How immunity contributes to aging and neurodegeneration
August 2, 2023
Science Daily/Ecole Polytechnique Fédérale de Lausanne
Researchers have found that a specific immune signaling pathway drives ageing-related inflammation and neurodegeneration. The work can help us understand the mechanisms behind ageing-associated impairment and disease.
As we age, our bodies undergo various changes that can impact our overall health and make us more susceptible to diseases. One common factor in the ageing process is low-grade inflammation, which contributes to age-related decline and impairment. However, the precise pathways responsible for this inflammation and their impact on natural ageing have remained elusive until now.
A new study led by Andrea Ablasser at EPFL now shows that a molecular signaling pathway called cGAS/STING, plays a critical role in driving chronic inflammation and functional decline during aging. By blocking the STING protein, the researchers were able to suppress inflammatory responses in senescent cells and tissues, leading to improvements in tissue function.
cGAS/STING is a molecular signaling pathway that detects the presence of DNA in cells. It involves two proteins, cyclic GMP-AMP synthase (cGAS) and Stimulator of Interferon Genes (STING). When activated, cGAS/STING triggers an immune response to defend against viral and bacterial infections.
Previous work by Ablasser and her colleagues has linked cGAS/STING to a number of biological processes, including cellular senescence, a hallmark of aging. Based on this, the researchers investigated whether it might underlie maladapted immune responses during ageing.
The research found that activating the STING protein triggers specific patterns of gene activity in microglia, the brain's first-line-of-defense immune cells. These gene-activation patterns matched those arising in microglia in distinct neurodegenerative conditions, such as Alzheimer`s disease and ageing.
"In search for a mechanism that would engage the cGAS-STING pathway in ageing, we considered aberrant mitochondrial DNA species," says Ablasser. "Mitochondria, the organelles that are responsible for energy production are well-known for disturbed functioning in ageing and disease. Indeed, in microglia from old, but not young mice, DNA from mitochondria accumulated in the cell cytoplasm, suggesting a possible mechanism by which the cGAS-STING pathway contributes to inflammation in the ageing brain."
The researchers studied the effects of blocking the STING protein in aged mice. As expected by its central role in driving inflammation, inhibiting STING alleviated markers of inflammation both in the periphery and in the brain. More importantly, animals receiving STING inhibitors displayed significant enhancements in spatial and associative memory. STING blockade also affected physical function with improved muscle strength and endurance.
The study advances our understanding of ageing-related inflammation and also offers potential strategies for slowing cognitive deterioration in age-associated neurodegenerative conditions. The precise elucidation of the neuroimmune crosstalk governing microglial-dependent neurotoxicity also holds promise for the future study of neurodegenerative diseases.
https://www.sciencedaily.com/releases/2023/08/230802132023.htm
Minds & eyes: Study shows dementia more common in older adults with vision issues
Even when wearing their glasses or contacts, those who scored worse on vision tests were also more likely to have concerning scores on cognitive tests
August 1, 2023
Science Daily/Michigan Medicine - University of Michigan
Losing the ability to see clearly, and losing the ability to think or remember clearly, are two of the most dreaded, and preventable, health issues associated with getting older.
Now, a new study lends further weight to the idea that vision problems and dementia are linked.
In a sample of nearly 3,000 older adults who took vision tests and cognitive tests during home visits, the risk of dementia was much higher among those with eyesight problems -- including those who weren't able to see well even when they were wearing their usual eyeglasses or contact lenses.
The research was published recently in JAMA Ophthalmology by a team from the Kellogg Eye Center at Michigan Medicine, the University of Michigan's academic medical center.
Based on data from a nationally representative study of older adults conducted in 2021 through the U-M Institute for Social Research, it adds to a growing pile of studies that have suggested a link between vision and dementia.
All of the older adults in the study were over the age of 71, with an average age of 77. They had their up-close and distance vision, and their ability to see letters that didn't contrast strongly with their background, tested by a visiting team member using a digital tablet. They also took tests of memory and thinking ability, and provided health information including any existing diagnosis of Alzheimer's disease or another form of dementia.
Just over 12% of the whole group had dementia. But that percentage was higher -- nearly 22% -- among those who had impaired vision for seeing up close.
In addition, one-third (33%) of those with moderate or severe distance vision impairment, including those who were blind, had signs of dementia. So did 26% of those who had trouble seeing letters that didn't contrast strongly against a background.
Even among those with a mild distance vision issue, 19% had dementia.
After the researchers adjusted for other differences in health status and personal characteristics, people with moderate to severe distance vision issues were 72% more likely than those with no vision issues to have dementia.
The gaps were smaller, but still large, for other types of vision impairment -- except mild problems with distance vision, where there was no statistical difference.
Those who had more than one kind of vision impairment were also 35% more likely to have dementia than those with normal vision.
The new study builds on previous studies that had similar findings but relied on self-reported vision abilities rather than objective testing, or that were not representative of the U.S. population.
It also builds on previous work about cataract surgery that showed lower rates of dementia over time in adults who had had their distance vision restored by having surgery.
The authors, led by ophthalmologists Olivia Killeen, M.D., M.S. and Joshua Ehrlich, M.D., M.P.H., write, "Prioritizing vision health may be key to optimizing both sight and overall health and well-being. Randomized trials are warranted to determine whether optimizing vision is a viable strategy to slow cognitive decline and reduce dementia risk."
But in the meantime, in an accompanying editorial, Sheila West, Ph.D., of the Wilmer Eye Institute at Johns Hopkins Medicine, wrote that the new study adds to accumulating evidence about the link between vision and cognitive issues.
"Equitable access to vision care services that prevent, reverse, or at least stave off progression of loss of sight is a worthy goal regardless of the potential impact on dementia and may be especially critical for those experiencing cognitive decline," she wrote.
The study is based on data from the National Health and Aging Trends Study, which is based at the U-M Institute for Social Research and the Johns Hopkins University Bloomberg School of Public Health.
Last year, Ehrlich and colleagues published a paper in JAMA Neurology that used another ISR-based survey of older adults -- the Health and Retirement Study -- to estimate the percentage of Americans with dementia whose condition is likely related to their vision loss. They calculated that 1.8 percent of all cases are vision-related, equating to more than 100,000 of the 6 million Americans with dementia. This study suggested that vision impairment should be considered alongside other more commonly recognized modifiable dementia risk factors. That study was funded by the U-M Center to Accelerate Population Research in Alzheimer's (CAPRA) through funding from the National Institute on Aging.
Killeen recently completed the National Clinician Scholars Program at the U-M Institute for Healthcare Policy and Innovation and is now at Duke University. Ehrlich is an assistant professor of Ophthalmology and Visual Sciences at Michigan Medicine and a research assistant professor at ISR, where he is a co-investigator of NHATS, as well as a member of IHPI.
https://www.sciencedaily.com/releases/2023/08/230801172009.htm
New study links brain waves directly to memory
July 31, 2023
Science Daily/University of Arizona
Simply remembering events can trigger brain rhythms, even more so than when people are experiencing the actual event, says a new study. The findings could lay foundations for cognitive impairment therapy and help improve memory.
Neurons produce rhythmic patterns of electrical activity in the brain. One of the unsettled questions in the field of neuroscience is what primarily drives these rhythmic signals, called oscillations. University of Arizona researchers have found that simply remembering events can trigger them, even more so than when people are experiencing the actual event.
The researchers, whose findings are published in the journal Neuron, specifically focused on what are known as theta oscillations, which emerge in the brain's hippocampus region during activities like exploration, navigation and sleep. The hippocampus plays a crucial role in the brain's ability to remember the past.
Prior to this study, it was believed that the external environment played a more important role in driving theta oscillations, said Arne Ekstrom, professor of cognition and neural systems in the UArizona Department of Psychology and senior author of the study. But Ekstrom and his collaborators found that memory generated in the brain is the main driver of theta activity.
"Surprisingly, we found that theta oscillations in humans are more prevalent when someone is just remembering things, compared to experiencing events directly," said lead study author Sarah Seger, a graduate student in the Department of Neuroscience.
The results of the study could have implications for treating patients with brain damage and cognitive impairments, including patients who have experienced seizures, stroke and Parkinson's disease, Ekstrom said. Memory could be used to create stimulations from within the brain and drive theta oscillations, which could potentially lead to improvements in memory over time, he said.
UArizona researchers collaborated on the study with researchers from the University of Texas Southwestern Medical Center in Dallas, including neurosurgeon Dr. Brad Lega and research technician Jennifer Kriegel. The researchers recruited 13 patients who were being monitored at the center in preparation for epilepsy surgery. As part of the monitoring, electrodes were implanted in the patients' brains for detecting occasional seizures. The researchers recorded the theta oscillations in the hippocampus of the brain.
The patients participated in a virtual reality experiment, in which they were given a joystick to navigate to shops in a virtual city on a computer. When they arrived at the correct destination, the virtual reality experiment was paused. The researchers asked the participants to imagine the location at which they started their navigation and instructed them to mentally navigate the route they just passed through. The researchers then compared theta oscillations during initial navigation to participants' subsequent recollection of the route.
During the actual navigation process using the joystick, the oscillations were less frequent and shorter in duration compared to oscillations that occurred when participants were just imagining the route. So, the researchers conclude that memory is a strong driver of theta oscillations in humans.
One way to compensate for impaired cognitive function is by using cognitive training and rehabilitation, Ekstrom said.
"Basically, you take a patient who has memory impairments, and you try to teach them to be better at memory," he said.
In the future, Ekstrom is planning to conduct this research in freely walking patients as opposed to patients in beds and find how freely navigating compares to memory with regard to brain oscillations.
"Being able to directly compare the oscillations that were present during the original experience, and during a later retrieval of that is a huge step forward in the field in terms of designing new experiments and understanding the neural basis of memory," Seger said.
https://www.sciencedaily.com/releases/2023/07/230731170151.htm
People with increased genetic risk of Alzheimer's may lose sense of smell first
July 26, 2023
Science Daily/American Academy of Neurology
People who carry the gene variant associated with the strongest risk for Alzheimer's disease may lose their ability to detect odors earlier than people who do not carry the gene variant, which may be an early sign of future memory and thinking problems, according to a study published in the July 26, 2023, online issue of Neurology®, the medical journal of the American Academy of Neurology. The gene variant associated with this increased risk of Alzheimer's is called APOE e4.
"Testing a person's ability to detect odors may be a useful way to predict future problems with cognition," said study author Matthew S. GoodSmith, MD, of the University of Chicago. "While more research is needed to confirm these findings and determine what level of smell loss would predict future risk, these results could be promising, especially in studies aiming to identify people at risk for dementia early in the disease."
The study involved an at-home survey that included testing the sense of smell of over 865 people -- both their ability to detect an odor at all and their ability to identify what odor they were smelling. Tests were given at five-year intervals. People's thinking and memory skills were also tested twice, five years apart. DNA samples gave researchers information about who carried the gene associated with an increased risk of Alzheimer's.
For the test to see if people could detect odors, scores ranged from zero to six based on how many of the different concentrations of odors they could smell.
People who carried the gene variant were 37% less likely to have good odor detection than people without the gene at a single timepoint. Researchers accounted for other factors that could affect the results, such as age, sex, and educational level. The gene carriers started experiencing reduced smell detection at age 65 to 69. At that age, the gene carriers could detect an average of about 3.2 of the smells, compared to about 3.9 smells for the people who did not carry the gene.
The people carrying the gene variant did not show a difference in their ability to identify what odor they were smelling until they reached age 75 to 79. Once they started to lose their ability to identify odors, the gene carriers' ability declined more quickly than those who did not carry the gene.
Thinking and memory skills were similar among the two groups at the start of the study. But as expected, those carrying the gene variant experienced more rapid declines in their thinking skills over time than those without the gene.
"Identifying the mechanisms underlying these relationships will help us understand the role of smell in neurodegeneration," GoodSmith said.
A limitation of the study is that people with severe dementia were not included.
https://www.sciencedaily.com/releases/2023/07/230726171240.htm
Scientists may have discovered mechanism behind cognitive decline in aging
July 25, 2023
Science Daily/University of Colorado Anschutz Medical Campus
Scientists at the University of Colorado Anschutz Medical Campus have discovered what they believe to be the central mechanism behind cognitive decline associated with normal aging.
"The mechanism involves the mis-regulation of a brain protein known as CaMKII which is crucial for memory and learning," said the study's co-senior author Ulli Bayer, PhD, professor of pharmacology at the University of Colorado School of Medicine. "This study directly suggests specific pharmacological treatment strategies."
The study was published today in the journal Science Signaling.
Researchers using mouse models found that altering the CaMKII brain protein caused similar cognitive effects as those that happen through normal aging.
Bayer said that aging in mice and humans both decrease a process known as S-nitrosylation, the modification of a specific brain proteins including CaMKII.
"The current study now shows a decrease in this modification of CaMKII is sufficient to cause impairments in synaptic plasticity and in memory that are similar in aging," Bayer said.
Normal aging reduces the amount of nitric oxide in the body. That in turn reduces nitrosylation which reduces memory and learning ability, the study said.
Bayer said the new research opens the way toward developing drugs and other therapeutic interventions that could normalize the nitrosylation of the protein. He said that holds out the possibility of treating or staving off normal cognitive decline for an unknown period of time.
He pointed out that this would only work in normal age-related cognitive decline, not the decline seen in Alzheimer's disease and dementia.
"We know this protein can be targeted," Bayer said. "And we think it could be done pharmacologically. That is the next logical step."
https://www.sciencedaily.com/releases/2023/07/230725171914.htm
New study reveals why defense against brain corrosion declines in people with Alzheimer's disease
Findings offer hope for development of new medications
July 24, 2023
Science Daily/Case Western Reserve University
A new study by researchers at Case Western Reserve University revealed that the progression of Alzheimer's disease (AD) can be slowed by suppressing a specific protein in the brain that causes corrosion.
A main pathogenic initiator of AD and related dementias is oxidative stress, which corrodes the brain, called oxidative damage.
David E. Kang, the Howard T. Karsner Professor in Pathology at the Case Western Reserve School of Medicine and the study's lead researcher, said they've identified for the first time a cause for the loss of so-called "oxidative damage defense" in AD.
A protein called Nuclear factor erythroid 2-related factor 2 (Nrf2) is regularly activated in response to oxidative stress to protect the brain from oxidative damage. But in the brain of someone with AD, Nrf2 defense against oxidative stress declines. How that occurs in AD was unknown.
The study, recently published in the peer-reviewed journalPNAS, found that a protein called Slingshot Homolog-1, or SSH1, stops Nrf2 from carrying out its protective biological activity.
Genetically eliminating SSH1 increases Nrf2 activation and slows the development of oxidative damage and buildup of toxic plaques and tangles in the brain -- both risk factors for AD. As a result, the regular connections between brain cells are maintained and degeneration of brain nerve cells is avoided, they found.
The finding is significant because most clinical trials have been conducted with people with advanced dementia. The tests focused mainly on managing and reducing symptoms to enhance daily functioning and quality of life.
"Focusing on clinical trials in the early stages of AD increases the likelihood of success," Kang said. "In the upcoming five years, I also think we'll see modest improvements in treatments for Alzheimer's disease, which will help slow AD's course."
For example, clinical trials for Leqembi -- medication for early AD recently approved by the U.S. Food and Drug Administration -- have shown somewhat promising results to slow progression of the disease.
Case Western Reserve is among those working on SSH1 inhibitor compounds as potential neuroprotective medicines.
"Many promising drug candidates are certainly in the pipeline," Kang said.
https://www.sciencedaily.com/releases/2023/07/230724122745.htm
Bodybuilding supplement may help stave off Alzheimer's
July 22, 2023
Science Daily/Rush University Medical Center
The secret to protecting your memory may be a staple of a bodybuilder's diet. RUSH researchers recently discovered that a muscle-building supplement called beta-hydroxy beta-methylbutyrate, also called HMB, may help protect memory, reduce plaques and ultimately help prevent the progression of Alzheimer's disease.
HMB is not a prescription drug or a steroid, but an over-the-counter supplement that is available in sports and fitness stores. Bodybuilders regularly use HMB to increase exercise-induced gains in muscle size and strength while improving exercise performance. HMB is considered safe even after long-term use, with no known side effects.
"This may be one of the safest and the easiest approaches to halt disease progression and protect memory in Alzheimer's disease patients," said Kalipada Pahan, PhD, the Floyd A. Davis, MD, Professor of Neurology and professor of neurological sciences, biochemistry and pharmacology at RUSH Medical College.
Studies in mice with Alzheimer's disease have shown that HMB successfully reduces plaques and increases factors for neuronal growth to protect learning and memory, according to neurological researchers at RUSH.
"Understanding how the disease works is important to developing effective drugs to protect the brain and stop the progression of Alzheimer's disease," Pahan said.
Previous studies indicate that a family of proteins known as neurotrophic factors are drastically decreased in the brains of people with Alzheimer's disease and have been found to help in survival and function of neurons, which are cells that receive and send messages from the body to the brain and vice versa.
"Our study found that after oral consumption, HMB enters into the brain to increase these beneficial proteins, restore neuronal connections and improve memory and learning in mice with Alzheimer's-like pathology, such as plaques and tangles," Pahan said.
https://www.sciencedaily.com/releases/2023/07/230722004622.htm
Volunteering in late life may protect the brain against cognitive decline and dementia
July 20, 2023
Science Daily/University of California - Davis Health
Volunteering in late life is associated with better cognitive function -- specifically, better executive function and episodic memory. Those are the findings of a new study from UC Davis Health presented today (July 20) at the Alzheimer's Association International Conference 2023 in Amsterdam.
"We hope these new data encourage individuals of all ages and backgrounds to engage in local volunteering -- not only to benefit their communities, but potentially their own cognitive and brain health," said Donna McCullough, Alzheimer's Association chief mission and field operations officer.
Volunteer activities -- such as supporting educational, religious, health-related or other charitable organizations -- allow older adults to be more physically active, increase social interaction and provide cognitive stimulation that may protect the brain. However, there has been a lack of information on the relationship between volunteering and cognitive function, especially in large, diverse populations.
Yi Lor, an epidemiology doctoral student at UC Davis, and Rachel Whitmer, the study's principal investigator, examined volunteering habits among an ethnic and racially diverse population of 2,476 older adults. The participants are in the Kaiser Healthy Aging and Diverse Life Experiences Study (KHANDLE) and the Study of Healthy Aging in African Americans (STAR).
The study group had an average age of 74 and contained 48% Black, 20% white, 17% Asian and 14% Latino participants. A total of 1,167 (43%) of the participants reported volunteering in the past year.
The researchers found that volunteering was associated with better baseline scores on tests of executive function and verbal episodic memory. This was true even after adjusting for age, sex, education, income, practice effects and interview mode (phone versus in-person).
Those who volunteered several times per week had the highest levels of executive function.
"Volunteering may be important for better cognition in late life and could serve as a simple intervention in all older adults to protect against risk for Alzheimer's disease and associated dementias," Lor said. "Our next steps are to examine whether volunteering is protective against cognitive impairment, and how physical and mental health may impact this relationship."
Volunteering was also associated with a trend toward less cognitive decline over the follow-up time of 1.2 years, but this association did not reach statistical significance.
"You're not in control of your family history or age -- you can't turn back the clock. But you are in control of how you spend your day and life," Whitmer said. "Volunteering is about keeping your brain active. It's also about socializing, which keeps you engaged and happy, and potentially lowers stress."
https://www.sciencedaily.com/releases/2023/07/230720124958.htm
Espresso can prevent Alzheimer's protein clumping in lab tests
July 19, 2023
Science Daily/American Chemical Society
Whether enjoyed on its own or mixed into a latte, Americano or even a martini, espresso provides an ultra-concentrated jolt of caffeine to coffee lovers. But it might do more than just wake you up. Research now published in ACS' Journal of Agricultural and Food Chemistry shows that, in preliminary in vitro laboratory tests, espresso compounds can inhibit tau protein aggregation -- a process that is believed to be involved in the onset of Alzheimer's disease.
Roughly half of all Americans drink coffee every day, and espresso is a popular way to consume it. To "pull" an espresso shot, hot water is forced through finely ground coffee beans, creating a concentrated extract. This is often used as a base for other drinks, including the trendy espresso martini. Recent research has suggested that coffee could also have beneficial effects against certain neurodegenerative diseases, including Alzheimer's disease. Although the exact mechanisms that cause these conditions are still unclear, it's thought that a protein called tau plays a significant role. In healthy people, tau proteins help stabilize structures in the brain, but when certain diseases develop, the proteins can clump together into fibrils. Some researchers propose that preventing this aggregation could alleviate symptoms. So, Mariapina D'Onofrio and colleagues wanted to see if compounds in espresso could prevent tau aggregation in vitro.
The researchers pulled espresso shots from store-bought beans, then characterized their chemical makeup using nuclear magnetic resonance spectroscopy. They chose caffeine and trigonelline, both alkaloids, the flavonoid genistein and theobromine, a compound also found in chocolate, to focus on in further experiments. These molecules, along with the complete espresso extract, were incubated alongside a shortened form of the tau protein for up to 40 hours. As the concentration of espresso extract, caffeine or genistein increased, fibrils were shorter and didn't form larger sheets, with the complete extract showing the most dramatic results. Shortened fibrils were found to be non-toxic to cells, and they did not act as "seeds" for further aggregation. In other experiments, the researchers observed that caffeine and the espresso extract could both bind pre-formed tau fibrils. Although much more research is needed, the team says that their preliminary in vitro findings could pave the way toward finding or designing other bioactive compounds against neurodegenerative diseases, including Alzheimer's.
https://www.sciencedaily.com/releases/2023/07/230719112644.htm
AI-guided brain stimulation aids memory in traumatic brain injury
July 18, 2023
Science Daily/University of Pennsylvania
AI-guided electrical stimulation in the brains of patients with traumatic brain injury improved memory, a collaborative new study shows. This builds on previous research involving epilepsy patients without traumatic brain injury. Brain injuries can result in profound memory loss, and the current study provides a proof-of-concept for future AI-guided brain stimulation therapies.
Traumatic brain injury (TBI) has disabled 1 to 2% of the population, and one of their most common disabilities is problems with short-term memory. Electrical stimulation has emerged as a viable tool to improve brain function in people with other neurological disorders.
Now, a new study in the journal Brain Stimulation shows that targeted electrical stimulation in patients with traumatic brain injury led to an average 19% boost in recalling words.
Led by University of Pennsylvania psychology professor Michael Jacob Kahana, a team of neuroscientists studied TBI patients with implanted electrodes, analyzed neural data as patients studied words, and used a machine learning algorithm to predict momentary memory lapses. Other lead authors included Wesleyan University psychology professor Youssef Ezzyat and Penn research scientist Paul Wanda.
"The last decade has seen tremendous advances in the use of brain stimulation as a therapy for several neurological and psychiatric disorders including epilepsy, Parkinson's disease, and depression," Kahana says. "Memory loss, however, represents a huge burden on society. We lack effective therapies for the 27 million Americans suffering."
Study co-author Ramon Diaz-Arrastia, director of the Traumatic Brain Injury Clinical Research Center at Penn Medicine, says the technology Kahana and his team developed delivers "the right stimulation at the right time, informed by the wiring of the individual's brain and that individual's successful memory retrieval."
He says the top causes of TBI are motor vehicle accidents, which are decreasing, and falls, which are rising because of the aging population. The next most common causes are assaults and head injuries from participation in contact sports.
This new study builds off the previous work of Ezzyat, Kahana, and their collaborators. Publishing their findings in 2017, they showed that stimulation delivered when memory is expected to fail can improve memory, whereas stimulation administered during periods of good functioning worsens memory. The stimulation in that study was open-loop, meaning it was applied by a computer without regard to the state of the brain.
In a study with 25 epilepsy patients that was published the following year, they monitored brain activity in real time and used closed-loop stimulation, applying electrical pulses to the left lateral temporal cortex only when memory was expected to fail. They found a 15% improvement in the probability of recalling a word from a list.
But the new study specifically focuses on eight people with a history of moderate-to-severe TBI, who were recruited from a larger group of patients undergoing neurosurgical evaluation for epilepsy. Seven of the eight are male, and Diaz-Arrastia says 80% of people who get hospitalized for traumatic brain injury overall are male.
Kahana emphasizes the importance of addressing TBI-related memory loss, noting, "These patients are often relatively young and physically healthy, but they face decades of impaired memory and executive function."
The researchers' primary question was whether stimulation could improve memory across entire lists of words when only some words were stimulated, whereas prior studies only considered the effect of stimulation on individual words. Ezzyat says this development is important because "this suggests that an eventual real-life therapy could provide more generalized memory improvement -- not just at the precise moment when stimulation is triggered."
The study notes that more work remains before this kind of stimulation can be applied in a therapeutic setting, and scientists need to study physiological responses to stimulation to better understand the neural mechanisms behind improved memory performance. Diaz-Arrastia says, "these are still early days in the field."
"I think eventually what we would need," he says, "is a self-contained, implantable system, where you could implant the electrodes into the brain of someone who had a brain injury."
https://www.sciencedaily.com/releases/2023/07/230718164310.htm
Those who are smarter live longer, at least among mouse lemurs
July 12, 2023
Science Daily/Deutsches Primatenzentrum (DPZ)/German Primate Center
Being smart pays off, as it allows for more balanced decision-making. However, the origins of these abilities during evolution remain largely unexplored. Only if smarter individuals enjoy better survival and have higher reproductive rates than their conspecifics, improved cognitive abilities can evolve. Researchers from the German Primate Center (DPZ) -- Leibniz Institute for Primate Research have recently examined the link between cognitive abilities and survival in gray mouse lemurs.
The study involved capturing the animals, subjecting them to various cognition and personality tests, measuring their weight, and subsequently releasing them. The findings revealed that the animals that performed best in the cognition tests lived for longer. Additionally, those that were heavier and displayed more exploratory behavior also experienced an increased lifespan. These results suggest that alternative strategies can contribute to an extended lifespan (Science Advances).
Cognitive abilities not only vary among different species but also among individuals within the same species. It is expected that smarter individuals live longer, as they are likely to make better decisions, regarding habitat and food selection, predator avoidance, and infant care. To investigate the factors influencing life expectancy of wild gray mouse lemurs, researchers from the German Primate Center conducted a long-term study in Madagascar.
They administered four different cognitive tests and two personality tests to 198 animals, while also measuring their weight and tracking their survival over several years. The cognition tests assessed problem-solving (reaching food by manipulating a slider), spatial memory (remembering the location of hidden food), inhibitory control (taking a detour to access food), and causal understanding (retrieving food by pulling a string). The first personality test evaluated exploratory behavior, while the second measured curiosity through the animals’ reactions to unfamiliar objects.
Either being particularly smart or particularly explorative – both strategies can lead to longer life
In the study, individuals that performed better in the cognitive tests exhibited less exploratory behavior compared to poorer performing conspecifics. Conversely, more explorative individuals had higher weights, likely due to their ability to find food more easily. The study also found that animals with better cognitive performance, higher weight, and stronger exploratory behavior tended to have longer lifespans. “These results suggest that being either smart or exhibiting good physical condition and exploratory behavior are likely to be different strategies that can lead to a longer lifespan,” said Claudia Fichtel, first author of the study and a scientist at the German Primate Center. “In future studies, we aim to investigate how cognitive abilities translate into behavioral strategies to find food or mating partner.”
https://www.sciencedaily.com/releases/2023/07/230712165127.htm
Those who are smarter live longer, at least among mouse lemurs
Social isolation linked to lower brain volume
July 12, 2023
Science Daily/American Academy of Neurology
Older people who have little social contact with others may be more likely to have loss of overall brain volume, and in areas of the brain affected by dementia, than people with more frequent social contact, according to a study published in the July 12, 2023, online issue of Neurology®, the medical journal of the American Academy of Neurology.
The study does not prove that social isolation causes brain shrinkage; it only shows an association.
"Social isolation is a growing problem for older adults," said study author Toshiharu Ninomiya, MD, PhD, of Kyushu University in Fukuoka, Japan. "These results suggest that providing support for people to help them start and maintain their connections to others may be beneficial for preventing brain atrophy and the development of dementia."
The study involved 8,896 people with an average age of 73 who did not have dementia. They had MRI brain scans and health exams. To determine social contact, people were asked one question: How often are you in contact with relatives or friends who do not live with you (e.g., meeting or talking on the phone)? The choices for answering were every day, several times a week, several times a month and seldom.
The people with the lowest amount of social contact had overall brain volume that was significantly lower than those with the most social contact. The total brain volume, or the sum of white and grey matter, as a percentage of the total intracranial volume, or the volume within the cranium, including the brain, meninges, and cerebrospinal fluid, was 67.3% in the lowest contact group compared to 67.8% in the highest contact group. They also had lower volumes in areas of the brain such as the hippocampus and amygdala that play a role in memory and are affected by dementia.
The researchers took into account other factors that could affect brain volume, such as age, diabetes, smoking and exercise.
The socially isolated people also had more small areas of damage in the brain, called white matter lesions, than the people with frequent social contact. The percentage of intracranial volume made up of white matter lesions was 0.30 for the socially isolated group, compared to 0.26 for the most socially connected group.
The researchers found that symptoms of depression partly explained the relationship between social isolation and brain volumes. However, symptoms of depression accounted for only 15% to 29% of the association.
"While this study is a snapshot in time and does not determine that social isolation causes brain atrophy, some studies have shown that exposing older people to socially stimulating groups stopped or even reversed declines in brain volume and improved thinking and memory skills, so it's possible that interventions to improve people's social isolation could prevent brain volume loss and the dementia that often follows," Ninomiya said.
Since the study involved only older Japanese people, a limitation is that the findings may not be generalizable to people of other ethnicities and younger people.
https://www.sciencedaily.com/releases/2023/07/230712165229.htm
Gum disease linked to buildup of Alzheimer's plaque formation
Oral bacteria traveling to the brain causes brain cells to become dysfunctional, promoting neuroinflammation
July 10, 2023
Science Daily/Forsyth Institute
Although most people don't associate oral disease with serious health problems, increasing evidence shows that oral bacteria play a significant role in systemic diseases like colon cancer and heart disease. Now, new research from the Forsyth Institute shows a link between periodontal (gum) disease and the formation of amyloid plaque, a hallmark of Alzheimer's disease.
In their paper, "Microglial cell response to experimental periodontal disease," published in the Journal of Neuroinflammation, Forsyth scientists and their collaborators at Boston University demonstrate that gum disease can lead to changes in brain cells called microglial cells, which are responsible for defending the brain from amyloid plaque. This plaque is a type of protein that is associated with cell death, and cognitive decline in people with Alzheimer's. The study provides important insight into how oral bacteria makes its way to the brain, and the role of neuroinflammation in Alzheimer's disease.
"We knew from one of our previous studies that inflammation associated with gum disease activates an inflammatory response in the brain," said Dr. Alpdogan Kantarci, senior member of staff at Forsyth and a senior author of the study. "In this study, we were asking the question, can oral bacteria cause a change in the brain cells?"
The microglial cells the researchers studied are a type of white blood cell responsible for digesting amyloid plaque. Forsyth scientists found that when exposed to oral bacteria the microglial cells became overstimulated and ate too much. "They basically became obese" Dr. Kantarci said. "They no longer could digest plaque formations."
The finding is significant for showing the impact of gum disease on systemic health. Gum disease causes lesions to develop between the gums and teeth. The area of this lesion is the size of your palm. Dr. Kantarci explained, "It's an open wound that allows the bacteria in your mouth to enter your bloodstream and circulate to other parts of your body." These bacteria can pass through the blood/brain barrier and stimulate the microglial cells in your brain.
Using mouse oral bacteria to cause gum disease in lab mice, the scientists were able to track periodontal disease progression in mice and confirm that the bacteria had traveled to the brain.
They then isolated the brain microglial cells and exposed them to the oral bacteria. This exposure stimulated the microglial cells, activated neuroinflammation and changed how microglial cells dealt with amyloid plaques.
"Recognizing how oral bacteria causes neuroinflammation will help us to develop much more targeted strategies," said Dr. Kantarci. "This study suggests that in order to prevent neuroinflammation and neurodegeneration, it will be critical to control the oral inflammation associated with periodontal disease. The mouth is part of the body and if you don't take care of oral inflammation and infection, you cannot really prevent systemic diseases, like Alzheimer's, in a reproducible way."
This study is the first time that scientists caused periodontal disease with mouse-specific bacteria and could study the effects of same-species oral microbiome on the brain. Having same-species bacteria and cells brings the test closer to replicating what the process looks like in humans.
https://www.sciencedaily.com/releases/2023/07/230710180512.htm
Fluctuating levels of cholesterol and triglycerides linked to increased risk of dementia
July 5, 2023
Science Daily/American Academy of Neurology
Older people who have fluctuating levels of cholesterol and triglycerides may have a higher risk of Alzheimer's disease and related dementias compared to people who have steady levels, according to new research published in the July 5, 2023, online issue of Neurology®, the medical journal of the American Academy of Neurology. While the study found a link, it does not prove that fluctuating levels of cholesterol and triglycerides cause dementia.
"Prevention strategies for Alzheimer's and related dementias are urgently needed," said study author Suzette J. Bielinski, PhD, of the Mayo Clinic in Rochester, Minnesota. "Routine screenings for cholesterol and triglyceride levels are commonly done as part of standard medical care. Fluctuations in these results over time could potentially help us identify who is at greater risk for dementia, help us understand mechanisms for the development of dementia and ultimately determine whether leveling out these fluctuations could play a role in reducing dementia risk."
Researchers used health care data to identify 11,571 people age 60 or older who did not have a prior diagnosis of Alzheimer's disease or dementia. Researchers looked at participants' measurements of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) on at least three different days in the five years before the start of the study.
Then researchers divided participants into five equal groups based on how much the measurements fluctuated. The lowest group had the least variation over time and the highest group had the most variation.
Participants were followed for an average of 13 years. During that time, 2,473 people developed Alzheimer's disease or another form of dementia.
After adjusting for variables that could affect risk of dementia including sex, race, education and lipid-lowering treatments, researchers found for total cholesterol, participants in the highest group had a 19% increased risk of dementia compared to those in the lowest group. Of the 2,311 people in the highest group, 515 developed dementia compared to 483 of the 2,311 people in the lowest group. For triglycerides, those in highest group had a 23% increased risk.
Researchers did not find a link between variations in LDL and HDL and an increased risk of dementia.
"It remains unclear why and how fluctuating levels of cholesterol and triglycerides are related to the risk of Alzheimer's disease," said Bielinski. "Further studies looking at the changes over time for this relationship are needed in order to confirm our results and potentially consider preventative strategies."
A limitation of the study was researchers looked at Alzheimer's disease and related dementias as a whole and did not differentiate between the types of dementia.
The study was supported by the National Heart, Lung and Blood Institute.
https://www.sciencedaily.com/releases/2023/07/230705171104.htm
Taking good care of your teeth may be good for your brain
Poor dental health linked to decline in brain volume
July 5, 2023
Science Daily/American Academy of Neurology
Taking good care of your teeth may be linked to better brain health, according to a study published in the July 5, 2023, online issue of Neurology®, the medical journal of the American Academy of Neurology. The study found that gum disease and tooth loss were linked to brain shrinkage in the hippocampus, which plays a role in memory and Alzheimer's disease. The study does not prove that gum disease or tooth loss causes Alzheimer's disease; it only shows an association.
"Tooth loss and gum disease, which is inflammation of the tissue around the teeth that can cause shrinkage of the gums and loosening of the teeth, are very common, so evaluating a potential link with dementia is incredibly important," said study author Satoshi Yamaguchi, PhD, DDS, of Tohoku University in Sendai, Japan. "Our study found that these conditions may play a role in the health of the brain area that controls thinking and memory, giving people another reason to take better care of their teeth."
The study involved 172 people with an average age of 67 who did not have memory problems at the beginning of the study.
Participants had dental exams and took memory tests at the beginning of the study. They also had brain scans to measure volume of the hippocampus at the beginning of the study and again four years later.
For each participant, researchers counted the number of teeth and checked for gum disease by looking at periodontal probing depth, a measurement of the gum tissue. Healthy readings are from one to three millimeters.
Mild gum disease involves probing depths of three or four millimeters in several areas, while severe gum disease involves probing depths of five or six millimeters in several areas as well as more bone loss and can cause teeth to become loose and eventually fall out.
Researchers found that the number of teeth and amount of gum disease was linked to changes in the left hippocampus of the brain.
For people with mild gum disease having fewer teeth was associated with a faster rate of brain shrinkage in the left hippocampus.
However, for people with severe gum disease having more teeth was associated with a faster rate of brain shrinkage in the same area of the brain.
After adjusting for age, researchers found that for people with mild gum disease, the increase in the rate of brain shrinkage due to one less tooth was equivalent to nearly one year of brain aging. Conversely, for people with severe gum disease the increase in brain shrinkage due to one more tooth was equivalent to 1.3 years of brain aging.
"These results highlight the importance of preserving the health of the teeth and not just retaining the teeth," Yamaguchi said. "The findings suggest that retaining teeth with severe gum disease is associated with brain atrophy. Controlling the progression of gum disease through regular dental visits is crucial, and teeth with severe gum disease may need to be extracted and replaced with appropriate prosthetic devices."
Yamaguchi said future studies are needed with larger groups of people. Another limitation of the study is that it was conducted in one region of Japan, so the results may not be generalizable to other locations.
https://www.sciencedaily.com/releases/2023/07/230705171101.htm
Regular napping linked to larger brain volume
Daytime napping may help to preserve brain health by slowing the rate at which our brains shrink as we age
June 20, 2023
Science Daily/University College London
A study analyzed data from people aged 40 to 69 and found a causal link between habitual napping and larger total brain volume -- a marker of good brain health linked to a lower risk of dementia and other diseases.
Daytime napping may help to preserve brain health by slowing the rate at which our brains shrink as we age, suggests a new study led by researchers at UCL and the University of the Republic in Uruguay.
The study, published in the journal Sleep Health, analysed data from people aged 40 to 69 and found a causal link between habitual napping and larger total brain volume -- a marker of good brain health linked to a lower risk of dementia and other diseases.
Senior author Dr Victoria Garfield (MRC Unit for Lifelong Health & Ageing at UCL) said: "Our findings suggest that, for some people, short daytime naps may be a part of the puzzle that could help preserve the health of the brain as we get older."
Previous research has shown that napping has cognitive benefits, with people who have had a short nap performing better in cognitive tests in the hours afterwards than counterparts who did not nap.
The new study aimed to establish if there was a causal relationship between daytime napping and brain health.
Using a technique called Mendelian randomisation, they looked at 97 snippets of DNA thought to determine people's likelihood of habitual napping. They compared measures of brain health and cognition of people who are more genetically "programmed" to nap with counterparts who did not have these genetic variants, using data from 378,932 people from the UK Biobank study, and found that, overall, people predetermined to nap had a larger total brain volume.
The research team estimated that the average difference in brain volume between people programmed to be habitual nappers and those who were not was equivalent to 2.6 to 6.5 years of ageing.
But the researchers did not find a difference in how well those programmed to be habitual nappers performed on three other measures of brain health and cognitive function -- hippocampal volume, reaction time and visual processing.
Lead author and PhD candidate Valentina Paz (University of the Republic (Uruguay) and MRC Unit for Lifelong Health & Ageing at UCL) said: "This is the first study to attempt to untangle the causal relationship between habitual daytime napping and cognitive and structural brain outcomes. By looking at genes set at birth, Mendelian randomisation avoids confounding factors occurring throughout life that may influence associations between napping and health outcomes. Our study points to a causal link between habitual napping and larger total brain volume."
Dr Garfield added: "I hope studies such as this one showing the health benefits of short naps can help to reduce any stigma that still exists around daytime napping."
The genetic variants influencing our likelihood to nap were identified in an earlier study looking at data from 452,633 UK Biobank participants. The study, led by Dr Hassan Dashti (Harvard University and Massachusetts General Hospital), also an author on the new study, identified the variants on the basis of self-reported napping, and this was supported by objective measurements of physical activity recorded by a wrist-worn accelerometer.
In the new study, researchers analysed health and cognition outcomes for people with these genetic variants as well as several different subsets of these variants, adjusted to avoid potential bias, for instance avoiding variants linked to excessive daytime sleepiness.
Genetic data and magnetic resonance imaging (MRI) scans of the brain were available for 35,080 individuals drawn from the larger UK Biobank sample.
In terms of study limitations, the authors noted that all of the participants were of white European ancestry, so the findings might not be immediately generalisable to other ethnicities.
While the researchers did not have information on nap duration, earlier studies suggest that naps of 30 minutes or less provide the best short-term cognitive benefits, and napping earlier in the day is less likely to disrupt night-time sleep.
Previous research looking at the UK and the Netherlands found that nearly a third of adults aged 65 or over had a regular nap.
https://www.sciencedaily.com/releases/2023/06/230620113759.htm
'Smart' drugs can decrease productivity in people who don't have ADHD
June 14, 2023
Science Daily/University of Cambridge
Research suggests that complex tasks akin to real life decision-making take neurotypical people longer to complete when they take 'smart' drugs than when they do not. The smart drugs do motivate people, but the added effort can lead to 'erratic thinking,' adversely affecting above-average performers.
New research from the University of Cambridge and the University of Melbourne, published in Science Advances, shows neurotypical workers and students taking cognitive enhancers, or 'smart' drugs, may actually be inhibiting their performance and productivity.
Drugs such as methylphenidate, sold under the brand name Ritalin among others, are commonly prescribed for attention deficit hyperactivity disorder (ADHD), but are also taken by those without a diagnosis, in the belief that the drugs will enhance focus and cognitive performance.
In four double-blinded, randomised trials in Melbourne, each a week apart, the same 40 healthy participants took one of three popular 'smart' drugs (methylphenidate, modafinil or dextroamphetamine) or a placebo. They were assessed on how they performed in a test designed to model the complex decision-making and problem-solving present in our everyday lives.
While previous studies into the effects of smart drugs have used simpler cognitive tasks targeting memory or attention, the Melbourne trial involved more computationally complex activities that better simulate the difficult nature of tasks people encounter in daily life.
Participants were asked to complete an exercise known as the Knapsack Optimisation Problem -- or 'knapsack task' -- in which they were given a virtual knapsack with a set capacity, and a selection of items of different weights and values. The participants had to figure out how to best allocate items to the bag, to maximise the overall value of its contents.
Overall, participants taking the drugs saw small decreases in accuracy and efficiency, along with large increases in time and effort, relative to their results when not taking the drugs.
For example, when given methylphenidate -- often used to treat ADHD in children, but increasingly taken by college students cramming for exams -- participants took around 50% longer on average to complete the knapsack problem as when they were given a placebo.
In addition, participants who performed at a higher level in the placebo condition compared to the rest of the group tended to show a bigger decrease in performance and productivity after receiving a drug.
In terms of "productivity," for example -- the level of progress per item moved in or out of the knapsack -- the participants in the top 25% under a placebo regularly ended up in the bottom 25% under methylphenidate.
By contrast, participants who had a lower performance in a placebo condition only very occasionally exhibited a slight improvement after taking a drug.
Professor Peter Bossaerts, Leverhulme International Professor of Neuroeonomics at the University of Cambridge, believes more research needs to be conducted to find out what effects the drugs are having on users without ADHD.
"Our results suggest that these drugs don't actually make you 'smarter'," said Bossaerts. "Because of the dopamine the drugs induce, we expected to see increased motivation, and they do motivate one to try harder. However, we discovered that this exertion caused more erratic thinking -- in ways that we could make precise because the knapsack task had been widely studied in computer science.
"Performance did not generally increase, so questions remain about how the drugs are affecting people's minds and their decision making."
Dr Elizabeth Bowman researcher at the Centre for Brain, Mind and Markets at the University of Melbourne and lead author of the study said the results show we have yet to establish the effectiveness of pharmaceutical enhancers on our performance, when used by neurotypical people to perform everyday complex tasks.
"Our research shows drugs that are expected to improve cognitive performance in patients may actually be leading to healthy users working harder while producing a lower quality of work in a longer amount of time," said Bowman.
https://www.sciencedaily.com/releases/2023/06/230614220559.htm
Altered gut bacteria may be early sign of Alzheimer's disease
Gut microbes of people with pre-symptomatic Alzheimer's differ from those of healthy people
June 14, 2023
Science Daily/Washington University School of Medicine
Alzheimer's disease causes changes to the brain that begin two decades or more before symptoms appear. A study reveals that the bacteria that live in the gut also change before Alzheimer's symptoms arise, a discovery that could lead to diagnostics or treatments for Alzheimer's disease that target the gut microbiome.
People in the earliest stage of Alzheimer's disease -- after brain changes have begun but before cognitive symptoms become apparent -- harbor an assortment of bacteria in their intestines that differs from the gut bacteria of healthy people, according to a study by researchers at Washington University School of Medicine in St. Louis.
The findings, published June 14 in Science Translational Medicine, open up the possibility of analyzing the gut bacterial community to identify people at higher risk of developing dementia, and of designing microbiome-altering preventive treatments to stave off cognitive decline.
"We don't yet know whether the gut is influencing the brain or the brain is influencing the gut, but this association is valuable to know in either case," said co-corresponding author Gautam Dantas, PhD, the Conan Professor of Laboratory and Genomic Medicine. "It could be that the changes in the gut microbiome are just a readout of pathological changes in the brain. The other alternative is that the gut microbiome is contributing to Alzheimer's disease, in which case altering the gut microbiome with probiotics or fecal transfers might help change the course of the disease."
The idea of studying the connection between the gut microbiome and Alzheimer's disease came together at a youth soccer game, where Dantas and Beau M. Ances, MD, PhD, the Daniel J. Brennan Professor of Neurology, chatted while their children played. Ances treats and studies people with Alzheimer's disease; Dantas is an expert on the gut microbiome.
Scientists already knew that the gut microbiomes of people with symptomatic Alzheimer's differ from the microbiomes of healthy people of the same age. But, Ances told Dantas, nobody had yet looked at the gut microbiomes of people in the critical pre-symptomatic phase.
"By the time people have cognitive symptoms, there are significant changes that are often irreversible," said Ances, the other co-corresponding author. "But if you can diagnosis someone very early in the disease process, that would be the optimal time to effectively intervene with a therapy."
During the early stage of Alzheimer's disease, which can last two decades or more, affected people accumulate clumps of the proteins amyloid beta and tau in their brains, but do not exhibit signs of neurodegeneration or cognitive decline.
Dantas, Ances and first author Aura L. Ferreiro, PhD, then a graduate student in Dantas' lab and now a postdoctoral researcher, evaluated participants who volunteer for studies at the Charles F. and Joanne Knight Alzheimer Disease Research Center at Washington University. All participants were cognitively normal. As part of this study, participants provided stool, blood and cerebrospinal fluid samples; kept food diaries; and underwent PET and MRI brain scans.
To distinguish participants already in the early stage of Alzheimer's disease from those who were healthy, the researchers looked for signs of amyloid beta and tau accumulation through brain scans and cerebrospinal fluid. Of the 164 participants, about a third (49) had signs of early Alzheimer's.
An analysis revealed that healthy people and people with preclinical Alzheimer's disease have markedly different gut bacteria -- in terms of the species of bacteria present and the biological processes in which those bacteria are involved -- despite eating basically the same diet. These differences correlated with amyloid and tau levels, which rise before cognitive symptoms appear, but did not correlate with neurodegeneration, which becomes evident about the time cognitive skills start to decline. These differences potentially could be used to screen for early Alzheimer's disease, the researchers said.
"The nice thing about using the gut microbiome as a screening tool is its simplicity and ease," Ances said. "One day individuals may be able to provide a stool sample and find out if they are at increased risk for developing Alzheimer's disease. It would be much easier and less invasive and more accessible for a large proportion of the population, especially underrepresented groups, compared to brain scans or spinal taps."
The researchers have launched a five-year follow-up study designed to figure out whether the differences in the gut microbiome are a cause or a result of the brain changes seen in early Alzheimer's disease.
"If there is a causative link, most likely the link would be inflammatory," said Dantas, who is also a professor of pathology & immunology, of biomedical engineering, of molecular microbiology and of pediatrics. "Bacteria are these amazing chemical factories, and some of their metabolites affect inflammation in the gut or even get into the bloodstream, where they can influence the immune system all over the body. All of this is speculative at this point, but if it turns out that there is a causal link, we can start thinking about whether promoting 'good' bacteria or getting rid of 'bad' bacteria could slow down or even stop the development of symptomatic Alzheimer's disease."
https://www.sciencedaily.com/releases/2023/06/230614220554.htm
Entrepreneurs' brains: Researchers reveal increased cognitive flexibility
A pioneering and multidisciplinary study involving serial entrepreneurs and managers found evidence of increased neuronal connectivity in the brains of entrepreneurs, which may contribute to distinct cognitive attributes
June 13, 2023
Science Daily/University of Liege
In a pioneering study involving serial entrepreneurs and managers, a multidisciplinary research team led by HEC -- School of Management at the University of Liège and Liège University Hospital (CHU Liège), combining entrepreneurship researchers and brain specialists, found evidence of increased neuronal connectivity in the brains of entrepreneurs, which may contribute to distinct cognitive attributes.
Using resting-state functional magnetic resonance imaging (rs-fMRI), the study showed that serial entrepreneurs have higher connectivity between the right insula (associated with cognitive flexibility) and the anterior prefrontal cortex (a key region for exploratory choices), compared to their fellow managers. These results, published in the journal Entrepreneurship Theory and Practice, suggest that serial entrepreneurs possess greater cognitive flexibility, enabling them to alternate effectively between exploration and exploitation, a balance that is crucial to their success.
Unlike the traditional fMRI approach based on tasks submitted to the subject, the rs-fMRI on which this study is based observes the brain at rest, in the absence of cognitive tasks or presentation of stimuli, which constitutes an innovative approach to improving understanding of the entrepreneurial mind. Forty people, entrepreneurs and managers, took part in the study.
"This study represents an important advance in our understanding of the entrepreneurial mind. It highlights the potential of neuroscience and how this approach complements the traditional tools used to study entrepreneurial cognition. By highlighting the difference in cognitive flexibility, it also offers a new perspective to inform the design of training or professional development programmes aimed at improving the cognitive flexibility and entrepreneurial spirit of individuals within various organisations," explains Frédéric Ooms, researcher and Assistant Professor in management and entrepreneurship (HEC -- ULiège School of Management), first author of the publication, based on the results of his PhD thesis on entrepreneurial cognitive flexibility presented in April 2023.
"In a world of rapid and unpredictable change, organisations need to cultivate an entrepreneurial mindset and foster cognitive flexibility within their teams, qualities recognised by the OECD as a 21st century challenge," points out Professor Bernard Surlemont, Professor of Entrepreneurship at ULiège (HEC Liège).
https://www.sciencedaily.com/releases/2023/06/230613110035.htm
How does dopamine regulate both learning and motivation?
June 6, 2023
Science Daily/Netherlands Institute for Neuroscience - KNAW
A new study from the Netherlands Institute for Neuroscience brings together two schools of thought on the function of the neurotransmitter dopamine: one saying that dopamine provides a learning signal, the other saying that dopamine drives motivation. 'But it is probably both', says Ingo Willuhn.
It is well-known that the dopamine system is implicated in signaling reward-related information as well as in actions that generate rewarding outcomes. This can be investigated using either Pavlovian and operant conditioning experiments. Pavlovian conditioning describes how your brain makes an association between two situations or stimuli that previously seemed unrelated. A famous example is Pavlov's experiment, where a dog heard a sound before receiving food. After several such pairings of the sound with food delivery, the sound alone began to cause the dog to salivate. Operant conditioning, or instrumental learning, differs from this in that the behavior of an individual is important to earn a food reward. Meaning that the individual after hearing a sound, has to perform a so-called operant action to receive the reward. In animal experiments, such a operant response is often the pressing of a lever.
Dopamine measurements in nucleus accumbens
In the final PhD paper of Jessica Goedhoop in collaboration with Tara Arbab and Ingo Willuhn from the Netherlands Institute for Neuroscience, they take a closer look at the role of dopamine signaling in learning and motivation. The team directly compared the two conditioning paradigms: male rats underwent either Pavlovian or operant conditioning while dopamine release was measured in the nucleus accumbens, a brain region central for processing this information. During the experiments a cue light was illuminated for a duration of 5 seconds. For the Pavlovian group, a food pellet was delivered into the reward magazine directly after the cue light turned off. For the operant conditioning group, turning off the cue light was followed by extension of the lever below the cue light into the operant box. The lever was retracted after one lever press, which immediately resulted in the delivery of one food pellet reward into the food magazine. If there was no lever press within 5 seconds after lever extension, the lever was retracted and no reward was delivered.
Sustained dopamine release in operant conditioning
Rats in both groups released the same quantity of dopamine at the onset of the reward-predictive cue. However, only the operant-conditioning group showed a subsequent, sustained plateau in dopamine concentration throughout the entire 5-second cue presentation (throughout cue presentation and before lever press). This dopamine sustainment was observed reliably and consistently throughout systematic manipulation of experimental parameters and behavioral training. Therefore, the researchers believe that sustained dopamine levels may be an intermediate between learning and action, conceptually related to the motivation to generate a reward-achieving action.
Ingo Willuhn: 'There have been a lot of studies on dopamine. We have a decent idea of when dopamine is released in the brain, but there is still lots of discussion on what the precise variables are that determine such dopamine signaling. Essentially discussion on what dopamine "means." To investigate this, scientists usually perform either Pavlovian or operant conditioning experiments. But they test slightly different things. Both have to do with learning an association between a neutral stimulus and a reward. But operant conditioning requires the motivation to perform an action in addition to that (to earn the reward). Therefore, we compared the two types of conditioning in the same experiment.'
Adding a piece to the puzzle
'Our results bring together the two camps of scientists that often battle with each other: one says that dopamine is a so-called reward-prediction error signal, meaning that dopamine is released when something better than expected happens, and is suppressed when something worse than expected happens. It is a learning (or teaching) signal. The other camp says that this is not true. They say that dopamine has something to do with motivation. Increased dopamine release will invigorate the subjects and they work harder to get the reward. There have been a few attempts in the past to bring these two camps together, but there is still need for more knowledge on the subject.'
'What we saw in our study is that only in the operant-learning task dopamine levels stayed high. It seems that the motivation is encoded in this plateau. Reward prediction is the initial dopamine peak, but how much the signal stays up, reflects motivation. Thus, our paper suggests that there is a possibility that dopamine is involved in both, learning and motivation. The next steps will be to get more details out of this. We need to replicate the experiments and make them more sophisticated. The more sophisticated you make it, the more precise our predictions have to be. We are going to build on it and see whether it still holds up.'
Implications
'Dopamine is not only involved in everyday life but also in disorders such as addiction, Parkinson's disease, and schizophrenia. Because of the two camps existing, there is disagreement about what happens exactly. For example, some researchers say that when addicts take drugs dopamine release increases and as a consequence all the environmental cues become more meaningful. Addicts learn that these cues are associated with the drug and they take more and more drug, because they are constantly reminded of the drug everywhere. In this view, addiction is misguided learning. Other researchers would say that motivation to take the drug intensifies with more frequent drug intake, because the drug elevates dopamine release. This study indicates that it may be both. Depending on the precise timing, both systems could be the driver, and both could be involved.'
'This is also relevant for the clinic. Prescribed drugs can influence both learning and motivation systems at the same time: and then it can get messy. If you give schizophrenic patients classic antipsychotic medication, they become slow and cannot act much because their motivation system is down. Parkinson's patients take pro-dopamine drugs essentially because they lost their dopamine, but some patients start to gamble because their dopamine system is on overdrive suddenly. We cannot influence learning and motivation components separately. As soon as you give a drug it is going to hit all of it, so it is good to keep that in mind.'
https://www.sciencedaily.com/releases/2023/06/230606111734.htm