What happens in the human brain when we learn from positive and negative experiences? To help answer that question and better understand decision-making and human behavior, scientists are studying dopamine.
Dopamine is a neurotransmitter produced in the brain that serves as a chemical messenger, facilitating communication between nerve cells in the brain and the body. It is involved in functions such as movement, cognition and learning. While dopamine is most known for its association with positive emotions, scientists are also exploring its role in negative experiences.
Now, a new study from researchers at Wake Forest University School of Medicine shows that dopamine release in the human brain plays a crucial role in encoding both reward and punishment prediction errors. This means that dopamine is involved in the process of learning from both positive and negative experiences, allowing the brain to adjust and adapt its behavior based on the outcomes of these experiences.
The study was published today in Science Advances.
"Previously, research has shown that dopamine plays an important role in how animals learn from 'rewarding' (and possibly 'punishing') experiences. But, little work has been done to directly assess what dopamine does on fast timescales in the human brain," said Kenneth T. Kishida, Ph.D., associate professor of physiology and pharmacology and neurosurgery at Wake Forest University School of Medicine. "This is the first study in humans to examine how dopamine encodes rewards and punishments and whether dopamine reflects an 'optimal' teaching signal that is used in today's most advanced artificial intelligence research."
For the study, researchers on Kishida's team utilized fast-scan cyclic voltammetry, an electrochemical technique, paired with machine learning, to detect and measure dopamine levels in real-time (i.e., 10 measurements per second). However, this method is challenging and can only be performed during invasive procedures such as deep-brain stimulation (DBS) brain surgery. DBS is commonly employed to treat conditions such as Parkinson's disease, essential tremor, obsessive-compulsive disorder and epilepsy.
Kishida's team collaborated with Atrium Health Wake Forest Baptist neurosurgeons Stephen B. Tatter, M.D., and Adrian W. Laxton, M.D., who are also both faculty members in the Department of Neurosurgery at Wake Forest University School of Medicine, to insert a carbon fiber microelectrode deep into the brain of three participants at Atrium Health Wake Forest Baptist Medical Center who were scheduled to receive DBS to treat essential tremor.
While the participants were awake in the operating room, they played a simple computer game. As they played the game, dopamine measurements were taken in the striatum, a part of the brain that is important for cognition, decision-making, and coordinated movement
A new study from Mass Eye and Ear investigators shows that individuals who report tinnitus, which present as a ringing in the ears in more than one out of ten adults worldwide, are experiencing auditory nerve loss that is not picked up by conventional hearing tests. This work is part of a P50 grant awarded by the National Institutes of Health (NIH) to Mass Eye and Ear researchers within the Eaton-Peabody Laboratories (EPL) for their work on cochlear synaptopathy, which is commonly referred to as "hidden hearing loss." The results from this study provide a better understanding on the origins of tinnitus and are published November 30th inScientific Reports.
"Beyond the nuisance of having persistent ringing or other sounds in the ears, tinnitus symptoms are debilitating in many patients, causing sleep deprivation, social isolation, anxiety and depression, adversely affecting work performance, and reducing significantly their quality of life," said senior author Stéphane F. Maison, PhD, CCC-A, a principal investigator at Mass Eye and Ear, a member of Mass General Brigham, and clinical director of the Mass Eye and Ear Tinnitus Clinic.
"We won't be able to cure tinnitus until we fully understand the mechanisms underlying its genesis. This work is a first step toward our ultimate goal of silencing tinnitus."
Many individuals with hearing loss report a buzzing, humming, ringing or even roaring sound in their ears.
It's been a longstanding idea that these symptoms, known as tinnitus, arise as a result of a maladaptive plasticity of the brain.
In other words, the brain tries to compensate for the loss of hearing by increasing its activity, resulting in the perception of a phantom sound, tinnitus.
Until recently though, this idea was disputed as some tinnitus sufferers have normal hearing tests.
However, the discovery of cochlear synaptopathy back in 2009 by Mass Eye and Ear investigators brought back to life this hypothesis as it was evidenced that patients with a normal hearing test can have a significant loss to the auditory nerve.
In view of this paradigm shift in the way researchers and clinicians think about hearing loss, Maison and his team sought to determine if such hidden damage could be associated with the tinnitus symptoms experienced by a cohort of normal hearing participants.
A study supported by the National Institutes of Health suggests that the response of immune system cells inside the protective covering surrounding the brain may contribute to the cognitive decline that can occur in a person with chronic high blood pressure. This finding, published inNature Neuroscience, may shed light on new ways to counteract the effects of high blood pressure on cognition. The study was funded by the National Institute of Neurological Disorders and Stroke (NINDS), a part of NIH.
"The role of immune signaling in cognitive decline is critically important to understand," said Roderick Corriveau, Ph.D., program director, NINDS.
"These findings offer insight into how signaling from the immune system could contribute to symptoms of cognitive decline that ultimately result in dementia diagnoses."
Hypertension affects more than 1 billion people worldwide and can lead to a decline in cognitive function including when a stroke occurs, but also even when a person with high blood pressure does not have a stroke.
However, efforts to control cognitive loss in people who do not experience a stroke with treatments that lower blood pressure have shown mixed results.
The findings of this mouse study suggest that immune cells around and within the brain become abnormally activated under conditions that mimic a common form of hypertension, and this activation leads to impaired brain function.
Using a mouse model of high blood pressure, the researchers led by Costantino Iadecola, M.D., director and chair of the Feil Family Brain and Mind Research Institute, New York City, found abnormally increased levels of interleukin-17 (IL-17), a chemical normally released in the body to activate the immune system, in the cerebral spinal fluid and the brain.
Previously, Dr. Iadecola's team showed that a high salt diet increased IL-17 in the gut, which was followed by cognitive impairment.
These new findings add to that story by showing that IL-17 is acting within the brain itself.
Ketamine -- an anesthetic also known for its illicit use as a recreational drug -- has undergone a thorough reputational rehabilitation in recent years as the medical establishment has begun to recognize its wide-ranging therapeutic effects. The drug is increasingly used for a range of medical purposes, including as a painkiller alternative to opioids, and as a therapy for treatment-resistant depression.
In a new study published in the journal Cell Reports, Columbia biologists and biomedical engineers mapped ketamine's effects on the brains of mice, and found that repeated use over extended periods of time leads to widespread structural changes in the brain's dopamine system.
The findings bolster the case for developing ketamine therapies that target specific areas of the brain, rather than administering doses that wash the entire brain in ketamine.
"Instead of bathing the entire brain in ketamine, as most therapies now do, our whole-brain mapping data indicates that a safer approach would be to target specific parts of the brain with it, so as to minimize unintended effects on other dopamine regions of the brain," Raju Tomer, the senior author of the paper said.
The study found that repeated ketamine exposure leads to a decrease in dopamine neurons in regions of the midbrain that are linked to regulating mood, as well as an increase in dopamine neurons in the hypothalamus, which regulates the body's basic functions like metabolism and homeostasis.
The former finding, that ketamine decreases dopamine in the midbrain, may indicate why long-term abuse of ketamine could cause users to exhibit similar symptoms to people with schizophrenia, a mood disorder.
The latter finding, that ketamine increases dopamine in the parts of the brain that regulate metabolism, on the other hand, may help explain why it shows promise in treating eating disorders.
The researchers' highly-detailed data also enabled them to track how ketamine affects dopamine networks across the brain.
They found that ketamine reduced the density of dopamine axons, or nerve fibers, in the areas of the brain responsible for our hearing and vision, while increasing dopamine axons in the brain's cognitive centers.
These intriguing findings may help explain the dissociative behavioral effects observed in individuals exposed to ketamine.
"The restructuring of the brain's dopamine system that we see after repeated ketamine use may be linked to cognitive behavioral changes over time," Malika Datta, a co-author of the paper said.
Most studies of ketamine's effects on the brain to-date have looked at the effects of acute exposure -- how one dose affects the brain in the immediate term.
For this study, researchers examined repeated daily exposure over the course of up to ten days.
Statistically significant alterations to the brain's dopamine makeup were only measurably detectable after ten days of daily ketamine use.
Contrary to current understanding, the brains of human newborns aren't significantly less developed compared to other primate species, but appear so because so much brain development happens after birth, finds a new study led by UCL researchers.
The study, published in Nature Ecology & Evolution, found that humans are born with brains at a development level that's typical for similar primate species, but the human brains grow so much larger and more complex than other species after birth, it gives the false impression that human newborns are underdeveloped, or "altricial."
Lead author Dr Aida Gomez-Robles (UCL Anthropology) said: "This new work changes the overall understanding around the evolution of human brain development. Humans seem so much more helpless when they're young compared to other primates not because their brains are comparatively underdeveloped but because they still have much further to go."
One way that scientists compare the brain development of different species is by measuring the size of their brains as newborns to their brain size as adults.
Humans are born with a relatively smaller percentage of their adult brain size, compared to other primates, making it seem they're born less developed.
However, this new research shows that this measure is misleading as other measurements of human brain development show humans are largely in line with other species of primates such as chimpanzees, bonobos, gorillas and orangutans.
The research challenges a prevailing understanding of evolutionary human brain development.
Up to now, because of their helplessness and poor muscle control, it's long been believed that humans are born with comparatively less developed brains than other primates.
This was thought to be the result of an evolutionary compromise so babies' heads could fit through their mother's birth canal, which would require them to further develop outside of the womb.
Based on this understanding, scientists suggested that because humans emerged comparatively underdeveloped, their brains are more malleable in the earliest period of life and more easily affected by environmental stimuli as they grow.
Vitamin D is an essential nutrient, and researchers are interested in how it may help in several health areas.
One area of interest is how much vitamin D supplementation is required to achieve potential cardiac benefits.
An initial analysis in a clinical trial suggests that the current recommended dietary allowance of vitamin D in the United States is too low to achieve optimal vitamin D levels for people with certain cardiac problems.
Future research in this area will seek to determine if achieving optimal vitamin D levels can decrease the risk for adverse cardiovascular events.
Research is ongoing about the health benefits of vitamin D. One area of interest is how vitamin D may help reduce the risk of heart problems.
Researchers at Intermountain Health are conducting an ongoing clinical trial looking into this topic, and their first analysis is already complete.
Reports shared at the American Heart Association’s Scientific Sessions 2023Trusted Source suggest that current recommended dietary allowances are inadequate for achieving optimal serum vitamin D levels.
In this trial’s next phase, researchers will examine if optimal vitamin D levels are associated with a decreased risk for adverse cardiovascular events such as heart attack and stroke.
Vitamin D is an essential nutrient and contributes to proper bone function. Research is ongoing about how vitamin D may promote health in other areas, including cardiovascular health.
However, the National Institutes of Health (NIH)Trusted Source note that current evidence does not seem to support the claim that taking vitamin D supplements helps reduce risks for cardiovascular disease.
Dr. Mary Greene, from Manhattan Cardiology in New York, and contributor to LabFinder, not involved in the current research, explained to Medical News Today that “[m]any studies have failed to demonstrate if supplementation with Vitamin D can prevent major adverse cardiovascular events.”
She added:
“There are several proposed mechanisms by which vitamin D may contribute to cardiovascular health. Having healthy vitamin D levels may promote glucose metabolism and insulin sensitivity, may promote endothelial function in the blood vessels, may regulate blood pressure and blood volume homeostasis and may inhibit inflammation. Due to these effects, vitamin D helps to regulate the underlying dysfunction that causes heart disease.”
Dr. Cheng-Han Chen, a board-certified interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, CA, also not involved in the current research, further noted that: “Vitamin D deficiency has been considered a possible risk factor in cardiovascular disease. However, studies which examined the effect of vitamin D supplementation have not found a clear benefit of Vitamin D in preventing cardiovascular events.”
“Past observational studies have noted an association between low Vitamin D levels and increased risk of a cardiovascular event such as heart attack or stroke. However, the reasons behind this association are not clear. It is hypothesized that Vitamin D receptors in cells throughout the vascular system are involved in blood vessel inflammation, which could in turn promote heart disease,” he detailed.
Currently, the recommended dietary allowance for vitamin D is 600 international units (IU)Trusted Source, or approximately 15 micrograms (mcg), for adults under 70 years of age, and 800 IU, or around 20 mcg, for adults over 70.
However, according to the researchers who conducted the current clinical trial, this might not be enough for people to reach appropriate serum levels of vitamin D.
They suggest that participants in other studies were not given high enough doses of vitamin D to achieve a therapeutic response.
The authors of the current clinical trial wanted to understand more about optimal dosing to help people reach appropriate vitamin D levels and whether or not this aids in preventing adverse cardiovascular events.
For this clinical trial — called TARGET-D — they have recruited 632 participants. All of these participants had experienced acute coronary syndromeTrusted Source. This refers to a group of events with decreased blood flow to the heart. For example, someone who experienced a heart attack would have acute coronary syndrome.
Researchers then divided participants into the vitamin D intervention group and the group receiving standard care. Instead of just giving a standard dose of vitamin D, researchers went off of participants’ specific vitamin D levels and provided supplementation as needed.
In the first part of their analysis, they found that most participants required vitamin D supplementation to reach a serum vitamin D level of more than 40 nanograms per milliliter (ng/mL).
When determining what doses to give participants to reach this level, they found that 51% needed between 5,000-8,000 IU, much higher than the recommended dietary allowance. Additionally, 14.6% of participants required 10,000 IU or more to reach optimal vitamin D levels.
It also took time for participants to reach the target vitamin D level. Less than 65% of participants reached the level at three months, and 25% required six months of intervention to reach the level.
The results indicate that higher vitamin D doses are required to reach therapeutic levels in this group.
Study author Dr. Heidi May, a cardiovascular epidemiologist with Intermountain Health, explained some of the key components of the clinical trial to MNT:
“TARGET-D is a randomized clinical trial that is evaluating whether obtaining a blood vitamin D level>40 ng/mL reduces adverse cardiovascular outcomes. We have found this association in prior observational studies, but a randomized clinical study is needed to determine if there is a causation relation. We were not surprised that so many patients had levels [lower than or equal to] 40 ng/mL, but how much vitamin D supplementation was needed to achieve this level.”
A new study of people with chronic kidney disease indicates there is accelerated biological aging from the disease.
The researchers reported that the accelerated aging was slowed by kidney transplantation but not dialysis.
Through this study, researchers say they were able to develop a more accurate “epigenetic clock” to help determine biological age in people with as well as without kidney disease.
In the study of aging, there are generally two categories: The age you have by the calendar and the age you are biologically.
The former is straightforward. Understanding the latter is very much an emerging science.
Key to this new science of aging is the concept of the “epigenetic clock,” which involves examining DNA for signs of aging and comparing that to a person’s chronological age.
A research team from the Karolinska Institutet in Sweden and the University of Glasgow in Scotland believe they’ve developed a fitter, more accurate epigenetic clock from a study of people with chronic kidney disease (CKD).
The research team used existing measures of biological age to compare the effects of dialysis treatment and kidney transplantation on patients’ epigenetic clocks compared to healthy tissue.
People with chronic kidney disease were chosen partly because the condition is known to produce hallmarks of accelerated aging, making it a good target for this sort of study
Their researchers’ findings were published in the Journal of Internal MedicineTrusted Source.
“Biological age provides a more comprehensive understanding of a person’s aging process and reflects how well their body is functioning compared to what is expected at their chronological age,” said Dr. Gil Blander, PhD, the founder and chief scientific officer at the biomedical company InsideTracker, who was not involved in the study.
The researchers examined a cohort of 400 people with chronic kidney disease and 100 “control” participants.
They also monitored 47 people after they began kidney dialysis or one year after kidney transplantation. They then compared that to the healthy tissue of 48 similarly chronologically-aged people.
The scientist reported that biological clocks kept ticking faster among people on dialysis compared to a person who received a kidney transplantation or people without kidney disease.
“These results are not surprising since dialysis only provides a temporary solution to the disease outcome, whereas successful transplantation is a real reversal of the disease,” Dr. Blander told Medical News Today.
However, Dr. Nathan Goodyear, an integrative medicine practitioner and the medical director of Brio-Medical, disagreed. He explained to MNT:
“The surgical-associated stress, immune dysfunction associated with surgery, and the chronic immune suppression from the chronic immunosuppression required post transplantation would likely accelerate epigenetic modification, aging, and its associated biological aging. Yet, the restoration of the ability of the body to restore optimal detoxification oxidant/antioxidant balance [via a new kidney] to maintain optimal mitochondrial energy production slowed epigenetic modification and slow epigenetic aging — and biological aging as a result.”
The researchers reported that initial epigenetic clocks showed that chronic kidney disease accelerated biological aging, but the clocks didn’t necessarily sync.
In addition, none of the clocks were completely accurate compared to actual clinical results and were all inaccurate when tested against healthy tissue.
That led the team to develop a new epigenetic clock based on these results using “methylation tagging” that worked in both diseased and healthy tissue.
This is a refinement of existing techniques, as methylation is a natural byproduct of the aging process where methyl groups accrue in DNA, reducing gene transcription and altering a person’s phenotype — their observable characteristics.
“This is the first clinical test of epigenetic clocks, and the discovery that most are inaccurate when compared with medical evidence has led us to develop a new, more accurate test we have proven is accurate to the high standards of a clinical setting,” said Helen Erlandsson, a PhD student and lead study author from the Karolinska Institutet, in a press release.
“Methylation tagging of DNA is impacted by what we eat and also our gut microbiome. As a result, this new clock has real potential to be able to evaluate lifestyle interventions, including diet, that could benefit the public and help to address issues such as health inequalities.”
However, not everyone agrees on the science of the usefulness of epigenetic clocks as a tool.
“Epigenetic clocks are a fad right now,” said Dr. Charles Brenner, the chair of Diabetes and Cancer Metabolism at City of Hope and the chief scientific advisor at aging science research company ChromaDex who was not involved in the study.
“They are an attempt to quantify biological aging using biomarkers that can be measured in blood,” he told MNT. “There is no consumer use case for epigenetic clocks. If people want to know their biological age, they can compare their fitness to other people their age. It’s function that matters.”
To that end, epigenetics isn’t the be-all and end-all of a person’s biological age.
“It’s important to know that our lifestyle plays a major role in the aging process, accounting for up to 93 percent [of aging],” Dr. Blander said. “Factors such as environment, diet, physical activity, and sleep are just a few examples.”
Dr. Brenner agreed, noting the following to MNT:
“Eating right, staying physically and mentally active, socially engaged, prioritizing sleep, and avoiding drugs and alcohol are the most important steps. We think there is also a use case for nicotinamide riboside in preserving youthful resiliency. This is a form of vitamin B3 that is undergoing extensive clinical testing for diseases and conditions of metabolic stress and aging.”
The recent popularity of the world’s Blue Zones has led to increased interest in how a person can not only live longer but also age healthier.
Previous research highlights some things people can do for healthier aging.
Researchers from the National Institute on Aging have discovered that calorie restriction improves muscle health and stimulates biological pathways important for healthy aging.
With the recent popularity of the world’s so-called Blue Zones, where people tend to live longer than elsewhere on the Globe, there has been a lot of interest and discussion on how a person can not only increase their longevity but also age healthier.
Previous research shows that lifestyle interventions, such as staying activeTrusted Source, following a healthy dietTrusted Source, practicing good sleep hygieneTrusted Source, not smoking, and limiting alcoholTrusted Source intake can help people lead healthier lives for longer.
Now, researchers from the National Institutes of Health’s National Institute on Aging have discovered that calorie restriction can improve muscle health and stimulates biological pathways important for healthy aging.
Their study recently appeared in the journal Aging CellTrusted Source.
Calorie restrictionTrusted Source is the process of lowering the average amount of calories a person would normally consume in a day without depriving themselves of the essential vitamins and minerals they need to stay healthy.
An average person needs between 1,600 to 3,000 calories a day, depending on their biological sex, height, age, and activity level.
A calorie-restricted diet reduces food intake by between 20% to 40% while still meeting the recommended daily intake of essential nutrients.
When following a calorie-restricted diet, it is important to talk to a doctor or nutritionist first as cutting too many calories can lead to health issues.
Intermittent fasting can also be used as an alternative to calorie restriction as research shows it offers many of the same benefitsTrusted Source.
For many years, researchers have studied how calorie restriction affects a person’s overall health.
Previous studies show eating fewer calories each day can support weight lossTrusted Source and improve cardiovascular healthTrusted Source and cognitive functionTrusted Source.
The current study is also not the first to link calorie restriction with longevity. Research published in April 2016 found that calorie restriction helps protect the body from aging through inflammation preventionTrusted Source and other mechanisms.
Moreover, a study published in September 2017 reported that calorie restriction may lead to positive changes in the genesTrusted Source associated with aging.
And research published in February 2022 found that following a calorie-restricted diet may help increase a person’s “health span.”
For this study, scientists examined how calorie restriction helped improve muscle health and conserve muscle function, as a declineTrusted Source in muscle mass and function is known to occur with aging.
“Previous studies have found that while people on calorie restriction were losing muscle mass, they did not lose muscle strength, which suggests that something occurred in the muscle that improves their performance, [and] we wanted to know what,” Dr. Luigi FerrucciTrusted Source, scientific director of the National Institute on Aging and corresponding author of this study explained to Medical News Today.
“Also, there is evidence in animal models that [calorie restriction] enhances the production of spliced variants of different proteins,” he added.
Dr. Ferrucci and his team analyzed data from study participants in the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE)Trusted Source study. This study, supported by the National Institute on Aging, looked at whether moderate calorie restriction in humans offered the same health benefits seen in animal studies.
Although CALERIE study participants were asked to achieve a 25% calorie reduction over 2 years, the highest the group reached was a 12% reduction.
The scientists used thigh muscle biopsies from CALERIE participants to examine how calorie restriction affects human genes.
Using messenger RNA (mRNA) molecules isolated from the biopsies, researchers found that consuming fewer calories upregulated the genes associated with energy generation and metabolism, and downregulated inflammatory genes, resulting in less inflammation.
When explaining how calorie restriction may affect a person’s genes and lead to healthier aging, Dr. Ferrucci said there are many integrated mechanisms involved:
“The most directly understandable is [an] improvement of mitochondrial health and reduction of inflammation. However, very interesting is also the effect on the clock gene that regulates the rhythm of many metabolisms in our body. Overall, these and other mechanisms improve muscle health and function,"
After reviewing this study, Monique Richard, a registered dietitian nutritionist, owner of Nutrition-In-Sight, and national media spokesperson for the Academy of Nutrition Dietetics, not involved in this research, told MNT that the results of this study are not surprising, judging by data gathered by previous research.
“As we age, cellular processes [and] cell regeneration and turnover slow down,” she explained. “If we work to preserve and support these systems, we will be able to preserve function, support longevity, and quality of life.”
“An analogy would be thinking of our body as a vehicle,” Richard continued. “In order to get the most miles and performance out of a vehicle, it is important to provide quality energy — high-grade gas or electricity for the vehicle, high-quality vitamins, minerals and nutrients for our body — regular maintenance and check-ups for the functional pieces — brakes, tires, [and] engine like our brain, heart, and body — and tender, love, and care.”
“Decreasing excess, nonessential calories, but making sure individual needs are met, will preserve cellular function [and] muscle tissue and extend the ability for cells to function and turnover,” she noted.
MNT also spoke with Dr. David Cutler, a family medicine physician at Providence Saint John’s Health Center in Santa Monica, CA, about this study. Dr. Cutler was not involved in this research.
He commented he was happy this study was done as it helps get the message out to people that it is, in some cases, better to eat less.
“The public health aspects are the most important thing — just getting the message out to people about eating less and the dangers posed by being overweight, by being obese, by having diabetes, and all the other ramifications of overeating,” said Dr. Cutler.
For those looking to cut calories, Dr. Cutler said there are certain food groups to start with.
“I’d start number one with processed meatsTrusted Source,” he detailed. “Any meat that has been salted or cured or processed in any way — the salamis, the bolognas, the hotdogs. These should all be off our list. I think red meat in general should be severely limited. And carbohydrates should be geared towards a much lower glycemic index — less sweet and processed carbohydrates.”
