How brain circuits govern hunger and cravings

The urge to satisfy hunger is a primal one, but — as any dieter knows — choices about when and what to eat can be influenced by cues in the environment, not just how long it’s been since breakfast. The fact that food-associated visual cues in television commercials and on highway signs can contribute to overeating is well-documented. But how exactly do these external signals trigger cravings and influence behavior?

By developing a new approach to imaging and manipulating particular groups of neurons in the mouse brain, scientists at Beth Israel Deaconess Medical Center (BIDMC) have identified a pathway by which neurons that drive hunger influence distant neurons involved in the decision of whether or not to react to food-related cues. Their findings could open the door to targeted therapies that dampen food cue-evoked cravings in people with obesity. The research was published online today in the journal Nature.

“The main question we were asking is: how do evolutionarily ancient hunger-promoting neurons at the base of the brain, in the hypothalamus, influence ‘cognitive’ brain areas to help us find and eat calorie-rich foods in a complex and changing world?” said co-corresponding author Mark Andermann, PhD, an Assistant Professor of Medicine in the Division of Endocrinology, Diabetes and Metabolism at BIDMC and Assistant Professor at Harvard Medical School (HMS).

“To put it simply, when you’re hungry, the picture of a cheeseburger may be extremely appealing and effective in influencing your behavior,” explained lead author Yoav Livneh, PhD, postdoctoral fellow at BIDMC. “But if your belly is full after eating a big meal, the same cheeseburger picture will be unappealing. We think that the pathway we discovered from hunger-promoting neurons to a region of the brain called the insular cortex plays an important role here.”

Brain imaging data in humans support the notion that the insular cortex is involved in deciding if a source of food is worth pursuing. In healthy humans, the insular cortex increases its activity in response to food cues during hunger but not following a meal. Studies suggest that this process often goes awry in patients with obesity or other eating disorders that exhibit excessive cravings. Those findings indicate that specific changes in brain activity, including increased sensitivity to food cues, may underlie these disorders — rather than a ‘lack of willpower’.

In their study, Livneh, Andermann and co-corresponding author Bradford B. Lowell, MD, PhD, Professor of Medicine in the Division of Endocrinology, Diabetes and Metabolism at BIDMC and Professor of Medicine at HMS, and colleagues focused on the insular cortex, using a mouse model. Because the mouse insular cortex is located at the side of the brain in a hard-to-reach place, Andermann, Lowell, Livneh and colleagues pioneered the use of a tiny periscope that allowed them to see neurons in this previously unobservable part of the brain. The tool allowed the researchers to monitor and track individual neurons in awake mice as they responded to food cues in both sated and hungry physiological states.

Their experiments demonstrated that visual cues associated with food would specifically activate a certain group of neurons in the insular cortex of hungry mice, and that these neurons were necessary for mice to respond behaviorally to food cues. After mice had eaten until they were full, this brain response to food cues in the insular cortex was no longer present. While the mice were still sated, the researchers used genetic techniques to artificially create hunger by ‘turning on’ hunger-promoting neurons in the hypothalamus. These neurons express the gene for Agouti-related protein (AgRP) and were previously shown to restore simple feeding behaviors. By activating these AgRP neurons, Livneh and colleagues caused sated mice to once again react to visual stimuli and seek more food, and it also restored the pattern of food cue visual responses across neurons in insular cortex to that previously seen in hungry mice.

“These AgRP neurons cause hunger — they are the quintessential hunger neuron,” explained Lowell. “It’s a major advance to learn that we can artificially turn them on and cause full mice to work to get food and to eat as if they hadn’t eaten in a long time. These neurons seem capable of causing a diverse set of behaviors associated with hunger and eating.”

Based on their research, it may also be possible to dial down the specific pathway from AgRP neurons to the insular cortex and reduce over-attention to food cues in the environment, ideally without impacting deliberate eating at mealtimes. This hypothesis requires further investigation, the researchers stress, but has exciting implications for the treatment of human obesity and other eating disorders.

With their unprecedented view into the insular cortex, Andermann and Lowell’s team created a road map of the brain circuitry by which hunger-related AgRP neurons ultimately influence insular cortex. Using powerful genetic and optical methods to switch individual cells on and off at will, the team could observe the effects both on downstream neurons and on behavior. The circuitry they revealed includes the amygdala, thought to update the value of food cues, and the paraventricular thalamus, which is also important for motivated behaviors. The researchers suggest the pathway may bias decision-making by increasing the pros and decreasing the cons of seeking out and eating a given food.

“We’re still trying to understand how this process works,” said Lowell. “Huge questions remain, but they are now addressable thanks to these new imaging methods.”

 

Surprising new link between inflammation and mental illness

Up to 75 percent of patients with systemic lupus erythematosus — an incurable autoimmune disease commonly known as lupus — experience neuropsychiatric symptoms. But so far, our understanding of the mechanisms underlying lupus’ effects on the brain has remained murky. Now, new research from Boston Children’s Hospital has shed light on the mystery and points to a potential new drug for protecting the brain from the neuropsychiatric effects of lupus and other central nervous system (CNS) diseases. The team has published its surprising findings in Nature.

“In general, lupus patients commonly have a broad range of neuropsychiatric symptoms, including anxiety, depression, headaches, seizures, even psychosis,” says Allison Bialas, PhD, first author on the study and a research fellow working in the lab of Michael Carroll, PhD, senior author on the study, who are part of the Boston Children’s Program in Cellular and Molecular Medicine. “But their cause has not been clear — for a long time it wasn’t even appreciated that these were symptoms of the disease.

Collectively, lupus’ neuropsychiatric symptoms are known as central nervous system (CNS) lupus. Carroll’s team wondered if changes in the immune system in lupus patients were directly causing these symptoms from a pathological standpoint.

“How does chronic inflammation affect the brain?”

Lupus, which affects at least 1.5 million Americans, causes the immune systems to attack the body’s tissues and organs. This causes the body’s white blood cells to release type 1 interferon-alpha, a small cytokine protein that acts as a systemic alarm, triggering a cascade of additional immune activity as it binds with receptors in different tissues.

Until now, however, these circulating cytokines were not thought to be able to cross the blood brain barrier, the highly-selective membrane that controls the transfer of materials between circulating blood and the central nervous system (CNS) fluids.

“There had not been any indication that type 1 interferon could get into the brain and set off immune responses there,” says Carroll, who is also professor of pediatrics at Harvard Medical School.

So, working with a mouse model of lupus, it was quite unexpected when Carroll’s team discovered that enough interferon-alpha did indeed appear to permeate the blood brain barrier to cause changes in the brain. Once across the barrier, it launched microglia — the immune defense cells of the CNS — into attack mode on the brain’s neuronal synapses. This caused synapses to be lost in the frontal cortex.

“We’ve found a mechanism that directly links inflammation to mental illness,” says Carroll. “This discovery has huge implications for a range of central nervous system diseases.”

Blocking inflammation’s effects on the brain

The team decided to see if they could reduce synapse loss by administering a drug that blocks interferon-alpha’s receptor, called an anti-IFNAR.

Remarkably, they found that anti-IFNAR did seem to have neuro-protective effects in mice with lupus, preventing synapse loss when compared with mice who were not given the drug. What’s more, they noticed that mice treated with anti-IFNAR had a reduction in behavioral signs associated with mental illnesses such as anxiety and cognitive defects.

Although further study is needed to determine exactly how interferon-alpha is crossing the blood brain barrier, the team’s findings establish a basis for future clinical trials to investigate the effects of anti-IFNAR drugs on CNS lupus and other CNS diseases. One such anti-IFNAR, anifrolumab, is currently being evaluated in a phase 3 human clinical trial for treating other aspects of lupus.

“We’ve seen microglia dysfunction in other diseases like schizophrenia, and so now this allows us to connect lupus to other CNS diseases,” says Bialas. “CNS lupus is not just an undefined cluster of neuropsychiatric symptoms, it’s a real disease of the brain — and it’s something that we can potentially treat.”

The implications go beyond lupus because inflammation underpins so many diseases and conditions, ranging from Alzheimer’s to viral infection to chronic stress.

“Are we all losing synapses, to some varying degree?” Carroll suggests. His team plans to find out.

 

Dressmakers found to have needle-sharp 3-D vision

Haute couture can be credited for enhancing more than catwalks and red carpets. New research from the University of California, Berkeley suggests that the 3D or “stereoscopic” vision of dressmakers is as sharp as their needles.

Stereoscopic vision is the brain’s ability to decode the flat 2D optical information received by both eyes to give us the depth of perception needed to thread a needle, catch a ball, park a car and generally navigate a 3D world.

Using computerized perceptual tasks, researchers from UC Berkeley and the University of Geneva, Switzerland, tested the stereoscopic vision of dressmakers and other professionals, and found dressmakers to be the most eagle-eyed.

The results, published in the June 13 issue of the journal Scientific Reports, show dressmakers to be 80 percent more accurate than non-dressmakers at calculating the distance between themselves and the objects they were looking at, and 43 percent better at estimating the distance between objects.

“We found dressmakers have superior stereovision, perhaps because of the direct feedback involved with fine needlework,” said study lead author Adrien Chopin, a postdoctoral researcher in visual neuroscience at UC Berkeley.

What researchers are still determining is whether dressmaking sharpens stereoscopic vision, or whether dressmakers are drawn to the trade because of their visual stereo-acuity, Chopin said.

To experience what it means to have stereoscopic vision, focus on a visual target. Now blink one eye while still staring at your target. Then blink the other eye. The background should appear to shift position. With stereoscopic vision, the brain’s visual cortex merges the 2D viewpoints of each eye into one 3D image.

It has generally been assumed that surgeons, dentists and other medical professionals who perform precise manual procedures would have superior stereovision. But previous studies have shown this not to be the case.

That spurred Chopin to investigate which professions would produce or attract people with superior stereovision, and led him to dressmakers.

A better understanding of dressmakers’ stereoscopic superpowers will inform ongoing efforts to train people with visual impairments such as amblyopia or “lazy eye” to strengthen their stereoscopic vision, Chopin said.

In addition to helping people with sight disorders, improved stereoscopic vision may be key to the success of military fighters, athletes and other occupations that require keen hand-eye coordination. An estimated 10 percent of people suffer from some form of stereoscopic impairment, and 5 percent suffer from full stereo blindness, Chopin said.

For example, the 17th-century Dutch painter Rembrandt, whose self-portraits occasionally showed him with one lazy eye, is thought to have suffered from stereo blindness, rendering him with flat vision. Some vision scientists have posited that painters tend to have poorer stereovision, which gives them an advantage working in 2D.

For the study, participants viewed objects on a computer screen through a stereoscope and judged the distances between objects, and between themselves and the objects. Researchers recorded their visual precision and found that, overall, dressmakers performed markedly better than their non-dressmaker counterparts in visual acuity.

Story Source:

Materials provided by University of California – Berkeley. Original written by Yasmin Anwar. Note: Content may be edited for style and length.

 

People who are ‘phone snubbed’ by others often turn to their own phones, social media for acceptance, study finds

People who are phone snubbed — or “phubbed” — by others are, themselves, often turning to their smartphones and social media to find acceptance, according to new research from Baylor University’s Hankamer School of Business.

Building on their earlier study that phubbing can damage relationships and lead to depression, researchers Meredith David, Ph.D., assistant professor of marketing, and James A. Roberts, Ph.D., The Ben H. Williams Professor of Marketing, have found that the circle nearly completes itself as the offended parties frequently jump online to find affirmation in the likes and shares and positive comments of social media.

Their study, “Phubbed and Alone: Phone Snubbing, Social Exclusion, and Attachment to Social Media,” is published in the Journal of the Association for Consumer Research. The research investigates the relationship between phubbing, social media attachment, depression, anxiety and stress.

“When an individual is phubbed, he/she feels socially excluded which leads to an increased need for attention. Instead of turning to face-to-face interaction to restore a sense of inclusion, study participants turned to social media to regain a sense of belonging,” said David, lead author of the study. “Being phubbed was also found to undermine an individual’s psychological well-being. Phubbed individuals reported higher levels of stress and depression.”

“We’re looking online for what we’re not getting offline,” Roberts said. “It’s a vicious cycle.”

As part of their research, David and Roberts surveyed more than 330 people across two studies. They found:

  • Nearly half of those who were phubbed reported spending more than 1.5 hours on their phone each day. In addition, one-quarter of those phubbed reported spending more than 90 minutes per day on social media sites.
  • More than one-third of phubbed individuals indicated that they turn to social media to interact with new people.
  • More than half of individuals who said they were phubbed indicated that social media enhances their life and makes their life better overall. The majority of these individuals reported that people’s comments on their social media posts makes them feel affirmed and more accepted.

“Although the stated purpose of technology like smartphones is to help us connect with others, in this particular instance, it does not,” David said. “Ironically, the very technology that was designed to bring humans closer together, has isolated us from these very same people.”

Roberts, who wrote the book “Too Much of a Good Thing: Are You Addicted to Your Smartphone?” said this current research and the trends it identifies are troubling.

“Our inability to separate from technology is devastating to our well-being,” he said. “Even if it’s not an addiction, it’s a deeply engrained habit.”

To counter the negative effects of smartphone use, the researchers advise consumers to establish “smartphone-free” zones and times; establish social contracts (and penalties) regarding phone use with friends, family and coworkers; and downloading apps that track, monitor and control smartphone use.

“All this research into phubbing would be for naught, or only an interesting story, if not for the revelation that this type of behavior can drive others’ use of social media in an attempt to regain inclusion,” the researchers wrote. “Additionally, such behavior can also impact the well-being of affected individuals.”

Story Source:

Materials provided by Baylor University. Note: Content may be edited for style and length.

Making art activates brain’s reward pathway

Your brain’s reward pathways become active during art-making activities like doodling, according to a new Drexel University study.

Girija Kaimal, EdD, assistant professor in the College of Nursing and Health Professions, led a team that used fNIRS (functional near-infrared spectroscopy) technology to measure blood flow in the areas of the brain related to rewards while study participants completed a variety of art-making projects.

“This shows that there might be inherent pleasure in doing art activities independent of the end results. Sometimes, we tend to be very critical of what we do because we have internalized, societal judgements of what is good or bad art and, therefore, who is skilled and who is not,” said Kaimal of the study that was published The Arts in Psychotherapy. “We might be reducing or neglecting a simple potential source of rewards perceived by the brain. And this biologocial proof could potentially challenge some of our assumptions about ourselves.”

For the study, co-authored by Drexel faculty including Jennifer Nasser, PhD, and Hasan Ayaz, PhD, 26 participants wore fNIRS headbands while they completed three different art activities (each with rest periods between). For three minutes each, the participants colored in a mandala, doodled within or around a circle marked on a paper, and had a free-drawing session.

During all three activities, there was a measured increase in bloodflow in the brain’s prefrontal cortex, compared to rest periods where bloodflow decreased to normal rates.

The prefrontal cortex is related to regulating our thoughts, feelings and actions. It is also related to emotional and motivational systems and part of the wiring for our brain’s reward circuit. So seeing increased bloodflow in these areas likely means a person is experiencing feels related to being rewarded.

There were some distinctions between the activities in the data collected.

Doodling in or around the circle had the highest average measured bloodflow increase in the reward pathway compared to free-drawing (the next highest) and coloring. However, the difference between each form of art-making was not statistically significant, according to analysis.

“There were some emergent differences but we did not have a large-enough sample in this initial study to draw any definitive conclusions,” Kaimal said.

It was noted and tracked which participants in the study considered themselves artists so that their results could be compared to non-artists. In that way, Kaimal and her team hoped to understand whether past experience played a factor in triggering feelings of reward.

Doodling seemed to initiate the most brain activity in artists, but free-drawing was observed to be about the same for artists and non-artists. Interestingly, the set coloring activity actually resulted in negative brain activity in artists.

“I think artists might have felt very constrained by the pre-drawn shapes and the limited choice of media,” Kaimal explained. “They might also have felt some frustration that they could not complete the image in the short time.”

Again, however, these results regarding artists versus non-artists proved statistically insignificant, which might actually track with Kaimal’s previous research that found experience-level did not have a bearing on the stress-reduction benefits people had while making art.

Overall, though, the finding that any form of art-making resulted in the significant activation of feelings of reward are compelling, especially for art therapists who see art as a valuable tool for mental health.

In fact, in surveys administered to the participants after the activities were complete, respondents indicated that they felt more like they had “good ideas” and could “solve problems” than before the activities. Participants even said they felt the three-minute time spans for art-making weren’t long enough.

“There are several implications of this study’s findings,” Kaimal said. “They indicate an inherent potential for evoking positive emotions through art-making — and doodling especially. Doodling is something we all have experience with and might re-imagine as a democratizing, skill independent, judgment-free pleasurable activity.”

Additionally, Kaimal felt that the findings of increased self-opinion were intriguing.

“There might be inherent aspects to visual self-expression that evoke both pleasure and a sense of creative agency in ourselves,” she said.

Female and male mice suffer, recover from TBI differently

Male mice have much greater brain distress in the week following a traumatic brain injury (TBI) than female mice, including skyrocketing inflammation and nerve cell death, say researchers at Georgetown University Medical Center.

The study, published in GLIA, is the first to specifically examine how sex alters the time-course of inflammation in the brain after TBI, and their findings suggest that sex is an important factor to consider when designing and testing new drugs to treat TBI.

Previous research has shown that male animals have worse outcome after TBI than female animals, and recent clinical trials have studied female sex hormones as a therapy for TBI.

Sex differences are understudied in preclinical research, and the National Institutes of Health has recently issued guidelines to ensure that sex and other biological variables are included in research design.

“It is really important to include both sexes in preclinical research in order to design better human clinical trials,” says Mark Burns, Ph.D., associate professor of neuroscience at GUMC and senior author of the study.

“When we looked to see if female mice had been included in TBI studies, we were surprised at what a blank slate we found,” Burns says. “Up to now, most preclinical studies of drugs to treat TBI have been conducted with young male mice — with variables such as age and sex being overlooked. You can’t develop a future of personalized medicine if you don’t include females in your research,” he adds.

The researchers focused on how sex alters key neuroinflammatory responses that follow TBI. They specifically looked at microglial cells, which are the resident immune cells of the brain, and movement of macrophages from the blood into the injured brain. Macrophages, which are also immune cells, offer the first line of defense against infection.

They found that the sex response was “completely divergent” up to a week after injury — there was a rapid activation of immune cells, along with robust neuron cell death, in males, but female mice experienced a markedly reduced response.

“It appears that female mice have more protection against brain trauma in the first week after TBI, and if that is true in humans it provides us with a much larger time-period to treat female patients following TBI. It will also help us design new treatments for TBI in males,” says Burns.

Burns also says that although the female mice have less of the negative effects of neuroinflammation such as neuron cell death, there are also positive aspects to neuroinflammation that are missing in female mice such as waste removal and wound healing. Understanding how to minimize the negative effects while maximizing the positive effects of inflammation is an important goal in TBI research.

“It is clear that further research is needed on sex differences in response to TBI — and now we have interesting leads to follow,” Burns says.

In addition to Burns, other authors include Sonia Villapol, PhD, assistant professor of neuroscience at GUMC and an expert on brain injury and neurodegeneration, and David Loane, PhD, an associate professor at the University of Maryland and an expert on neuroinflammation after brain injury.

Why does an anesthetic make us lose consciousness?

To date, researchers assumed that anesthetics interrupt signal transmission between different areas of the brain and that is why we lose consciousness. Neuroscientists at Goethe University Frankfurt and the Max Planck Institute for Dynamics and Self-Organization in Göttingen have now discovered that certain areas of the brain generate less information when under anesthesia. The drop in information transfer often measured when the brain is under anesthesia could be a consequence of this reduced local information generation and not — as was so far assumed — a result of disrupted signal Transmission between brain areas.

If only a few telephone calls are made in a city then it could be the case that several telecommunication systems have broken down — or it is nighttime and most people are asleep. The situation is similar in an anesthetized brain: if there is remarkably little information transfer between various areas of the brain then either signal transmission in the nerve fibers is blocked or certain areas of the brain are less active as far as the generation of information is concerned.

Patricia Wollstadt, Favio Frohlich, their colleagues from the Brain Imaging Center at Goethe University Frankfurt and researchers at the MPI for Dynamics and Self-Organization have now investigated this second hypothesis. As they have announced in the current issue of PLOS Computational Biology, they used ferrets to examine “source” brain areas from which less information was transmitted under anesthesia than in a waking state. They found out that information generation under anesthesia was far more affected there than in the “target” brain areas to which the information was transferred. This indicates that it is the information available in the source area which determines information transfer and not a disruption in signal transmission. Were the latter the case, a far greater reduction could be expected in the target areas since less information “arrives” there.

“The relevance of this alternative explanation goes beyond anesthesia research, says Patricia Wollstadt, “since each and every examination of neuronal information transfer should categorically take into consideration how much information is available locally and is therefore also transferable.”

Story Source:

Materials provided by Goethe University Frankfurt. Note: Content may be edited for style and length.

How blows to the head cause numerous small swellings along the length of neuronal axons

Researchers from The Ohio State University have discovered how blows to the head cause numerous small swellings along the length of neuronal axons. The study, “Polarity of varicosity initiation in central neuron mechanosensation,” which will be published June 12 in The Journal of Cell Biology, observes the swelling process in live cultured neurons and could lead to new ways of limiting the symptoms associated with concussive brain injuries.

Mild traumatic brain injuries, or concussions, cause a variety of temporary symptoms, including headache, nausea, and memory loss. But the effects of concussive impacts on neurons in the brain are poorly understood. One such effect is the development of “axonal varicosities,” small, bead-like swellings that appear along the length of neuronal axons, which are the parts of neurons that transmit electrical and chemical signals to neighboring nerve cells. Similar swellings are seen in the degenerating axons of Alzheimer’s and Parkinson’s patients.

Chen Gu and colleagues at The Ohio State University discovered that they could induce the formation of axonal varicosities in hippocampal neurons grown in the lab by “puffing” them with bursts of liquid from a small pipette. The pressure exerted by these puffs was similar to the forces neurons might experience after a blow to the head.

The axonal varicosities formed rapidly, particularly in younger neurons where they swelled up within 5 seconds of being puffed. A surprise to the researchers was that the varicosities disappeared several minutes after puffing, indicating that they are not a sign of irreversible axon degeneration.

Gu and colleagues could also induce axonal varicosities by repeatedly puffing cultured neurons with shorter bursts of liquid, mimicking the effects of repetitive, subconcussive impacts. Accordingly, the team also saw axonal varicosities in the brains of mice subjected to repeated light blows to the head.

The researchers found that puffing activated a mechanosensitive channel protein called TRPV4, which is enriched in the membrane of neuronal axons and allows calcium ions to enter the cell. Inhibiting this channel blocked the formation of axonal varicosities.

After entering axons through activated TRPV4 channels, calcium ions appear to disrupt the microtubule cytoskeleton by inhibiting a microtubule-stabilizing protein called STOP. This interrupts the transport of cellular materials along axonal microtubules, causing these materials to accumulate at several points along the axon where they may give rise to varicosities.

Older neurons, which are more resistant to the effects of puffing, express lower levels of TRPV4 and higher levels of STOP. “It will be interesting to determine whether these factors make a mature brain more resistant to mild traumatic brain injury than a young brain,” says Gu.

Puffing didn’t induce varicosities along the lengths of dendrites, the parts of neurons that receive chemical signals from neighboring nerve cells. Instead, the researchers found that dendritic, but not axonal, varicosities could be induced by prolonged treatment with glutamate, an excitatory neurotransmitter that is released from damaged axons.

“Taken together, our findings provide novel mechanistic insights into the initial stage of a new type of neuronal plasticity in health and disease,” says Gu, who points out that axonal varicosities have also been observed in healthy brains where neurons may respond to mechanical signals from their environment. “This process may therefore play a key role in neural development and central nervous system function in adults, as well as in chronic brain disorders and various acute brain injuries.”

Story Source:

Materials provided by Rockefeller University Press. Note: Content may be edited for style and length.

 

Radiation therapy vital to treating brain tumors, but it exacts a toll

Radiation therapy (RT) using high-energy particles, like x-rays or electron beams, is a common and critical component in successfully treating patients with brain tumors, but it is also associated with significant adverse effects, such as neuronal loss in adjacent healthy tissues.

In a new study, published in the June issue of Brain Connectivity, researchers at the University of California San Diego School of Medicine report that irradiation can cause broader adverse effects, altering the structural network properties in impacted brains and perhaps contributing to delayed cognitive impairments observed in many patients following brain RT.

“RT is a mainstay of brain tumor treatment,” said Naeim Bahrami, PhD, a postdoctoral fellow in the Center for Multimodal Imaging and Genetics at UC San Diego School of Medicine and first author of the study. “Unfortunately, a side effect can be incidental irradiation of normal brain tissue and radiation-induced injury, which have been linked to impairment of brain function. As patient outcomes improve, a major concern is managing long-term complications, including cognitive decline and disability.”

Previous research has shown that RT can affect discrete brain regions by causing cortical atrophy. In the new study, Bahrami and colleagues used complex mathematical models, such as graph theory, to look more broadly by estimating the thickness of the brain cortex in 54 patients with brain tumors before and after RT, using magnetic resonance imaging.

They found that RT produced both local and global changes in the structural network topology of the brain, thinning the cortex at a rate faster than that associated with Alzheimer’s disease, and increasing segregation between regions of the brain that typically work together to perform functions such as memory-making and recall.

Apart from adding new urgency to efforts to further refine RT and minimize adverse side effects, Bahrami said more research is needed to determine whether their topology-based technique might be useful in predicting or monitoring neurocognitive decline in patients following RT or other cancer-related therapies.

“Finding a non-invasive imaging biomarker to better assess cognitive function in the moment and in the future would be very helpful to clinicians,” Bahrami said.

Story Source:

Materials provided by University of California – San Diego. Note: Content may be edited for style and length.

 

Brain imaging reveals neural roots of caring

When others suffer, we humans empathize. Our feelings of empathy take different forms, such as distress when we imagine and internalize someone’s pain and compassion as we sympathize with their condition. These different feelings involve distinct patterns of brain activity, according to a study in Neuron published June 8. Feelings of empathy may seem subtle and personal, but this study, which used stories of human hardship to inspire feelings of empathic care and distress, found that the brain patterns associated with these feelings are consistent and predictable across individuals.

“Feelings of empathy are virtues we want to cultivate personally and in society,” says first author Yoni Ashar (@YoniAshar), a graduate student in the lab of Tor D. Wager (@torwager), professor of neuroscience at the University of Colorado, Boulder. “Understanding these emotions could open the doors to increasing empathy and compassion in personal relationships and on a broader societal level.”

Ashar has firsthand experience with empathic distress at home. When his toddlers start crying and fussing, sometimes he gets upset, too. “I’m mirroring them,” he says. “But I don’t need to meet them where they are. I can show compassion, or empathic care, instead.”

To study empathy, the researchers recruited 66 adults to sit in a brain scanner while listening to 24 true short stories of human distress. For instance, in one story, a young drug addict finds help at a boarding school and later is able to help others recover from addiction. Previous studies of empathy examined brain activity in response to static images flashed on a screen. “We took a naturalistic experimental approach that more closely resembles how we encounter the suffering of others in our daily lives,” says Ashar.

Using functional magnetic resonance imaging (fMRI), the researchers recorded brain activity patterns as subjects listened to the stories. The subjects heard the stories a second time outside the scanner, this time rating their feelings of distress and care over time as the narratives unfolded. The researchers then mapped the feelings to the patterns.

Brain activity associated with empathy was not rooted in one part of the brain, the way sensory input tends to be processed. Rather, it was spread across the brain and involved multiple brain regions. “The brain is not a modular system where there’s a region that manages empathy,” says Wager. “It’s a distributed process.”

Patterns associated with empathic care, for instance, overlapped with systems in the brain associated with value and reward, such as the ventromedial prefrontal cortex and the medial orbitofrontal cortex. In contrast, patterns of empathic distress overlapped with systems in the brain known for mirroring, such as the premotor cortex and the primary and secondary somatosensory cortices, which help an individual simulate or imagine what another person is feeling or thinking.

The patterns were surprisingly consistent from person to person, to the extent that the researchers could predict, based on brain activity, the feelings of an individual who had never been scanned before. “There is a personal element to when a person might feel empathic care or distress, but when you’re feeling them, you’re activating similar brain regions and brain systems as someone else might,” says Ashar.

In addition to performing brain scans, the researchers asked a separate group of 200 adults to listen to the stories and provide moment-by-moment ratings of their feelings, this time rating more basic feelings of sadness, disgust, anger, fear, negativity, positivity, and happiness. By mapping ratings of empathy to these ratings of more basic feelings, the researchers found that empathic care was associated with both happy and sad feelings, while empathic distress encompasses generally negative feelings of sadness, anger, fear, and disgust. “This suggests that empathic care, or compassion, reflects a blend of both warmth and distress,” says Ashar.

Empathic care is thought to inspire helpful behaviors, but empathic distress is thought by some to be a deterrent, initiating a desire to withdraw or turn away. To explore the influence of these different types of empathy on behavior, the study also asked subjects who underwent brain scans to donate portions of their payment for participation in the study. The study found that both forms of empathy increased the likelihood of charitable donations.

Empathic distress may influence giving, but it is also associated with negative emotions and burnout in caregivers and nurses. So Wager and colleagues are now investigating a 4-week meditation program designed to teach participants to empathize with others in ways that don’t increase distress but do increase care.

Story Source:

Materials provided by Cell Press. Note: Content may be edited for style and length.

 

Small group of neurons modulates the amount of insulin that the pancreas must produce

The brain is key in the regulation of appetite, body weight and metabolism. Specifically, there is a small group of hypothalamus neurons, called POMC, that detect and integrate signals that inform on the energy state of the organism and activate the appropriate physiological responses. These neurons are sensitive to fluctuations in nutrients such as glucose, fatty acids and amino acids.

Now, a research project co-chaired by Marc Claret, at the August Pi i Sunyer Biomedical Research Institute — IDIBAPS, and Antonio Zorzano, at the Institute for Research in Biomedicine (IRB Barcelona), both members of the CIBERDEM network, reveals the connection between POMC neurons at the hypothalamus and the release of insulin by the pancreas and describes new molecular mechanisms involved in this connection. The researchers publish the study in Cell Metabolism and the first authors are Sara Ramírez and Alicia G. Gómez-Valadés, both at IDIBAPS.

The connection between hypothalamus and pancreas

POMC neurons detect changes in nutrient availability, but the molecular mechanisms involved are not known in detail. Also changes in the shape of mitochondria, a phenomenon known as mitochondrial dynamics, is a mechanism of energy adaptation in changing metabolic conditions, to adjust the needs of cells.

To determine whether defects in the mitochondrial dynamics of this small nucleus of POMC neurons could cause alterations in metabolism, researchers removed a mitochondrial dynamics protein, Mitofusin 1, in these cells in mice.

First, the scientists observed that these mice have altered detection of glucose levels and adaptation between the fasting state and after being fed. Second, they found that these defects lead to disturbances in the glucose metabolism that are caused by a lower secretion of insulin.

“It was surprising to discover that these neurons are involved not only in the control of the intake, which was already known, but also in the control of the amount of insulin secreted by the beta cells of the pancreas,” explains Zorzano, Head of the Laboratory of Complex Metabolic Diseases and Mitochondria at IRB Barcelona.

Scientists observed for the first time that this communication between the hypothalamus and the pancreas depends on the activity of the protein Mitofusin 1 and are starting to understand some molecular details of this connection.

They describe that the alterations are due to a disproportionate, though transitory, increase in the production of radical oxygen species (ROS) in the hypothalamus. When the levels of ROS in the hypothalamus are restored in the laboratory, the pancreas starts to secrete the correct levels of insulin again.

Obesity and diabetes

Marc Claret, head of the Neuronal Metabolism Control Group at IDIBAPS, adds that “our results also suggest pathological implications of this animal model, since a diet rich in fats makes these mice more susceptible to developing diabetes.”

Insulin segregation is a major phenomenon in relation to diabetes. Type 2 diabetes patients, who represent the 85% of people with diabetes, have fewer beta cells and less ability to secrete insulin in response to glucose.

“Understanding the mechanisms involved in regulating insulin is important and therefore helps us to better understand the pathophysiology of diabetes,” says Claret, who emphasizes that “much research needs to be done to apply these findings, given that we are talking about neural mechanisms of complex intervention.”

 

A star is born: Lesser-known brain cell takes center stage

Neurons have long enjoyed the spotlight in neuroscience — and for good reason: they are incredibly important cellular actors. But, increasingly, star-shaped support cells called astrocytes are being seen as more than bit players in the brain’s rich pageant.

Salk researchers reported a new method of deriving astrocytes from stem cells, opening up broad avenues for research into diseases with inflammatory features. The protocol, which is described in the June 6, 2017, issue of Stem Cell Reports, offers a faster and more effective way to obtain astrocytes for brain research that could yield breakthroughs for treatments of such diverse conditions as stroke, Alzheimer’s or psychiatric disorders.

“This work represents a big leap forward in our ability to model neurological disorders in a dish,” says Salk Professor Rusty Gage, holder of the Vi and John Adler Chair for Research on Age-Related Neurodegenerative Disease and senior author of the paper. “Because inflammation is the common denominator in many brain disorders, better understanding astrocytes and their interactions with other cell types in the brain could provide important clues into what goes wrong in disease.”

Astrocytes are known to support neurons in a number of ways, from providing them with energy and physical scaffolding to cleaning up their waste. Astrocytes also have more general brain functions related to regulating blood flow and inflammation (a marker of injury or disease). But current methods to guide their development and differentiate them from human stem cells are time consuming and functionally limited. In the new paper, the Salk researchers describe a more efficient way to differentiate astrocytes that are sensitive to inflammation and function very much like ones in our brain do. Additionally, the Salk astrocytes can be co-cultured along with neurons, allowing researchers to model the interactions between these two important cell types in both healthy and diseased states.

With the right cocktails of chemicals — called growth factors — administered in stepwise fashion, human pluripotent stem cells can be prompted to develop into any cell type in the body. The Salk protocol guided pluripotent stem cells, over a period of six weeks, first to become generic neural cells and then precursors to astrocytes. With further chemical baths, the precursor cells differentiated into astrocytes a few weeks later.

“There are other methods for differentiating astrocytes, but our protocol arrives at inflammation-sensitive cells earlier, which makes modeling more efficient and straightforward,” says Carol Marchetto, a Salk senior staff scientist and one of the paper’s authors.

Another advantage of the Gage lab’s new method is that the astrocyte precursor cells can be frozen and later expanded and differentiated as needed, saving researchers approximately six weeks of time with each new experiment.

Tests revealed that the induced astrocytes functioned very much like astrocytes isolated from actual brain tissue. The lab-created astrocytes responded to the neurotransmitter glutamate and calcium similarly to natural astrocytes. Like typical astrocytes, the lab-generated cells also responded strongly to the presence of inflammatory molecules called cytokines by producing cytokines of their own.

Additionally, the team tested their protocol on induced pluripotent stem cells (iPSCs), which are adult cells, usually derived from skin, that have been reprogrammed to a stem-cell-like state. The lab successfully turned iPSCs into astrocytes that exhibited the same inflammation sensitivity the natural astrocytes did, providing an important resource for studying diseases where brain inflammation may play a role.

“This technique allows us to begin addressing questions about brain development and disease that we couldn’t even ask before,” says Gage. The team also co-cultured astrocytes derived from pluripotent stem cells with neurons, an important step in exploring the relationship of different brain-cell types to normal function and disease.

“The exciting thing about using iPSCs is that if we get tissue samples from people with diseases like multiple sclerosis, Alzheimer’s or depression, we will be able to study how their astrocytes behave, and how they interact with neurons,” says Krishna Vadodaria, a Salk research associate and one of the paper’s lead authors. This will be the next step in the lab’s research.

Story Source:

Materials provided by Salk Institute. Note: Content may be edited for style and length.

 

Brain damage can make sideways faces more memorable, and give us ’emotion blindness’

People with damage to a crucial part of the brain fail to recognise facial emotions, but they unexpectedly find faces looking sideways more memorable researchers have found.

The findings are more evidence that damage to the amygdala affects how facial recognition and gaze perception work in unpredictable ways. Perception and understanding the facial cues of others is essential in human societies.

Patients with amygdala damage, which is common in epilepsy for example, struggle in their understanding of social signals as well as in everyday communication, which can lead to problems in their interactions with friends and family, finding life partners, and progressing with their professional careers. They often feel misunderstood which contributes to lower levels of life satisfaction.

Normally we tend to more readily remember faces showing emotions such as fear or anger than neutral expressions. When trying to predict others’ actions, we decipher their facial expressions and follow their gaze to understand the focus of their attention and eventually of their emotion. This is an important process to understand the implications of the situation for our own well-being — which is known as self-relevance — and to interpret social situations and cues.

The amygdala is particularly responsible for the processing of emotion and self-relevance. Individuals with damage to the amygdala have been observed to have emotion recognition deficits while keeping the perception of others’ eye gaze direction intact.

But now researchers from the University of Bath, working with neurosurgeons and psychologists in Warsaw, Poland, have shown that individuals with amygdala damage remembered faces looking to the side more than those looking towards them — in contrast with previous studies.

However, in line with previous research they didn’t remember emotive faces any better than neutral faces.

Sylwia Hyniewska from the University of Bath said: “Surprisingly we found that individuals with amygdala damage remembered faces looking to the side more than those looking towards them. This effect was independent of the emotional content of the face. This was unexpected given that all research so far focusing on other populations showed either an interaction effect between emotion and gaze, or an improved memory for faces looking towards the observer.

“We expected our patients to remember faces better when they were looking at them — presented with the direct gaze. However for some reason patients seem to remember faces looking away better. This means that the interaction between the processing of emotions and gaze is more complex than we thought, and not only emotions but also gaze should be studied further in this specific population to develop treatments improving these patients’ well-being.”

The research is published in the journal Epilepsy and Behaviour.

The team showed 40 patients with mesial temporal lobe epilepsy (MTLE) and 20 healthy control patients a series of faces with neutral or emotional expressions. Half were looking straight ahead, and half sideways.

As expected healthy participants had better recognition of emotional faces. The epilepsy patients did not remember emotional faces any better than neutral ones, but did find patients gazing away more memorable than those looking straight ahead.

Story Source:

Materials provided by University of Bath. Note: Content may be edited for style and length.

 

Memory loss and other cognitive decline linked to blood vessel disease in the brain

Memory loss, language problems and other symptoms of cognitive decline are strongly associated with diseases of the small blood vessels in the brain, a study has found.

The study by senior author José Biller, MD, first author Victor Del Brutto, MD, and colleagues is published in the International Journal of Geriatric Psychiatry. Dr. Biller is chair of Loyola Medicine’s department of neurology. Dr. Del Brutto is a University of Chicago resident who did a neurology rotation at Loyola.

The study included 331 volunteers age 60 and older who live in Atahualpa, a small rural village in coastal Ecuador. The subjects were given cognitive tests and brain MRIs. The MRIs were examined for four main components of small vessel disease (SVD). These four components, which include evidence of microbleeds and minor strokes, then were added to create a total SVD score. The score ranges from zero points (no SVD) to 4 points (severe SVD).

The study found that that 61 percent of the subjects had zero points on the total SVD score, 20 percent had 1 point, 12 percent had 2 points, 5 percent had 3 points and 2 percent had 4 points. The higher the SVD score, the greater the cognitive decline. Researchers also found that each individual component of SVD predicted cognitive decline as well as the total SVD score did.

Cognitive decline was measured by a Spanish version of the Montreal Cognitive Assessment test. Subjects were asked to do basic cognitive tasks such as counting backwards from 100 by sevens, repeating back a list of words, identifying drawings of animals and naming in one minute as many words as possible that begin with N.

The finding that 39 percent of the older adults have at least one component of SVD indicates the condition is common in the region. This prevalence makes Atahualpa a suitable population for studying the effect of SVD on cognitive performance, researchers wrote.

SVD in the brain is a recognized cause of stroke and cognitive decline worldwide. The condition is an especial concern in Latin American countries, where it has been shown to be one of the most common mechanisms that cause strokes.

The study is part of the groundbreaking Atahualpa Project, a population-based study designed to reduce the increasing burden of strokes and other neurological disorders in rural Ecuador and similar communities in Latin America. Many Atahualpa residents have enrolled in studies of risk factors for common diseases, especially neurological and cardiovascular diseases. More than 95 percent of Atahualpa’s population belongs to the native/Mestizo ethnic group, and the villagers have similar diets and lifestyles, making them suitable subjects for population studies.

One of the SVD study’s authors, Mauricio Zambrano, is coordinator of the Atahualpa Project. Two other co-authors, Victor Del Brutto, MD, and Loyola vascular neurology fellow Jorge Ortiz, MD, are from Ecuador. The other co-authors are Atahualpa Project founder Oscar Del Brutto, MD, of the Universidad Espiritu Santo in Guayaquil, Ecuador and Robertino Mera, PhD, of the University of Vanderbilt Medical Center.

The study is titled, “Total cerebral small vessel disease score and cognitive performance in community-dwelling older adults. Results from the Atahualpa Project.”

Story Source:

Materials provided by Loyola University Health System. Note: Content may be edited for style and length.

 

Anticipation helps pathological gamblers hold out for larger-but-later rewards

Society for Neuroscience. “Anticipation helps pathological gamblers hold out for larger-but-later rewards.” ScienceDaily. ScienceDaily, 5 June 2017. .

Society for Neuroscience. (2017, June 5). Anticipation helps pathological gamblers hold out for larger-but-later rewards. ScienceDaily. Retrieved June 5, 2017 from www.sciencedaily.com/releases/2017/06/170605133536.htm

Society for Neuroscience. “Anticipation helps pathological gamblers hold out for larger-but-later rewards.” ScienceDaily. www.sciencedaily.com/releases/2017/06/170605133536.htm (accessed June 5, 2017).