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Summary: A new study reveals a single neuron is capable of encoding information from two different sounds by switching between signals associated with one sound to that of the other.

Source: Duke University.

Back in the early days of telecommunications, engineers devised a clever way to send multiple telephone calls through a single wire at the same time. Called time-division multiplexing, this technique rapidly switches between sending pieces of each message.

New research from Duke University shows that neurons in the brain may be capable of a similar strategy.

In an experiment examining how monkeys respond to sound, a team of neuroscientists and statisticians found that a single neuron can encode information from two different sounds by switching between the signal associated with one sound and the signal associated with the other sound.

“The question we asked is, how do neurons preserve information about two different stimuli in the world at one time?” said Jennifer Groh, professor in the department of psychology and neuroscience, and in the department of neurobiology at Duke.

“We found that there are periods of time when a given neuron responds to one stimulus, and other periods of time where it responds to the other,” Groh said. “They seem to be able to alternate between each one.”

The results may explain how the brain processes complex information from the world around us, and may also provide insight into some of our perceptual and cognitive limitations. The results appeared July 13 in Nature Communications.

To make the discovery, Groh and her team collaborated with Surya Tokdar, associate professor of statistical science at Duke, to develop and apply several new methods of analysis to their experimental data.

Most studies of single neuron behavior investigate only one stimulus at a time, looking at how an individual neuron responds when the subject is played a single note or shown a single image.

But reality is rarely so simple. Our brains are capable of processing multiple stimuli at once — such as listening to a friend at a party with music playing in the background, or picking out the buzz of a cicada from a symphony of trilling insects.

“It is not obvious how you go from single neurons encoding single objects, to neurons encoding multiple objects,” said Valeria Caruso, a research scientist in Duke’s department of psychology and neuroscience. “We wanted to provide an intermediate step, looking at how neurons encode small groups of objects.”

To complicate matters, single-neuron studies have shown that many sensory neurons are broadly tuned, meaning each is capable of responding to sounds at a range of different frequencies. For example, the same neurons triggered by your friend’s voice may also be triggered by the notes of your favorite tunes.

“If I am a neuron and I’m able to respond to both an image of a pillow and the couch it is resting on, how does the brain infer that both the pillow and the couch are present?” Groh said.

In the experiment, the researchers sat monkeys in a darkened room and trained them to look in the direction of sounds that they heard. The researchers played either one sound or two sounds, with each sound at a different frequency and coming from different locations.

When the researchers played two sounds together, the monkeys looked first in the direction of one sound, and then in the direction of the other sound, indicating that the monkeys recognized the existence of two distinct sounds.

To find out how the monkeys’ brains encoded both sounds simultaneously, the team used electrodes in the inferior colliculus, a key point in the brain’s auditory pathway, to measure the small spikes in the local electric field caused by neurons firing.

The researchers investigated the response of single neurons to both individual sounds and to combined sounds. The standard practice in the field is to count how many spikes occur over a period of time and compute the average of a number of trials, Groh said. But this method obscures any fluctuations in activity that might indicate the neurons are switching back and forth between different stimuli.

The team applied a combination of advanced statistical methods, including a new method called a Dynamic Admixture Point Process model developed by Tokdar and his team, to extract more detailed patterns from the data.

They found that a single neuron could respond to one sound with one firing rate, and a second sound with a different firing rate. When both sounds were played simultaneously, it appeared to fluctuate between the two firing rates. Sometimes the fluctuations were fast enough that the neurons switched within a half second of the presentation of the sound, and in other cases the switching was slower.

The team repeated the statistical analysis on data from experiments conducted by Winrich Freiwald, a professor of neurosciences and behavior at The Rockefeller University. In these experiments, Freiwald investigated the firing rates of single neurons in a visual area of the cortex in response to images of one face or two faces. The analysis revealed the same switching pattern when two faces were present.

These findings provide clues to other circumstances where the brain has to do more than one thing at a time with a limited set of neurons. For example, our working memory — the number of things we can hold in our minds at one time — is constrained to around five to seven items. While these experiments do not directly test working memory, the researchers think further studies may help explain these restrictions.

“Our working memory system is quite limited and no one really knows why,” Groh said. “Perhaps that limit arises from some kind of cycling behavior where you are coding one thing at a time, and across a period of time, the number of things you can represent depends on how long you need to represent each one and how rapidly you can switch.”

Funding: This research was supported by the National Science Foundation (0924750), and the National Institutes of Health (5R01DC013906-02).

Source: Kara Manke – Duke University
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is credited to Cruger Creations.
Original Research: Open access research for “Single neurons may encode simultaneous stimuli by switching between activity patterns” by Valeria C. Caruso, Jeff T. Mohl, Christopher Glynn, Jungah Lee, Shawn M. Willett, Azeem Zaman, Akinori F. Ebihara, Rolando Estrada, Winrich A. Freiwald, Surya T. Tokdar & Jennifer M. Groh in Nature Communications. Published July 13 2018.
doi:10.1038/s41467-018-05121-8

Abstract

Single neurons may encode simultaneous stimuli by switching between activity patterns

How the brain preserves information about multiple simultaneous items is poorly understood. We report that single neurons can represent multiple stimuli by interleaving signals across time. We record single units in an auditory region, the inferior colliculus, while monkeys localize 1 or 2 simultaneous sounds. During dual-sound trials, we find that some neurons fluctuate between firing rates observed for each single sound, either on a whole-trial or on a sub-trial timescale. These fluctuations are correlated in pairs of neurons, can be predicted by the state of local field potentials prior to sound onset, and, in one monkey, can predict which sound will be reported first. We find corroborating evidence of fluctuating activity patterns in a separate dataset involving responses of inferotemporal cortex neurons to multiple visual stimuli. Alternation between activity patterns corresponding to each of multiple items may therefore be a general strategy to enhance the brain processing capacity, potentially linking such disparate phenomena as variable neural firing, neural oscillations, and limits in attentional/memory capacity.

Summary: Researchers have successfully identified autism risk in young mice by examining their mother’s microbiome during pregnancy. The study, which may offer the earliest detection of autism, could pave the way to developing preventative measures against forms of autism by altering the maternal diet and probiotic intake.

Source: University of Virginia Health System.

The risk of developing autism-spectrum disorders is determined by the mother’s microbiome – the collection of microorganisms that naturally live inside us – during pregnancy, new research from the University of Virginia School of Medicine suggests. The work raises the possibility that preventing forms of autism could be as simple as an expectant mom modifying her diet or taking custom probiotics.

Further, the UVA scientists were able to use their discovery to prevent the development of autism-like neurodevelopmental disorders in lab mice. They found they could halt the development of such disorders by blocking a particular inflammatory molecule produced by the immune system. Targeting this molecule, interleukin-17a, offers another potential avenue for preventing autism in people, the researchers say. They caution, however, that this approach would be much more complex because of the risk of side effects.

“We determined that the microbiome is a key contributor in determining susceptibility [to autism-like disorders], so it suggests that you could target either the maternal microbiome or this inflammatory molecule, IL-17a,” said lead researcher John Lukens, PhD, of UVA’s Department of Neuroscience. “You could also use this [IL-17a] as a biomarker for early diagnosis.”

Microbiome and Autism

The groundbreaking work from Lukens and his colleagues sheds light on the complex relationship between the health of the mother’s microbiome and the healthy development of her children. “The microbiome can shape the developing brain in multiple ways,” explained Lukens, of UVA’s Center for Brain Immunology and Glia (BIG) and UVA’s Carter Immunology Center. “The microbiome is really important to the calibration of how the offspring’s immune system is going to respond to an infection or injury or stress.”

But an unhealthy microbiome in the mom can create problems: Lukens’ work shows that it can make her unborn offspring susceptible to neurodevelopmental disorders. The researchers found that the IL-17a molecule was a key contributor to the development of autism-like symptoms in lab mice.

The good news: The microbiome can be modified easily, either through diet, probiotic supplements or fecal transplant. All of these approaches seek to restore a healthy equilibrium among the different microorganisms that live in the gut.

“In terms of translating our work to humans, I think the next big step would be to identify features of the microbiome in pregnant mothers that correlate with autism risk,” Lukens said. “I think the really important thing is to figure out what kind of things can be used to modulate the microbiome in the mother as effectively and safely as we can.”

Another Option for Preventing Autism

Blocking IL-17a also might offer a way to prevent autism, but Lukens said that path carries much more risk. “If you think about pregnancy, the body is basically accepting foreign tissue, which is a baby,” he said. “As a result, maintenance of embryonic health demands a complex balance of immune regulation, so people tend to shy away from manipulating the immune system during pregnancy.”

IL-17a previously has been implicated in conditions such as rheumatoid arthritis, multiple sclerosis and psoriasis, and there are already drugs available that target it. But Lukens noted that the molecule has an important purpose in stopping infections, especially fungal infections. Blocking it, he said, “could make you susceptible to all kinds of infections.” And doing so during pregnancy could have complex ripple effects on a child’s development that scientists would need to sort out.

For their next steps, Lukens and his team plan to explore the potential role of other immune molecules in the development of autism and other such conditions. IL-17a may be just one piece in a much larger puzzle, he said.

While Lukens’ work links the immune system with neurodevelopmental disorders, he emphasized that this in no way suggests that vaccines are contributing to the development of autism. “There’s a definite link between the immune response and the developing brain,” he said. “It just doesn’t have anything to do with vaccines. It’s much, much earlier.”

Lukens’ work is but the latest research from UVA to speak to the importance of the microbiome in maintaining good health. For example, one of Lukens’ colleagues in the Department of Neuroscience, Alban Gaultier, PhD, found that probiotics in yogurt can reverse depression symptoms.

Funding: The work was supported by the Hartwell Foundation, the Owens Family Foundation and the Simons Foundation Autism Research Initiative. In addition, members of the research team received support from the National Institutes of Health/National Institute of General Medical Sciences, UVA’s Medical Scientist Training Program and from Hutcheson and Stull Undergraduate Research Fellowships.

Source: Josh Barney – University of Virginia Health System
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is credited to Alexandra N. Angelich | University of Virginia Communications.
Original Research: Abstract for “Cutting Edge: Critical Roles for Microbiota-Mediated Regulation of the Immune System in a Prenatal Immune Activation Model of Autism” by Catherine R. Lammert, Elizabeth L. Frost, Ashley C. Bolte, Matt J. Paysour, Mariah E. Shaw, Calli E. Bellinger, Thaddeus K. Weigel, Eli R. Zunder and John R. Lukens in Journal of Immunology. Published July 2 2018.
doi:10.4049/jimmunol.1701755

Abstract

Cutting Edge: Critical Roles for Microbiota-Mediated Regulation of the Immune System in a Prenatal Immune Activation Model of Autism

Recent studies suggest that autism is often associated with dysregulated immune responses and altered microbiota composition. This has led to growing speculation about potential roles for hyperactive immune responses and the microbiome in autism. Yet how microbiome–immune cross-talk contributes to neurodevelopmental disorders currently remains poorly understood. In this study, we report critical roles for prenatal microbiota composition in the development of behavioral abnormalities in a murine maternal immune activation (MIA) model of autism that is driven by the viral mimetic polyinosinic-polycytidylic acid. We show that preconception microbiota transplantation can transfer susceptibility to MIA-associated neurodevelopmental disease and that this is associated with modulation of the maternal immune response. Furthermore, we find that ablation of IL-17a signaling provides protection against the development of neurodevelopmental abnormalities in MIA offspring. Our findings suggest that microbiota landscape can influence MIA-induced neurodevelopmental disease pathogenesis and that this occurs as a result of microflora-associated calibration of gestational IL-17a responses.

Source: University of Warwick.

Sugar improves memory in older adults – and makes them more motivated to perform difficult tasks at full capacity – according to new research by the University of Warwick.

Led by PhD student Konstantinos Mantantzis, Professor Elizabeth Maylor and Dr Friederike Schlaghecken in Warwick’s Department of Psychology, the study found that increasing blood sugar levels not only improves memory and performance, but makes older adults feel happier during a task.

The researchers gave young (aged 18-27) and older (aged 65-82) participants a drink containing a small amount of glucose, and got them to perform various memory tasks. Other participants were given a placebo – a drink containing artificial sweetener.

The researchers measured participants’ levels of engagement with the task, their memory score, mood, and their own perception of effort.

They found that increasing energy through a glucose drink can help both young and older adults to try harder compared to those who had the artificial sweetener. For young adults, that’s where it ended, though: glucose did not improve either their mood or their memory performance.

However, older adults who had a glucose drink showed significantly better memory and more positive mood compared to older adults who consumed the artificial sweetener.

Moreover, although objective measures of task engagement showed that older adults in the glucose group put more effort into the task than those who consumed the artificial sweetener, their own self-reports showed that they did not feel as if they had tried any harder.

The authors concluded that short-term energy availability in the form of raised blood sugar levels could be an important factor in older adults’ motivation to perform a task at their highest capacity.

Heightened motivation, in turn, could explain the fact that increased blood sugar levels also increase older adults’ sense of self-confidence, decrease self-perceptions of effort, and improve mood. However, more research is needed to disentangle these factors in order to fully understand how energy availability affects cognitive engagement, and to develop clear dietary guidelines for older adults.

Konstantinos Mantantzis, a PhD student from the University of Warwick’s Department of Psychology, commented:

“Over the years, studies have shown that actively engaging with difficult cognitive tasks is a prerequisite for the maintenance of cognitive health in older age. Therefore, the implications of uncovering the mechanisms that determine older adults’ levels of engagement cannot be understated.”

Dr Friederike Schlaghecken, from the University of Warwick’s Department of Psychology, commented:

“Our results bring us a step closer to understanding what motivates older adults to exert effort and finding ways of increasing their willingness to try hard even if a task seems impossible to perform.”

It is co-authored by PhD student Konstantinos Mantantzis, Professor Elizabeth Maylor and Dr Friederike Schlaghecken at the University of Warwick, UK.

Source: Luke Walton – University of Warwick
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Abstract for “Gain without pain: Glucose promotes cognitive engagement and protects positive affect in older adults” by Mantantzis, Konstantinos; Maylor, Elizabeth A.; and Schlaghecken, Friederike in Psychology and Aging. Published July 12 2018.
doi:10.1037/pag0000270

Abstract

Gain without pain: Glucose promotes cognitive engagement and protects positive affect in older adults

When faced with a cognitively demanding task, older adults tend to disengage and withdraw effort. At the same time, their usual processing preference for positive information disappears. Providing glucose as an energy resource is known to improve cognitive performance and reinstate older adults’ positivity preference. Here, we examined whether glucose can help older adults to exert more effort under high difficulty conditions, and if so, whether such increase is accompanied by a change in positive affect. Fifty-three young and 58 older adults consumed a glucose or a placebo drink and completed a memory-search task at three levels of difficulty. Cognitive engagement was measured through changes in heart rate (HR) and self-reported effort. After each memory-search block, participants completed an implicit emotion-assessment task. In both age groups, glucose produced increased HR (indicating higher task engagement) relative to placebo. In older but not in young adults, glucose also improved cognitive performance and increased positive affect. Subjective effort, in contrast, did not differ between the older-glucose and older-placebo groups. These results suggest that in older adults, glucose improves cognitive performance by promoting higher cognitive engagement while mitigating the subjective costs of effortful exertion.

Summary: Increasing blood sugar levels in those over 60 helps improve memory and performance, a new study reports.

Source: University of Warwick.

Sugar improves memory in older adults – and makes them more motivated to perform difficult tasks at full capacity – according to new research by the University of Warwick.

Led by PhD student Konstantinos Mantantzis, Professor Elizabeth Maylor and Dr Friederike Schlaghecken in Warwick’s Department of Psychology, the study found that increasing blood sugar levels not only improves memory and performance, but makes older adults feel happier during a task.

The researchers gave young (aged 18-27) and older (aged 65-82) participants a drink containing a small amount of glucose, and got them to perform various memory tasks. Other participants were given a placebo – a drink containing artificial sweetener.

The researchers measured participants’ levels of engagement with the task, their memory score, mood, and their own perception of effort.

They found that increasing energy through a glucose drink can help both young and older adults to try harder compared to those who had the artificial sweetener. For young adults, that’s where it ended, though: glucose did not improve either their mood or their memory performance.

However, older adults who had a glucose drink showed significantly better memory and more positive mood compared to older adults who consumed the artificial sweetener.

Moreover, although objective measures of task engagement showed that older adults in the glucose group put more effort into the task than those who consumed the artificial sweetener, their own self-reports showed that they did not feel as if they had tried any harder.

The authors concluded that short-term energy availability in the form of raised blood sugar levels could be an important factor in older adults’ motivation to perform a task at their highest capacity.

Heightened motivation, in turn, could explain the fact that increased blood sugar levels also increase older adults’ sense of self-confidence, decrease self-perceptions of effort, and improve mood. However, more research is needed to disentangle these factors in order to fully understand how energy availability affects cognitive engagement, and to develop clear dietary guidelines for older adults.

Konstantinos Mantantzis, a PhD student from the University of Warwick’s Department of Psychology, commented:

“Over the years, studies have shown that actively engaging with difficult cognitive tasks is a prerequisite for the maintenance of cognitive health in older age. Therefore, the implications of uncovering the mechanisms that determine older adults’ levels of engagement cannot be understated.”

Dr Friederike Schlaghecken, from the University of Warwick’s Department of Psychology, commented:

“Our results bring us a step closer to understanding what motivates older adults to exert effort and finding ways of increasing their willingness to try hard even if a task seems impossible to perform.”

It is co-authored by PhD student Konstantinos Mantantzis, Professor Elizabeth Maylor and Dr Friederike Schlaghecken at the University of Warwick, UK.

Source: Luke Walton – University of Warwick
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Abstract for “Gain without pain: Glucose promotes cognitive engagement and protects positive affect in older adults” by Mantantzis, Konstantinos; Maylor, Elizabeth A.; and Schlaghecken, Friederike in Psychology and Aging. Published July 12 2018.
doi:10.1037/pag0000270

Abstract

Gain without pain: Glucose promotes cognitive engagement and protects positive affect in older adults

When faced with a cognitively demanding task, older adults tend to disengage and withdraw effort. At the same time, their usual processing preference for positive information disappears. Providing glucose as an energy resource is known to improve cognitive performance and reinstate older adults’ positivity preference. Here, we examined whether glucose can help older adults to exert more effort under high difficulty conditions, and if so, whether such increase is accompanied by a change in positive affect. Fifty-three young and 58 older adults consumed a glucose or a placebo drink and completed a memory-search task at three levels of difficulty. Cognitive engagement was measured through changes in heart rate (HR) and self-reported effort. After each memory-search block, participants completed an implicit emotion-assessment task. In both age groups, glucose produced increased HR (indicating higher task engagement) relative to placebo. In older but not in young adults, glucose also improved cognitive performance and increased positive affect. Subjective effort, in contrast, did not differ between the older-glucose and older-placebo groups. These results suggest that in older adults, glucose improves cognitive performance by promoting higher cognitive engagement while mitigating the subjective costs of effortful exertion.

A woman’s history of pregnancy may affect her risk of Alzheimer’s disease decades later, according to a study published in the July 18, 2018, online issue of Neurology. The study found that women who give birth to five or more children may be more likely to develop Alzheimer’s disease than women who have fewer births. The study also showed that women who have had an incomplete pregnancy, whether through miscarriage or abortion, are less likely to develop Alzheimer’s disease in the future than women who have never had an incomplete pregnancy.

“Estrogen levels double by the eighth week of pregnancy before climbing to up to 40 times the normal peak level,” said study author Ki Woong Kim, MD, PhD, of Seoul National University in Seoul, South Korea. “If these results are confirmed in other populations, it is possible that these findings could lead to the development of hormone-based preventive strategies for Alzheimer’s disease based on the hormonal changes in the first trimester of pregnancy.”

For the study, researchers combined the data from two, independent population-based studies from Korea and Greece, with a total of 3,549 women. Women who were currently taking hormone replacement therapy and those who had a hysterectomy or surgery to remove the ovaries were not included in the study.

The women, who were an average age of about 71 at the start of the study, provided information on their reproductive history. They took the diagnostic examination after an average of 46 years from their first childbirth. During that time, the participants took tests of their memory and thinking skills to see whether they had developed Alzheimer’s disease or its precursor, mild cognitive impairment. A total of 118 women developed Alzheimer’s disease and 896 women developed mild cognitive impairment.

Women who had given birth to five or more children were 70 percent more likely to develop Alzheimer’s disease than women who gave birth to fewer children. Of the 716 women with five or more children, 59 developed Alzheimer’s disease, compared to 53 of the 2,751 women with fewer children. The results stayed the same after researchers adjusted for other factors, such as other medical conditions, use of hormone replacement therapy and breastfeeding.

Women who had experienced an incomplete pregnancy were about half as likely to develop Alzheimer’s disease as women who had never had an incomplete pregnancy. Of the 2,375 women who had an incomplete pregnancy, 47 developed Alzheimer’s disease, compared to 71 of the 1,174 women who never had an incomplete pregnancy.

On the tests of memory and thinking skills, women who had five or more children had lower scores than women who had fewer children. On a test where the maximum score is 30 points and scores of 24 or more indicate normal thinking skills and scores of 19 to 23 indicate mild cognitive problems, the women with five or more children had average scores of about 22 points, compared to almost 26 points for the women with fewer than five children.

Women who had one or more incomplete pregnancies had higher test scores than women with no incomplete pregnancies, regardless of how many children they had. For example, among women with five or more children, those with no incomplete pregnancies had average scores of about 22, compared to scores of more than 23 points for those with one or more incomplete pregnancy.

“It’s possible that the modestly raised levels of estrogen in the first trimester of pregnancy are within the optimal range for protecting thinking skills,” Kim said.

A limitation of the study is that incomplete pregnancies may be been underestimated either because abortions were not reported or because women may not have realized that they had miscarriages. Another limitation is that the researchers did not collect information on the timing and cause of incomplete pregnancies.

Funding: The study was funded by the Korean Ministry of Health and Welfare, Alzheimer’s Association, European Social Fund, Greek Ministry for Health and Social Solidarity, and National Health and Medical Research Council of Australia.

Source: AAN
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Abstract for “Differential effects of completed and incomplete pregnancies on the risk of Alzheimer disease” by Hyesue Jang, Jong Bin Bae, Efthimios Dardiotis, Nikolaos Scarmeas, Perminder S. Sachdev, Darren M. Lipnicki, Ji Won Han, Tae Hui Kim, Kyung Phil Kwak, Bong Jo Kim, Shin Gyeom Kim, Jeong Lan Kim, Seok Woo Moon, Joon Hyuk Park, Seung-Ho Ryu, Jong Chul Youn, Dong Young Lee, Dong Woo Lee, Seok Bum Lee, Jung Jae Lee, Jin Hyeong Jhoo, Mary Yannakoulia, Mary H. Kosmidis, Giorgos M. Hadjigeorgiou, Paraskevi Sakka, Ki Woong Kim in Neurology. Published July 18 2018.
doi:10.1212/WNL.0000000000006000

Abstract

Differential effects of completed and incomplete pregnancies on the risk of Alzheimer disease

Objective
To investigate the effects of completed pregnancy with childbirth and incomplete pregnancy without childbirth on the late-life cognition and the risk of Alzheimer disease (AD) in women.

Methods
Using the pooled data of 3,549 women provided by 2 population-based cohort studies, we conducted logistic regression analyses to examine retrospectively the associations of completed and incomplete pregnancy with the risks of mild cognitive impairment and AD. For women without dementia, we also conducted analyses of covariance to examine the associations of completed and incomplete pregnancy with Mini-Mental State Examination (MMSE) score.

Results
Grand multiparous women who experienced ≥5 completed pregnancies showed an ≈1.7-fold higher risk of AD than those who experienced 1 to 4 completed pregnancies (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.04–2.72), while those who had incomplete pregnancies showed half the level of AD risk compared with those who never experienced an incomplete pregnancy (OR 0.43, 95% CI 0.24–0.76 for 1 incomplete pregnancy; OR 0.56, 95% CI 0.34–0.92 for ≥2 incomplete pregnancies). In women without dementia, the grand multiparous had worse MMSE scores than those with 1 to 4 completed pregnancies (p < 0.001), while those who experienced ≥1 incomplete pregnancies had better MMSE scores than those who never experienced an incomplete pregnancy (p = 0.008).

Conclusions
Grand multiparity was associated with high risk of AD, while incomplete pregnancy was associated with low risk of AD in late life.

Summary: A new study reports when certain brain areas react more strongly to food rewards than financial rewards, children are more likely to overeat, even if they are not hungry or overweight.

Source: Penn State.

The reason why some people find it so hard to resist finishing an entire bag of chips or bowl of candy may lie with how their brain responds to food rewards, leaving them more vulnerable to overeating.

In a study with children, researchers found that when certain regions of the brain reacted more strongly to being rewarded with food than being rewarded with money, those children were more likely to overeat, even when the child wasn’t hungry and regardless of if they were overweight or not.

Shana Adise, a postdoctoral fellow at the University of Vermont who led the study while earning her doctorate at Penn State, said the results give insight into why some people may be more prone to overeating than others. The findings may also give clues on how to help prevent obesity at a younger age.

“If we can learn more about how the brain responds to food and how that relates to what you eat, maybe we can learn how to change those responses and behavior,” Adise said. “This also makes children an interesting population to work with, because if we can stop overeating and obesity at an earlier age, that could be really beneficial.”

Previous research on how the brain’s response to food can contribute to overeating has been mixed. Some studies have linked overeating with brains that are more sensitive to food rewards, while others have found that being less sensitive to receiving food rewards makes you more likely to overeat.

Additionally, other studies have shown that people who are willing to work harder for food than other types of rewards, like money, are more likely to overeat and gain weight over time. But the current study is the first to show that children who have greater brain responses to food compared to money rewards are more likely to overeat when appealing foods are available.

“We know very little about the mechanisms that contribute to overeating,” Adise said. “The scientific community has developed theories that may explain overeating, but whether or not they actually relate to food intake hadn’t yet been evaluated. So we wanted to go into the lab and test whether a greater brain response to anticipating and winning food, compared to money, was related to overeating.”

For the study, 59 children between the ages of 7 and 11 years old made four visits to the Penn State’s Children’s Eating Behavior Laboratory.

During the first three visits, the children were given meals designed to measure how they eat in a variety of different situations, such as a typical meal when they’re hungry versus snacks when they’re not hungry. How much the children ate at each meal was determined by weighing the plates before and after the meals.

On their fourth visit, the children had fMRI scans as they played several rounds of a game in which they guessed if a computer-generated number would be higher or lower than five. They were then told that if they were right, they would win either money, candy or a book, before it was revealed if they were correct or not.

The researchers found that when various regions of the brain reacted more to anticipating or winning food compared to money, those children were more likely to overeat.

“We also found that the brain’s response to food compared to money was related to overeating regardless of how much the child weighed,” Adise said. “Specifically, we saw that increased brain responses in areas of the brain related to cognitive control and self control when the children received food compared to money were associated with overeating.”

Adise added that this is important because it suggests there may be a way to identify brain responses that can predict the development of obesity in the future.

Kathleen Keller, associate professor of nutritional sciences, Penn State, said the study — recently published in the journal Appetite — backs up the theory that an increased brain response in regions of the brain related to rewards is associated with eating more food in a variety of situations.

“We predicted that kids who had an increased response to food relative to money would be the ones to overeat, and that’s what we ended up seeing,” Keller said. “We specifically wanted to look at kids whose brains responded to one type of a reward over another. So it wasn’t that they’re overly sensitive to all rewards, but that they’re highly sensitive to food rewards.”

Keller said the findings give insight into how the brain influences eating, which is important because it could help identify children who are at risk for obesity or other poor eating habits before those habits actually develop.

“Until we know the root cause of overeating and other food-related behaviors, it’s hard to give good advice on fixing those behaviors,” Keller said. “Once patterns take over and you overeat for a long time, it becomes more difficult to break those habits. Ideally, we’d like to prevent them from becoming habits in the first place.”

Charles F. Geier, associate professor of human development and family studies, Penn State; Nicole J. Roberts, doctoral candidate in human development and family studies, Penn State; and Corey N. White, Missouri Western State University, also participated in this research.

Funding: This work was supported by a Childhood Obesity Prevention Training grant and Penn State’s Social, Life, and Engineering Sciences Imaging Center.

Source: Katie Bohn – Penn State
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Abstract for “Is brain response to food rewards related to overeating? A test of the reward surfeit model of overeating in children” by Shana Adise, Charles F. Geier, Nicole J. Roberts, Corey N. White, Kathleen L. Keller in Appetite. Published June 8 2018.
doi:10.1016/j.appet.2018.06.014

Abstract

Is brain response to food rewards related to overeating? A test of the reward surfeit model of overeating in children

The reward surfeit model of overeating suggests that heightened brain response to rewards contributes to overeating and subsequent weight gain. However, previous studies have not tested whether brain response to reward is associated with food intake, particularly during childhood, a period of dynamic development in reward and inhibitory control neurocircuitry. We conducted functional magnetic resonance imaging (fMRI) with 7–11-year-old children (n = 59; healthy weight, n = 31; overweight, n = 28; 54% female) while they played a modified card-guessing paradigm to examine blood-oxygen-level-dependent (BOLD) response to anticipating and winning rewards (food, money, neutral). Food intake was assessed at three separate meals that measured different facets of eating behavior: 1) typical consumption (baseline), 2) overindulgence (palatable buffet), and 3) eating in the absence of hunger (EAH). A priori regions of interest included regions implicated in both reward processing and inhibitory control. Multiple stepwise regressions were conducted to examine the relationship between intake and BOLD response to rewards. Corrected results showed that a greater BOLD response in the medial prefrontal cortex for anticipating food compared to money positively correlated with how much children ate at the baseline and palatable buffet meals. BOLD response in the dorsolateral prefrontal cortex for winning food compared to money was positively correlated with intake at the palatable buffet meal and EAH. All aforementioned relationships were independent of child weight status. Findings support the reward surfeit model by showing that increased brain response to food compared to money rewards positively correlates with laboratory measures of food intake in children.

Source: Kobe University.

A group of Japanese researchers has discovered that neural inflammation caused by our innate immune system plays an unexpectedly important role in stress-induced depression. This insight could potentially lead to the development of new antidepressants targeting innate immune molecules. The findings were published in the online edition of Neuron.

The joint study was led by Professor Tomoyuki Furuyashiki and Assistant Professor Shiho Kitaoka (Kobe University Graduate School of Medicine) in collaboration with Project Professor Shuh Narumiya (Kyoto University Graduate School of Medicine).

Previous research had already hinted at the link between inflammation and depression: increased levels of inflammation-related cytokines in the blood of patients suffering from depression, activation of microglia (inflammation-related cells in the brain) in depressive patients, and a high percentage of depression outbreaks in patients suffering from chronic inflammatory disease. However, the exact relationship between depression and inflammation still contains many unknowns.

Psychological stress caused by social and environmental factors can trigger a variety of changes in both mind and body. Moderate levels of stress will provoke a defensive response, while extreme stress can lower our cognitive functions, cause depression and elevated anxiety, and is a risk factor for mental illnesses. The research team focused on repeated social defeat stress (a type of environmental stress) with the aim of clarifying the mechanism that causes an emotional response to repeated stress.

First, they looked at changes of gene expression in the brain caused by repeated social defeat stress and found that repeated stress increased a putative ligand for the innate immune receptors TLR2 and TLR4 (TLR2/4) in the brain. Their next step was to investigate the role of TLR2/4 in repeated stress using a mouse with the TLR2/4 genes deleted. They found that TLR2/4-deficient mice did not show social avoidance or extreme anxiety when exposed to repeated stress. Repeated stress usually triggers microglial activation in specific areas of the brain such as the medial prefrontal cortex, causing impaired response and atrophy of neurons, but these responses were not present in the TLR2/4-deficient mice.

The research team then developed a method to selectively block the expression of TLR2/4 in the microglia of specific areas of the brain. By blocking the expression of TLR2/4 in the microglia of the medial prefrontal cortex, they managed to suppress depressive behavior in response to repeated social defeat stress. They found that repeated stress induced the expression of inflammation-related cytokines IL-1α and TNFα in the microglia of the medial prefrontal cortex via TLR2/4. The depressive behavior was suppressed by treating the medial prefrontal cortex with neutralizing antibodies for the inflammation-related cytokines.

These results show that repeated social defeat stress activates microglia in the medial prefrontal cortex via the innate immune receptors TLR2/4. This triggers the expression of inflammation-related cytokines IL-1α and TNFα, leading to the atrophy and impaired response of neurons in the medial prefrontal cortex, and causing depressive behavior.

Professor Furuyashiki says: “These findings demonstrate the importance of neural inflammation caused by the innate immune system for stress-induced depression. This could lead to the development of new antidepressant medication targeting innate immune molecules”.

Funding: Japan Agency for Medical Research and Development, Japan Science and Technology Agency, Japan Society for the Promotion of Science, Ministry of Education Culture Sports Science and Technology in Japan, Uehara Memorial Foundation, Sumitomo Foundation funded this study.

Source: Eleanor Wyllie – Kobe University
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is credited to Kobe University.
Original Research: Abstract for “The Innate Immune Receptors TLR2/4 Mediate Repeated Social Defeat Stress-Induced Social Avoidance through Prefrontal Microglial Activation” by Xiang Nie, Shiho Kitaoka, Kohei Tanaka, Eri Segi-Nishida, Yuki Imoto, Atsubumi Ogawa, Fumitake Nakano, Ayaka Tomohiro, Kazuki Nakayama, Masayuki Taniguchi, Yuko Mimori-Kiyosue, Akira Kakizuka, Shuh Narumiya’Correspondence information about the author Shuh NarumiyaEmail the author Shuh Narumiya, Tomoyuki Furuyashiki in Neuron. Published July 19 2018.
doi:10.1016/j.neuron.2018.06.035

Abstract

The Innate Immune Receptors TLR2/4 Mediate Repeated Social Defeat Stress-Induced Social Avoidance through Prefrontal Microglial Activation

Highlights
•Repeated stress activates mPFC microglia through innate immune receptors TLR2/4
•Activated microglia induce response attenuation and atrophy of mPFC neurons
•Activated microglia underlie repeated stress-induced social avoidance
•TLR2/4 induce IL-1α and TNF-α in mPFC microglia, leading to social avoidance

Summary
Repeated environmental stress has been proposed to induce neural inflammation together with depression and anxiety. Innate immune receptors, such as Toll-like receptors (TLRs), are activated by exogenous or endogenous ligands to evoke inflammation. Here we show that the loss of TLR2 and TLR4 (TLR2/4) abolished repeated social defeat stress (R-SDS)-induced social avoidance and anxiety in mice. TLR2/4 deficiency mitigated R-SDS-induced neuronal response attenuation, dendritic atrophy, and microglial activation in the medial prefrontal cortex (mPFC). Furthermore, mPFC microglia-specific TLR2/4 knockdown blocked social avoidance. Transcriptome analyses revealed that R-SDS induced IL-1α and TNF-α in mPFC microglia in a TLR2/4-dependent manner, and antibody blockade of these cytokines in the mPFC suppressed R-SDS-induced social avoidance. These results identify TLR2/4 as crucial mediators of R-SDS-induced microglial activation in the mPFC, which leads to neuronal and behavioral changes through inflammation-related cytokines, highlighting unexpected pivotal roles of innate immunity in the mPFC in repeated environmental stress-induced behavioral changes.

Summary: Researchers report rats exposed to phthalates, both while in the womb and through lactation, had fewer neurons and synapses than peers who were not exposed to the plasticizing chemicals. Additionally, the phthalate exposed rats showed deficits in cognitive flexibility.

Source: University of Illinois.

Male and female rats exposed in the womb and during lactation to plasticizing chemicals known as phthalates had significantly fewer neurons and synapses than those that were not exposed, researchers report in a new study. The phthalate-exposed rats had reductions in the size of their medial prefrontal cortex, a brain region that regulates behavior, and showed deficits in cognitive flexibility.

The variety of phthalates and quantities used in the study were environmentally relevant to human exposures, said University of Illinois psychology professor Janice Juraska, who led the research.

“Phthalates are used as plasticizers in a variety of consumer goods, including plastics, personal care products, fragrances, pharmaceuticals, clothing and building materials,” she said. “Contact with these products can lead to exposure through the skin, digestion or lungs.”

Research has shown that phthalates readily cross the placenta to expose a developing fetus, and that they can be delivered to offspring via lactation, Juraska said. Because these chemicals can disrupt normal hormone signaling, their presence in infants and children is of special concern. The developing brain, in particular, is susceptible to hormone disruptions. Several studies in humans suggest that prenatal phthalate exposure may negatively affect children’s behavior, their ability to regulate their own actions and the incidence of neuropsychiatric disorders, she said.

The pregnant rats in the study were each assigned to one of three groups – two of which were exposed to differing concentrations of phthalates during pregnancy and lactation, and one, a control group, that was not exposed at all. The researchers tested how well the offspring learned to use visual and textural cues to navigate a maze, and examined the relative development of their brains once they reached adulthood.

“We found that there was an appreciable reduction in the number of neurons, the number of synapses and the size of the medial prefrontal cortex in the phthalate-exposed rats,” Juraska said. “They also showed a deficit in what we call cognitive flexibility. They made significantly more errors when navigating the mazes than rats that had not been exposed.”

The negative effects of perinatal exposure to phthalates were seen at both doses of the phthalate mixture, the researchers report, which were “presumably within the range of the estimated daily intakes of humans.”

Funding: Juraska is an affiliate of the Beckman Institute for Advanced Science and Technology at Illinois. The National Institute of Environmental Health Sciences and the U.S. Environmental Protection Agency supported this research.

Source: Diana Yates – University of Illinois
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Abstract for “Perinatal exposure to an environmentally relevant mixture of phthalates results in a lower number of neurons and synapses in the medial prefrontal cortex and decreased cognitive flexibility in adult male and female rats” by Daniel G. Kougias, Elli P. Sellinger, Jari Willing and Janice M. Juraska in Journal of Neuroscience. Published July 16 2018.
doi:10.1523/JNEUROSCI.0607-18.2018

Abstract

Perinatal exposure to an environmentally relevant mixture of phthalates results in a lower number of neurons and synapses in the medial prefrontal cortex and decreased cognitive flexibility in adult male and female rats

The growth and organization of the developing brain is known to be influenced by hormones, but little is known about whether disruption of hormones affects cortical regions, like the medial prefrontal cortex (mPFC). This region is particularly important given its involvement in executive functions and implication in the pathology of many neuropsychiatric disorders. Here, we examine the long-term effects of perinatal exposure to endocrine-disrupting compounds, the phthalates, on the mPFC and associated behavior. This investigation is pertinent as humans are ubiquitously exposed to phthalates through a variety of consumer products and phthalates can readily cross the placenta and be delivered to offspring via lactation. Pregnant dams orally consumed an environmentally relevant mixture of phthalates at 0, 200, or 1000 μg/kg/day through pregnancy and for 10 days while lactating. As adults, offspring were tested in an attentional set-shifting task, which assesses cognitive flexibility. Brains were also examined in adulthood for stereological quantification of the number of neurons, glia, and synapses within the mPFC. We found that, independent of sex, perinatal phthalate exposure at either dose resulted in a reduction in neuron number, synapse number, and size of the mPFC and a deficit in cognitive flexibility. Interestingly, the number of synapses was correlated with cognitive flexibility, such that rats with fewer synapses were less cognitively flexible than those with more synapses. These results demonstrate that perinatal phthalate exposure can have long-term effects on the cortex and behavior of both male and female rats.

SIGNIFICANCE STATEMENT

Humans globally are exposed on a daily basis to a variety of phthalates, which are endocrine-disrupting chemicals. The effects of phthalate exposure on the developing brain, especially on cognitively relevant regions like the medial prefrontal cortex (mPFC), is not known. Here, we use a rat model of human prenatal exposure to an environmentally relevant mixture of phthalates and find there is an appreciable reduction in neuron number, synapse number, and size of the mPFC and a deficit in cognitive flexibility. These results may have serious implications for humans given the mPFC is involved in executive functions and is implicated in the pathology of many neuropsychiatric disorders.