powerful way of identifying genetic variants that increase our risk of developing certain diseases. For complex diseases such as type 2 diabetes, many variants play a role, but often only increasing our risk by a tiny amount. This particular variant, while rare, has a big impact on an individual’s risk.”
Professor Nick Wareham, Director of the MRC Epidemiology Unit, added: “Our findings highlight the exciting scientific potential of sequencing the genomes of very large numbers of people. We are confident that this approach will bring a rich new era of informative genetic discoveries that will help us better understand common diseases such as type 2 diabetes. By doing this, we can potentially offer better ways to treat — or even to prevent — the condition.”
Ongoing research will aim to understand how the loss of function variants in GIGYF1 lead to such a substantial increase in the risk of developing type 2 diabetes. Their future research will also examine other links between biomarkers of biological ageing in adults and metabolic disorders.
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Materials provided by University of Cambridge. The original story is licensed under a Creative Commons License. Note: Content may be edited for style and length.

Tourette syndrome, a neurodevelopmental disorder, causes motor and phonic “tics” or uncontrollable repeated behaviors and vocalizations. People affected by Tourette syndrome can often suppress these tics for some time before the urges become overwhelming, and researchers have long wondered at the neural underpinnings of the suppression effort.
Now, in a new study using a non-invasive technique to measure brain activity called high-density electroencephalography (hdEEG), researchers at Yale School of Medicine have assessed the impact of tic suppression on functional connectivity between brain regions.
The study appears in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, published by Elsevier.
“Tic suppression is an important feature of Tourette syndrome. Understanding how someone may temporarily gain control over their tics may inform several research areas in Tourette syndrome. Yet, brain correlates of tic suppression have not been studied extensively, especially in children,” said Denis Sukhodolsky, PhD, senior author of the study, and Associate Professor at the Yale Child Study Center at the Yale School of Medicine, New Haven, CT, USA.
Cameron Carter, MD, Editor of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, said of the study, “Understanding brain mechanisms associated with successful coping in disorders such as Tourette syndrome opens up opportunities for developing targeted treatments to enhance the innate self-control that normally emerges as the brain matures.”
The team led by Dr. Sukhodolsky recorded the brain activity of 72 children, aged 8 to 16 years old, with Tourette syndrome using hdEEG, while they were ticcing freely and while they were suppressing their tics. The researchers then assessed connectivity between the different regions in the brain.
The authors found that connectivity between multiple brain regions was increased while children suppressed their tics. “Some of these regions are part of the default mode network, an array of brain regions engaged during internal thought processes such as daydreaming,” explained first author Simon Morand-Beaulieu, PhD.
Additionally, the researchers reported that functional brain connectivity during tic suppression was positively correlated with age, suggesting that the brain networks of tic suppression undergo developmental changes in response to the experience of tics. “This increase in functional connectivity as children mature is consistent with increasing tic suppression capacities developing into adolescence as well as a better awareness of the sensory phenomena accompanying tics,” said Dr. Morand-Beaulieu.
The study highlights the brain mechanism involved in a temporary decrease in tic frequency, which could have therapeutic implications. “It will be important to assess whether the same mechanism plays a role in a more structured intervention to decrease tic severity, such as behavioral therapy for Tourette syndrome,” said Dr. Sukhodolsky.
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In a new study on mice, Johns Hopkins Medicine researchers report that using MRI scans to measure blood volume in the brain can serve as a noninvasive way to potentially track the progress of gene editing therapies for early-stage Huntington’s disease, a neurodegenerative disorder that attacks brain cells. The researchers say that by identifying and treating the mutation known to cause Huntington’s disease with this type of gene therapy, before a patient starts showing symptoms, it may slow progression of the disease.
The findings of the study were published May 27 in the journal Brain.
“What’s exciting about this study is the opportunity to identify a reliable biomarker that can track the potential success of genetic therapies before patients start manifesting symptoms,” says Wenzhen Duan, M.D., Ph.D., director of the translational neurobiology laboratory and professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. “Such a biomarker could facilitate the development of new treatments, and help us determine the best time to begin them.”
Huntington’s disease is a rare genetic disorder caused by a single defective gene, dubbed “huntingtin,” on human chromosome 4. The gene is passed on from parents to children — if one parent has the mutation, each child has a 50% chance of inheriting it. Huntington’s disease has no cure and can lead to emotional disturbances, loss of intellectual abilities and uncontrolled movements. Thanks to genetic testing, people can know if they have the disease long before symptoms arise, which typically happens in their 40s or 50s.
For the study, Duan and her team collaborated with colleagues from Kennedy Krieger Institute in Baltimore, Maryland, who developed a novel method to more precisely measure the blood volume in the brain by using advanced functional MRI scans. With the scans, they can map the trajectory of blood flow in small blood vessels called arterioles in the brains of mice engineered to carry the human huntingtin gene mutation that mirror the early stages of Huntington’s disease in humans.
Duan notes that there are many known metabolic changes in the brains of people with Huntington’s disease, and those changes initiate a brain blood volume response in the disease’s early stages. Blood volume is a key marker for oxygen supply to brain cells, which in turn supplies energy for the neurons to function. But with Huntington’s disease, the brain’s arteriolar blood volume is dramatically diminished, which makes the neurons deteriorate because of lack of oxygen as the disease progresses.