​People often talk about their “gut instincts” or how they just “felt it in my guts” or that stress can give you “butterflies in the stomach” or make you nauseous to the point of vomiting.

Are these just figures of speech?

It turns out that the gut – the digestive system – has its own nervous system that is often referred to as our “second brain”. This “second brain” is called the enteric nervous system (ENS) and research is revealing that the ENS is in direct communication with the brain and the hypothalamic-pituitary-adrenal (HPA) axis (part of the central nervous system or CNS), the gut microbiota, the hormonal and the immune systems.

These are two-way communications systems, so that, for example, the microbiota – the combined pattern of microbes in the gut – can affect the stress response, the immune response, hormonal control of digestion and the predisposition to various conditions such as irritable bowel syndrome, obesity, diabetes, depression and anxiety. In turn, the ENS – and likely the CNS – can affect the pattern of bacteria in the microbiome as well as the digestive processes of the gut. However, it is becoming clearer that this is only the tip of the iceberg – the ENS, CNS and the microbiota can interact to produce dysfunction in the digestive, neurological, immune and hormonal systems, and to affect mental health.

The HPA axis is central in controlling the response to stress – and, as evidenced by the phrases like “my guts were tied in knots” or “I saw the accident and my stomach just dropped” – is both affected by and has effects on the ENS. The stress response – controlled in major part by the HPA axis – can be directly affected by abnormal gut bacteria early in life.

Serotonin (5HT) – a neurotransmitter sometimes called the “happiness hormone”, affecting mood, depression and anxiety – is found in its highest concentrations in the gut. A recent study from CalTech found that bacteria in the gut play a “critical role in regulating host 5-HT.” The microbiome is implicated in both anxiety and depression, disorders where 5-HT can play a critical role.

Recently, a systems biological model (the Brain-Gut-Microbiome or BGM model) was proposed that “posits circular communication loops amid the brain, gut, and gut microbiome, and in which perturbation at any level can propagate dysregulation throughout the circuit. A series of largely preclinical observations implicates alterations in brain-gut-microbiome communication in the pathogenesis and pathophysiology of irritable bowel syndrome, obesity, and several psychiatric and neurological disorders. Continued research holds the promise of identifying novel therapeutic targets and developing treatment strategies to address some of the most debilitating, costly, and poorly understood diseases.”

IBS and SIBO: Is there a connection?
Irritable bowel syndrome (IBS) is a common functional bowel disorder characterized by abdominal pain, cramping, bloating, gas, diarrhea, constipation or both. The abdominal pain and cramping are typically relieved by a bowel movement, that movement often producing a stool covered in mucus. Part of the underlying dysfunction in IBS is neurological. Diagnosis is often by exclusion as there is no specific diagnostic test for any form of IBS – diagnosis is based on the pattern of symptoms and the duration of the pattern. The Rome IV Criteria are used: “Recurrent abdominal pain, on average, at least 1 day per week in the last 3 months, associated with 2 or more of the following*:

• Related to defecation
• Associated with a change in frequency of stool
• Associated with a change in form (appearance) of stool

* Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis.

The causes of IBS remain unclear, though abnormal gastrointestinal (GI) motility and a disruption in the gut-brain axis (the BGM) appear to be at the root of IBS. It is often associated with depression and anxiety along with abnormalities in the microbiota. Risk factors for IBS include SIBO (see below), a history of viral or bacterial infections and abnormal motility of the small and large intestines.

Small Intestinal Bacterial Overgrowth (SIBO) is an excess of bacteria – sometimes methane-producing bacteria and more often with hydrogen-producing bacteria – in the small intestine – a portion of the digestive system that normally has few bacterial or other microbial residents. SIBO can lead to increased gas, diarrhea or constipation, abdominal pain, nausea and fatigue. Risk factors for SIBO include IBS, other GI disorders, and multiple courses of antibiotics. SIBO is believed to be related to dysfunction of small intestinal motility – the research community links IBS and SIBO because of the similarity of the symptoms with some believing that IBS is the primary event predisposing to SIBO where others believe just the opposite – that SIBO is the primary event predisposing to IBS. IBS patients with SIBO usually have to combine multiple different treatment options to manage and maintain health. Further research is needed to unravel the answers to this complex disorder.

A systems biology view of IBS and SIBO
IBS and SIBO are clearly related by symptoms and likely related mechanistically. The interconnectedness and bidirectionality of the Brain-Gut-Microbiome is currently being extensively studied – much more needs to be learned. Understanding the interactions will likely prove crucial to understanding functional digestive disorders and how stress can impact health.

While the initial cause(s) of IBS and SIBO are not known, it is becoming clearer that the gut, the brain and the microbiota communicate with each other – and that if this communication breaks down and becomes dysfunctional, dysfunction in the digestive, neurological, and immune system can become disrupted. Mental health may suffer as well as can sleep and the reactions to stress.

One should be cautious in applying pre-clinical information from model systems to clinical situations, yet maintaining a healthy microbiota has been clearly implicated in many conditions including functional digestive disorders such as SIBO and IBS, mood disorders, autism, obesity, addiction, allergic disorders, diabetes, cardiovascular diseases, conditions associated with aging and others.

As major technology firms race to roll out augmented reality products, Stanford researchers are learning how it affects people's behavior - in both the physical world and a digitally enhanced one.

In a new study led by Jeremy Bailenson, a professor of communication in the School of Humanities and Sciences, researchers found that after people had an experience in augmented reality (AR) - simulated by wearing goggles that layer computer-generated content onto real-world environments - their interactions in their physical world changed as well, even with the AR device removed. For example, people avoided sitting on a chair they had just seen a virtual person sit on. Researchers also found that participants appeared to be influenced by the presence of a virtual person in a similar way they would be if a real person were next to them. These findings are set to publish May 14 in PLOS ONE.

"We've discovered that using augmented reality technology can change where you walk, how you turn your head, how well you do on tasks, and how you connect socially with other physical people in the room," said Bailenson, who co-authored the paper with graduate students Mark Roman Miller, Hanseul Jun and Fernanda Herrera, who are the lead authors.​

Particularly, the group of "Neurochemistry of the Transmission in the Central Nervous System", co-directed by Professor Zaida Díaz-Cabiale, has evidenced that a fragment of the "Galanin" neuropeptide -an endogenous molecule of the brain- is involved in anhedonia, which is the loss of the capacity to feel pleasure in daily activities, for instance, meals, social activity or sex, and, thus, one of the main symptoms in depressed patients.

These researchers have demonstrated for the first time the role of "GAL (1-15)" in the brain reward system of an animal model.

"We have verified through different experiments how animals modify their response to high-reinforcement appetitive stimuli, such as saccharine or sexual attraction, after the administration of the Galanin fragment", explains researcher Carmelo Millón, one of the authors of this study, published in Journal of Psychopharmacology.

Furthermore, in this article, in which a researcher of Karolinska Institute (Sweden) has participated, they have analyzed the brain reinforcement system at a molecular level, the circuit in charge of reinforcing positive behavior for individuals and species, and reaffirmed that the Galanin fragment acts directly on this neurological mechanism, reducing the circuit activity.

According to Millón, describing this fragment is essential to modulate the brain reward circuit, having interesting applications that go beyond treatments for depression, such as its possible use in drug-related addictions. "The understanding of these mechanisms opens the way for endless therapeutic strategies, hence its importance", he says.

The research group of "Neurochemistry of the Transmission in the Central Nervous System" has been studying the Galanin molecule for more than two decades, originally in cardiovascular regulation. Its role in neuropsychiatric diseases, such as depression or anxiety, started to be investigated in the UMA in 2007.

This article has been republished from materials provided by the University of Malaga. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference: 
Carmelo Millón et al. Role of the galanin N-terminal fragment (1-15) in anhedonia: Involvement of the dopaminergic mesolimbic system, Journal of Psychopharmacology (2019). DOI: 10.1177/0269881119844188

A Columbia University study has found that adversity early in life is associated with increased gastrointestinal symptoms in children that may have an impact on the brain and behavior as they grow to maturity.

The study was published online March 28 in the journal Development and Psychopathology.

“One common reason children show up at doctors’ offices is intestinal complaints,” said Nim Tottenham, a professor of psychology at Columbia and senior author on the study. “Our findings indicate that gastrointestinal symptoms in young children could be a red flag for future emotional health problems.”

Scientists have long noted the strong connection between the gut and brain.

Previous research has demonstrated that a history of trauma or abuse has been reported in up to half of adults with irritable bowel syndrome (IBS), at a prevalence twice that of patients without IBS.

“The role of trauma in increasing vulnerability to both gastrointestinal and mental health symptoms is well established in adults but rarely studied in childhood,” said study lead author Bridget Callaghan, a post-doctoral research fellow in Columbia’s psychology department. In addition, she said, animal studies have demonstrated that adversity-induced changes in the gut microbiome – the community of bacteria in the body that regulates everything from digestion to immune system function–influence neurological development, but no human studies have done so.

“Our study is among the first to link disruption of a child’s gastrointestinal microbiome triggered by early-life adversity with brain activity in regions associated with emotional health,” Callaghan said.  

The researchers focused on development in children who experienced extreme psychosocial deprivation due to institutional care before international adoption. Separation of a child from a parent is known to be a powerful predictor of mental health issues in humans. That experience, when modeled in rodents, induces fear and anxiety, hinders neurodevelopment and alters microbial communities across the lifespan.

The researchers drew upon data from 115 children adopted from orphanages or foster care on or before approximately they were 2 years old, and from 229 children raised by a biological caregiver. The children with past caregiving disruptions showed higher levels of symptoms that included stomach aches, constipation, vomiting and nausea.

From that sample of adoptees, the researchers then selected eight participants, ages 7 to 13, from the adversity exposed group and another eight who’d been in the group raised by their biological parents. Tottenham and Callaghan collected behavioral information, stool samples and brain images from all the children. They used gene sequencing to identify the microbes present in the stool samples and examined the abundance and diversity of bacteria in each participant’s fecal matter.

The  children with a history of early caregiving disruptions had distinctly different gut microbiomes from those raised with biological caregivers from birth. Brain scans of all the children also showed that brain activity patterns were correlated with certain bacteria. For example, the children raised by parents had increased gut microbiome diversity, which is linked to the prefrontal cortex, a region of the brain known to help regulate emotions.

“It is too early to say anything conclusive, but our study indicates that adversity-associated changes in the gut microbiome are related to brain function, including differences in the regions of the brain associated with emotional processing,” says Tottenham, an expert in emotional development. 

More research is needed, but Tottenham and Callaghan believe their study helps to fill in an important gap in the literature.

“Animal studies tell us that dietary interventions and probiotics can manipulate the gut microbiome and ameliorate the effects of adversity on the central nervous system, especially during the first years of life when the developing brain and microbiome are more plastic,” Callaghan says. “It is possible that this type of research will help us to know if and how to best intervene in humans, and when.”

Callaghan and Tottenham are currently working on a larger-scale study with 60 children in New York City to see if their findings can be replicated. They expect the results later this year.           

This article has been republished from materials provided by Columbia University. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference: Callaghan, B. L., Fields, A., Gee, D. G., Gabard-Durnam, L., Caldera, C., Humphreys, K. L., … Tottenham, N. (undefined/ed). Mind and gut: Associations between mood and gastrointestinal distress in children exposed to adversity. Development and Psychopathology, 1–20. https://doi.org/10.1017/S0954579419000087

Exercise might not be fun, but it’s good for your body. Over the years, science has well established that exercise can cut your risk of cardiovascular disease, type 2 diabetes, and some types of cancer. But the ways that exercise affects the brain are still under investigation, although new research suggests it may be essential for the growth of new neurons. 

Research conducted at the Università degli Studi di Milano (University of Milan) examined the effect of restricting mice from using their hind, but not their front legs, for a period of 28 days. The paper detailing the research was published in Frontiers in Neuroscience. Whilst the mice were able to eat and groom themselves as normal, and didn’t show signs of being stressed, subsequent analysis showed significant changes in the mice’s brains, including impairment of the mice’s neural stem cells. The researchers noted that the number of neural stem cells – which produce all neurons and glia during development and persist in certain areas into adulthood – that were actively producing new neurons was reduced by 70% in the restricted mice as compared to mice that hadn’t had their movement restricted.   ​

The muscles of mice
​How our nervous system controls our muscular responses is well understood. Chemical signals released from motor neurons activate receptors located on muscle membranes. This opens ion channels, triggering an electrochemical cascade that ultimately leads to contraction of the muscle fiber. What the Italian study authors found is that the mice’s muscles might be influencing the nervous system in return. 

“The main findings of our paper are that the reduction of movement alters the neurogenic capabilities at least in one area of the mouse brain, the sub ventricular zone. These alterations include a reduced capability to proliferate in vitro and in vivo, a lower capability to produce new neurons in vitro, an altered cell metabolism and specific gene expression modifications,” say Raffaella Adami and Daniele Bottai, authors of the paper and researchers at the University of Milan’s Department of Health Science.

So how exactly are these muscle movements having their effect? “In response to the contraction, the muscle produces and releases several factors (myokines), extracellular vesicles (exosomes), and metabolites that could reach and activate several organs. These factors could act locally, and have a paracrine effect on neurons, or be transported in serum and pass the blood-brain barrier. Among the myokines, brain derived neurotrophic factor (BDNF) is an important factor for the activation of neurons and neuronal stem cells. BDNF could be also released by neuronal cells when excited or under specific myokine stimulation, in a close cross-talk between muscle exercise and nervous effect,” say Bottai and Adami.

​Can exercise battle neurodegeneration?
The authors point out that although the phrase Mens sana in corpore sano (roughly “A healthy mind in a healthy body”) has been around since the Roman poet Juvenal first wrote it down in the early second century (his original meaning has been somewhat taken out of context), modern research has increased interest in how modifiable lifestyle factors may help slow or prevent progression of neurodegenerative diseases like Alzheimer's disease (AD). A 2014 paper which examined 317 members of the Wisconsin Registry for Alzheimer's Prevention showed associations between physical activity and improvement in several AD-related factors, including β-amyloid burden, glucose metabolism, and hippocampal volume. 

Whilst meta-analyses such as these have established that there is a role for exercise in improving age-related cognitive decline, a definite explanation for this effect is as yet missing. Bottai and Adami’s research in mice is part of a large body of work in animals that suggest potential mechanisms for exercise-mediated neuroprotection, but the evidence from human studies is less concrete. A recent Consensus Study Report by the National Academies of Science (as definitive an authority as you get in science) was unable to definitively recommend that exercise could reduce dementia risk due to the inconsistencies in results from human studies.

​Next Steps
​To establish a concrete evidence base in humans, more research will need to be done. For Bottai and Adami, the way forward is clear: “Our studies are continuing trying to depict some molecular aspects that we started to investigate in the first work. Currently, we are evaluating deeply the gene expression change induced by exercise restriction. Indeed, many researchers are studying the opposite effect, how exercise could improve the cognitive and psychological condition in impaired status.” 

Whilst animal studies are an important first step in biomedical research, Bottai and Adami know that the human brain is a real step up in complexity. How might their own findings affect clinical outcomes in patients with neurodegenerative disease? “It is too early to formulate any conclusion from our data about this point. For sure the reduction of neurogenic capability could interfere with brain function in brain patients. However, the human brain is much more complicated than the mouse brain and the niches where neural stem cells are located are much more diffused than in rodents," say the researchers.

In summary then, exercise seems to have some pretty positive effects on the mammalian brain, but we don't have enough evidence to say that exercise is a sure-fire way of preventing diseases like dementia in humans, although studies point towards exercise reducing risk. Given the other numerous health benefits of going for a run, and the complete lack of evidence that sitting on the sofa and eating nachos will cut your disease risk, it seems regular exercise remains key to a healthy life, for brain and body.

At work, it’s healthier and more productive just to be yourself, according to a new study from Rice University, Texas A&M University, the University of Memphis, Xavier University, Portland State University and the University of California, Berkeley.

The study, “Stigma Expression Outcomes and Boundary Conditions: A Meta-Analysis” will appear in an upcoming edition of the Journal of Business and Psychology. It examines 65 studies focusing on what happens after people in a workplace disclose a stigmatized identity, such as sexual orientation, mental illness, physical disability or pregnancy.

Eden King, a co-author of the study and an associate professor of psychology at Rice, said the decision to express a stigmatized identity is highly complicated.

“It has the potential for both positive and negative consequences,” she said.

However, the research overwhelmingly indicates that people with non-visible stigmas (such as sexual orientation or health problems) who live openly at work are happier with their overall lives and more productive in the workplace. King said self-disclosure is typically a positive experience because it allows people to improve connections, form relationships with others and free their minds of unwanted thoughts.

Workers who expressed their non-visible stigmas experienced decreased job anxiety, decreased  role ambiguity, improved job satisfaction and increased commitment to their position. Outside of work, these workers reported decreased psychological stress and increased satisfaction with their lives.

But the study found that the same results did not apply to people with visible traits, such as race, gender and physical disability.

“Identities that are immediately observable operate differently than those that are concealable,” King said. “The same kinds of difficult decisions about whether or not to disclose the identity — not to mention the questions of to whom, how, when and where to disclose those identities — are probably less central to their psychological experiences.”

King said that because most people appreciate gaining new information about others, the expression of visible stigmas is likely to be less impactful.

“Also, people react negatively to those who express or call attention to stigmas that are clearly visible to others, such as race or gender, as this may be seen as a form of advocacy or heightened pride in one’s identity,” she said.

The researchers said more work needs to be done to understand the motivations for expressing different stigmas. They hope this meta-analysis will be used to help workplaces and policymakers protect individuals with stigmas from discrimination.

This article has been republished from materials provided by Rice University. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference: Sabat, I. E., Lindsey, A. P., King, E. B., Winslow, C., Jones, K. P., Membere, A., & Smith, N. A. (2019). Stigma Expression Outcomes and Boundary Conditions: A Meta-Analysis. Journal of Business and Psychology. https://doi.org/10.1007/s10869-018-9608-z

Researchers removed vitamin D from the diet of a group of healthy adult mice, and after 20 weeks found a significant decline in their ability to remember and learn compared to a control group.

Dr Burne said the vitamin D deficient group had a pronounced reduction in perineuronal nets in the hippocampus, the brain region crucial to memory formation.

“There was also a stark reduction in both the number and strength of connections between neurons in that region.”

UQ researchers propose that when vitamin D levels drop, certain enzymes become unchecked and begin to break down perineuronal nets. (Nick Valmas, UQ)Dr Burne’s team propose that vitamin D plays an important role in keeping perineuronal nets stable, and that when vitamin D levels drop, this ‘scaffolding’ is more easily degraded by enzymes.

“As neurons in the hippocampus lose their supportive perineuronal nets, they have trouble maintaining connections, and this ultimately leads to a loss of cognitive function.”

Associate Professor Burne said the hippocampus may be most strongly affected by vitamin D deficiency because it is much more active than other brain regions.

“It’s like the canary in the coalmine—it might fail first because its high energy requirement makes it more sensitive to the depletion of essential nutrients like vitamin D.

“Intriguingly, the right side of the hippocampus was more affected by vitamin D deficiency than the left side.”

Associate Professor Burne said loss of function in this area could be an important contributor to the hallmarks of schizophrenia, including severe memory deficits and a distorted perception of reality.

“The next step is to test this new hypothesis on the link between vitamin D deficiency, perineuronal nets and cognition,” he said.

“We are also particularly excited to have discovered these nets can change in adult mice.

 “I’m hoping that because they’re dynamic there is a chance that we can rebuild them, and that could set the stage for new treatments.”

This article has been republished from materials provided by the University of Queensland. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference: Mayne, P. E., & Burne, T. H. J. (2019). Vitamin D in Synaptic Plasticity, Cognitive Function, and Neuropsychiatric Illness. Trends in Neurosciences, 0(0). https://doi.org/10.1016/j.tins.2019.01.003

What’s an s-shaped animal with scales and no legs?  What has big ears, a trunk and tusks? What goes ‘woof’ and chases cats? The brain’s ability to reconstruct facts – ‘a snake’, ‘an elephant’ and ‘a dog’ – from clues has been observed using brain scanning by researchers at Aalto university. Their study was published today in Nature Communications.

In the research, test subjects were given three clues to help them guess what familiar objects the clues described. In addition to well-known animals, the clues depicted vegetables, fruits, tools and vehicles. The familiar objects and concepts described in the clues were never presented directly to the test subjects.

The researchers at Aalto University demonstrated that brain activation patterns contained more information about the features of the concept than had been presented as clues. The researchers concluded that the brain uses environmental clues in an agile way to activate a whole range of the target concept’s properties that have been learned during life.

‘This is a very important skill in nature because it enables a quick response based on small amount of information. For example, we automatically avoid a wiggly thing on a rocky shore because we know that a snake may be poisonous,’ says Sasa Kivisaari, Postdoctoral Researcher at the Aalto University.

The study used a huge amount of internet-based material to map the meaningful features associated with different concepts. Machine learning was used to create a model that describes the relationship between these features and brain activation patterns. Based on the model, brain activation patterns could be used to accurately deduce which concept the test subject was thinking of. For example, the activation patterns could be used to infer whether the clues led the subject to think of an elephant or a dog.

Understanding our differences to detect memory disorders
The method can be used to address the question why people understand or perceive the same concept differently.

‘The organization of meanings in the brain differs from person to person and can also affect how easy or hard it is for them to understand each other,’ says Professor Riitta Salmelin.

The research may also play a role in detecting memory disorders.

‘Combining and understanding meaningful information seems to involve the same brain areas that are damaged in early Alzheimer's disease. Therefore, the method we use may also be applied to the early detection of memory disorders,’ says Kivisaari.

Professor Riitta Salmelin's research team studies the neural basis of processing of language and meaningful information at the Department of Neuroscience and Biomedical Engineering at Aalto University. The research has been supported by the Academy of Finland, the Aalto Brain Centre and the Sigrid Jusélius Foundation.

This article has been republished from materials provided by Aalto University. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference: Kivisaari, S. L., Vliet, M. van, Hultén, A., Lindh-Knuutila, T., Faisal, A., & Salmelin, R. (2019). Reconstructing meaning from bits of information. Nature Communications, 10(1), 927. https://doi.org/10.1038/s41467-019-08848-0‘This is a very important skill in nature because it enables a quick response based on small amount of information. For example, we automatically avoid a wiggly thing on a rocky shore because we know that a snake may be poisonous,’ says Sasa Kivisaari, Postdoctoral Researcher at the Aalto University.