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Laughter May Be Best Medicine — For Brain Surgery

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Neuroscientists at Emory University School of Medicine have discovered a focal pathway in the brain that when electrically stimulated causes immediate laughter, followed by a sense of calm and happiness, even during awake brain surgery. The effects of stimulation were observed in an epilepsy patient undergoing diagnostic monitoring for seizure diagnosis. These effects were then harnessed to help her complete a separate awake brain surgery two days later.

The behavioral effects of direct electrical stimulation of the cingulum bundle, a white matter tract in the brain, were confirmed in two other epilepsy patients undergoing diagnostic monitoring. The findings are scheduled for publication in the Journal of Clinical Investigation. Videos of the effects of cingulum bundle stimulation are available, with the patient’s identity obscured.

Emory neurosurgeons see the technique as a “potentially transformative” way to calm some patients during awake brain surgery, even for people who are not especially anxious. For optimal protection of critical brain functions during surgery, patients may need to be awake and not sedated, so that doctors can talk with them, assess their language skills, and detect impairments that may arise from resection.

“Even well-prepared patients may panic during awake surgery, which can be dangerous,” says lead author Kelly Bijanki, PhD, assistant professor of neurosurgery.

“This particular patient was especially prone to it because of moderate baseline anxiety. And upon waking from global anesthesia, she did indeed begin to panic. When we turned on her cingulum stimulation, she immediately reported feeling happy and relaxed, told jokes about her family, and was able to tolerate the awake procedure successfully.”

Outside of use during awake surgery, understanding how cingulum bundle stimulation works could also inform efforts to better treat depression, anxiety disorders, or chronic pain via deep brain stimulation.

Previous investigators have reported that direct electrical stimulation of other parts of the brain can trigger laughter, but the demonstration that anti-anxiety effects observed with cingulum bundle stimulation can provide meaningful clinical benefits make this study distinct, says senior author Jon T, Willie, MD, PhD, who performed the surgeries reported in the paper. He is assistant professor of neurosurgery and neurology at Emory University School of Medicine.

Additional Emory authors include Joseph Manns, PhD, Cory Inman, PhD, graduate student Sahar Harati , Nigel Pedersen, MD, Daniel Drane, PhD, and Rebecca Fasano, MD. Authors who are now at Mount Sinai in New York City are Ki Sueng Choi, PhD, Allison Waters, PhD and Helen Mayberg, MD, all previously at Emory.

Lying under the cortex and curving around the midbrain, the cingulum bundle has a shape resembling a girdle or belt — hence its Latin name. The area that was a key to laughter and relaxation lies at the top and front of the bundle. The bundle is a logical target because of its many connections among brain regions coordinating complex emotional responses, Willie says.

The location of cingulum bundle stimulation is distinct from other brain locations that process reward, such as ventral striatum, which has been targeted for the treatment of depression and addiction. Because the cingulum bundle is a crossroads for white matter connecting several lobes, Willie and his team may be affecting widespread networks throughout the brain.

Willie says the locations of initial electrode placement were chosen in order to record brain activity and locate the onset of the first patient’s seizures. The electrode initially used to stimulate the cingulum bundle was inserted into the brain in a way that was different than standard, he says. The unique trajectory was necessary because of the first patient’s previous surgeries; the approach was from the rear (see illustration), leading to a broader extent of cingulum bundle being sampled and therefore accessible for electrical stimulation.

The JCI paper says that cingulum bundle stimulation “immediately elicited mirthful behavior, including smiling and laughing, and reports of positive emotional experience.”

“The patient described the experience as pleasant and relaxing and completely unlike any component of her typical seizure or aura,” the authors write.

“She reported an involuntary urge to laugh that began at the onset of stimulation and evolved into a pleasant, relaxed feeling over the course of a few seconds of stimulation.”

As a test of her mood and thought processes, the researchers tested how the first patient viewed faces and whether she interpreted them as happy, sad or neutral. Cingulum bundle stimulation shifted her view of faces so that they were interpreted as happier. This effect, called “affective bias” is known to correspond with the reduction of depressive symptoms, and suggests a potential use of cingulum stimulation in treating depression.

The two other patients that underwent cingulum stimulation and behavioral testing did not undergo awake surgery for epilepsy treatment. Upon stimulation, they both also smiled and reported mood elevation and pain relief, and at higher levels of current, experienced laughter. During stimulation, one of the later patients took tests of attention, memory and language and performed normally, except for delayed verbal recall on a list-learning task.

The researchers envision cingulum bundle stimulation as potentially applicable to surgery for brain tumors, as well as epilepsy.

“We could be surer of safe boundaries for removal of pathological tissue and preservation of tissue encoding critical human functions such as language, emotional, or sensory functions, which can’t be evaluated with the patient sedated,” Bijanki says.

“In addition, although substantial further study is necessary in this area, the cingulum bundle could become a new target for chronic deep brain stimulation therapies for anxiety, mood, and pain disorders.”

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Children Carry Evidence Of Toxins From Home Flooring And Furniture

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Children living in homes with all vinyl flooring or flame-retardant chemicals in the sofa have significantly higher concentrations of potentially harmful semi-volatile organic compounds (SVOCs) in their blood or urine than children from homes where these materials are not present, according to a new Duke University-led study.

The researchers presented their findings Sunday, Feb. 17 at the annual meeting of the American Association for the Advancement of Science in Washington, D.C.

They found that children living in homes where the sofa in the main living area contained flame-retardant polybrominated diphenyl ethers (PBDEs) in its foam had a six-fold higher concentration of PBDEs in their blood serum.

Exposure to PBDEs has been linked in laboratory tests to neurodevelopmental delays, obesity, endocrine and thyroid disruption, cancer and other diseases.

Children from homes that had vinyl flooring in all areas were found to have concentrations of benzyl butyl phthalate metabolite in their urine that were 15 times higher than those in children living with no vinyl flooring.

Benzyl butyl phthalate has been linked to respiratory disorders, skin irritations, multiple myeolma and reproductive disorders.

“SVOCs are widely used in electronics, furniture and building materials and can be detected in nearly all indoor environments,” said Heather Stapleton, an environmental chemist at Duke’s Nicholas School of the Environment, who led the research.

“Human exposure to them is widespread, particularly for young children who spend most of their time indoors and have greater exposure to chemicals found in household dust.”

“Nonetheless, there has been little research on the relative contribution of specific products and materials to children’s overall exposure to SVOCs,” she noted.

To address that gap, in 2014 Stapleton and colleagues from Duke, the Centers for Disease Control & Prevention, and Boston University began a three-year study of in-home exposures to SVOCs among 203 children from 190 families.

“Our primary goal was to investigate links between specific products and children’s exposures, and to determine how the exposure happened — was it through breathing, skin contact or inadvertent dust inhalation,” Stapleton said.

To that end, the team analyzed samples of indoor air, indoor dust and foam collected from furniture in each of the children’s homes, along with a handwipe sample, urine and blood from each child.

“We quantified 44 biomarkers of exposure to phthalates, organophosphate esters, brominated flame retardants, parabens, phenols, antibacterial agents and perfluoroalkyl and polyfluoroalkyl substances (PFAS),” Stapleton said.

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Your Home Is A Hidden Source Of Air Pollution

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Cooking, cleaning and other routine household activities generate significant levels of volatile and particulate chemicals inside the average home, leading to indoor air quality levels on par with a polluted major city, University of Colorado Boulder researchers have found.

What’s more, airborne chemicals that originate inside a house don’t stay there: Volatile organic compounds (VOCs) from products such as shampoo, perfume and cleaning solutions eventually escape outside and contribute to ozone and fine particle formation, making up an even greater source of global atmospheric air pollution than cars and trucks do.

The previously underexplored relationship between households and air quality drew focus today at the 2019 AAAS Annual Meeting in Washington, D.C., where researchers from CU Boulder’s Cooperative Institute for Research in Environmental Sciences (CIRES) and the university’s Department of Mechanical Engineering presented their recent findings during a panel discussion.

“Homes have never been considered an important source of outdoor air pollution and the moment is right to start exploring that,” said Marina Vance, an assistant professor of mechanical engineering at CU Boulder.

“We wanted to know: How do basic activities like cooking and cleaning change the chemistry of a house?”

In 2018, Vance co-led the collaborative HOMEChem field campaign, which used advanced sensors and cameras to monitor the indoor air quality of a 1,200-square-foot manufactured home on the University of Texas Austin campus. Over the course of a month, Vance and her colleagues conducted a variety of daily household activities, including cooking a full Thanksgiving dinner in the middle of the Texas summer.

While the HOMEChem experiment’s results are still pending, Vance said that it’s apparent that homes need to be well ventilated while cooking and cleaning, because even basic tasks like boiling water over a stovetop flame can contribute to high levels of gaseous air pollutants and suspended particulates, with negative health impacts.

To her team’s surprise, the measured indoor concentrations were high enough that that their sensitive instruments needed to be recalibrated almost immediately.

“Even the simple act of making toast raised particle levels far higher than expected,” Vance said.

“We had to go adjust many of the instruments.”

Indoor and outdoor experts are collaborating to paint a more complete picture of air quality, said Joost de Gouw, a CIRES Visiting Professor. Last year, de Gouw and his colleagues published results in the journal Science showing that regulations on automobiles had pushed transportation-derived emissions down in recent decades while the relative importance of household chemical pollutants had only gone up.

“Many traditional sources like fossil fuel-burning vehicles have become much cleaner than they used to be,” said de Gouw.

“Ozone and fine particulates are monitored by the EPA, but data for airborne toxins like formaldehyde and benzene and compounds like alcohols and ketones that originate from the home are very sparse.”

While de Gouw says that it is too early on in the research to make recommendations on policy or consumer behavior, he said that it’s encouraging that the scientific community is now thinking about the “esosphere,” derived from the Greek word ‘eso,’ which translates to ‘inner.’

“There was originally skepticism about whether or not these products actually contributed to air pollution in a meaningful way, but no longer,” de Gouw said.

“Moving forward, we need to re-focus research efforts on these sources and give them the same attention we have given to fossil fuels. The picture that we have in our heads about the atmosphere should now include a house.”

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Diet Drinks May Be Associated With Strokes Among Post-Menopausal Women

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Among post-menopausal women, drinking multiple diet drinks daily was associated with an increase in the risk of having a stroke caused by a blocked artery, especially small arteries, according to research published in Stroke, a journal of the American Heart Association.

This is one of the first studies to look at the association between drinking artificially sweetened beverages and the risk of specific types of stroke in a large, racially diverse group of post-menopausal women. While this study identifies an association between diet drinks and stroke, it does not prove cause and effect because it was an observational study based on self-reported information about diet drink consumption.

Compared with women who consumed diet drinks less than once a week or not at all, women who consumed two or more artificially sweetened beverages per day were:

  • 23 percent more likely to have a stroke;
  • 31 percent more likely to have a clot-caused (ischemic) stroke;
  • 29 percent more likely to develop heart disease (fatal or non-fatal heart attack); and
  • 16 percent more likely to die from any cause.

Researchers found risks were higher for certain women. Heavy intake of diet drinks, defined as two or more times daily, more than doubled stroke risk in:

  • women without previous heart disease or diabetes, who were 2.44 times as likely to have a common type of stroke caused by blockage of one of the very small arteries within the brain;
  • obese women without previous heart disease or diabetes, who were 2.03 times as likely to have a clot-caused stroke; and
  • African-American women without previous heart disease or diabetes, who were 3.93 times as likely to have a clot-caused stroke.

“Many well-meaning people, especially those who are overweight or obese, drink low-calorie sweetened drinks to cut calories in their diet. Our research and other observational studies have shown that artificially sweetened beverages may not be harmless and high consumption is associated with a higher risk of stroke and heart disease,” said Yasmin Mossavar-Rahmani, Ph.D., lead author of the study and associate professor of clinical epidemiology and population health at the Albert Einstein College of Medicine in the Bronx, New York.

Researchers analyzed data on 81,714 postmenopausal women (age 50-79 years at the start) participating in the Women’s Health Initiative study that tracked health outcomes for an average of 11.9 years after they enrolled between 1993 and 1998. At their three-year evaluation, the women reported how often in the previous three months they had consumed diet drinks such as low calorie, artificially sweetened colas, sodas and fruit drinks. The data collected did not include information about the specific artificial sweetener the drinks contained.

The results were obtained after adjusting for various stroke risk factors such as age, high blood pressure, and smoking. These results in postmenopausal women may not be generalizable to men or younger women. The study is also limited by having only the women’s self-report of diet drink intake.

“We don’t know specifically what types of artificially sweetened beverages they were consuming, so we don’t know which artificial sweeteners may be harmful and which may be harmless,” Mossavar-Rahmani said.

The American Heart Association recently published a science advisory that found there was inadequate scientific research to conclude that low-calorie sweetened beverages do – or do not – alter risk factors for heart disease and stroke in young children, teens or adults. The Association recognizes diet drinks may help replace high calorie, sugary beverages, but recommends water (plain, carbonated and unsweetened flavored) as the best choice for a no calorie drink.

“Unfortunately, current research simply does not provide enough evidence to distinguish between the effects of different low-calorie sweeteners on heart and brain health. This study adds to the evidence that limiting use of diet beverages is the most prudent thing to do for your health,” said Rachel K. Johnson, Ph.D., R.D., professor of nutrition emeritus, University of Vermont and the chair of the writing group for the American Heart Association’s science advisory, Low-Calorie Sweetened Beverages and Cardiometabolic Health.

“The American Heart Association suggests water as the best choice for a no-calorie beverage. However, for some adults, diet drinks with low calorie sweeteners may be helpful as they transition to adopting water as their primary drink. Since long-term clinical trial data are not available on the effects of low-calorie sweetened drinks and cardiovascular health, given their lack of nutritional value, it may be prudent to limit their prolonged use” said Johnson.

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