Why Autistic Kids Avoid Eye Contact

"The findings demonstrate that, contrary to what has been thought, the apparent lack of interpersonal interest among people with autism is not due to a lack of concern," says Nouchine Hadjikhani, MD, PhD, director of neurolimbic research in the Martinos Center and corresponding author of the new study. "Rather, our results show that this behavior is a way to decrease an unpleasant excessive arousal stemming from overactivation in a particular part of the brain."
Individuals with autism spectrum disorder (ASD) often find it difficult to look others in the eyes. This avoidance has typically been interpreted as a sign of social and personal indifference, but reports from people with autism suggests otherwise. Many say that looking others in the eye is uncomfortable or stressful for them - some will even say that "it burns" - all of which points to a neurological cause. Now, a team of investigators based at the Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital has shed light on the brain mechanisms involved in this behavior. They reported their findings in a Scientific Reports paper published online this month.
The key to this research lies in the brain's subcortical system, which is responsible for the natural orientation toward faces seen in newborns and is important later for emotion perception. The subcortical system can be specifically activated by eye contact, and previous work by Hadjikhani and colleagues revealed that, among those with autism, it was oversensitive to effects elicited by direct gaze and emotional expression. In the present study, she took that observation further, asking what happens when those with autism are compelled to look in the eyes of faces conveying different emotions.
Using functional magnetic resonance imaging (fMRI), Hadjikhani and colleagues measured differences in activation within the face-processing components of the subcortical system in people with autism and in control participants as they viewed faces either freely or when constrained to viewing the eye-region. While activation of these structures was similar for both groups exhibited during free viewing, overactivation was observed in participants with autism when concentrating on the eye-region. This was especially true with fearful faces, though similar effects were observed when viewing happy, angry and neutral faces.
The findings of the study support the hypothesis of an imbalance between the brain's excitatory and inhibitory signaling networks in autism - excitatory refers to neurotransmitters that stimulate the brain, while inhibitory refers to those that calm it and provide equilibrium. Such an imbalance, likely the result of diverse genetic and environmental causes, can strengthen excitatory signaling in the subcortical circuitry involved in face perception. This in turn can result in an abnormal reaction to eye contact, an aversion to direct gaze and consequently abnormal development of the social brain.
In revealing the underlying reasons for eye-avoidance, the study also suggests more effective ways of engaging individuals with autism. "The findings indicate that forcing children with autism to look into someone's eyes in behavioral therapy may create a lot of anxiety for them," says Hadjikhani, an associate professor of Radiology at Harvard Medical School. "An approach involving slow habituation to eye contact may help them overcome this overreaction and be able to handle eye contact in the long run, thereby avoiding the cascading effects that this eye-avoidance has on the development of the social brain."
The researchers are already planning to follow up the research. Hadjikhani is now seeking funding for a study that will use magnetoencephalography (MEG) together with eye-tracking and other behavioral tests to probe more deeply the relationship between the subcortical system and eye contact avoidance in autism.
Source: MASSACHUSETTS GENERAL HOSPITAL
The co-authors of the Scientific Reports study are Nicole R. Zürcher, Amandine Lassalle and Noreen Ward of the MGH Martinos Center; Jakob Åsberg Johnels, Eva Billstedt and Christopher Gillberg of Gothenburg University, Gothenburg, Sweden; Quentin Guillon of the Lyon Neuroscience Research Center, Lyon, France; Loyse Hippolyte of the University of Lausanne, Lausanne, France; and Eric Lemonnier of CRA, of Limoges, France. The study was supported by the Swiss National Science Foundation (grant PP00P3-130191), the Centre d'Imagerie BioMédicale of the University of Lausanne, as well as the Foundation Rossi Di Montalera, the LifeWatch Foundation, the AnnMarie and Per Ahlqvist Foundation, the Torsten Soderberg Foundation and the Swedish Science Council.
The MGH Research Institute conducts the largest hospital-based research program in the nation, with an annual research budget of more than $800 million and major research centers in HIV/AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, genomic medicine, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, photomedicine and transplantation biology.

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Diet effect on Alzheimer's gene carriers

Is there a real link between what we eat and onset of a disease such as Alzheimer's? Does obesity click some of the genes associated with neurodegenerative disorders? A diet high in cholesterol, fat and sugar may influence the development of Alzheimer's disease in people who carry the ApoE4 gene, a leading risk factor for the memory-erasing disease, indicates a new USC study. The study on mice, published June 12 in the journal eNeuro, is the latest to explore the association between obesity and Alzheimer's disease, both of which are associated with inflammation and both of which affect millions of people.

For the study, researchers at the USC Davis School of Gerontology compared the effects of a poor diet on groups of mice that either had the Alzheimer's-associated ApoE4 gene or the relatively benign variant of the gene, ApoE3. After eating an unhealthy diet, the mice with the ApoE4 gene showed more Alzheimer's plaques - a marker for inflammation - in their brains, but those with ApoE3 did not.

"Part of what the results are saying is that risk doesn't affect everybody the same, and that's true for most risk factors," said Christian Pike, the lead author of the study and a professor for the USC Davis School of Gerontology. "Your genes have a big role in what happens to you, but so does your environment and your modifiable lifestyle factors. How much you exercise becomes important and what you eat becomes important."

Alzheimer's and obesity are among the intractable problems that USC researchers in multiple disciplines are seeking to unravel.

Both are widespread and costly. An estimated 5.4 million Americans have Alzheimer's, which costs an estimated $286 billion a year. The USC Schaeffer Center for Health Policy and Economics predicts the number of U.S. patients diagnosed with Alzheimer's will more than double to 9.1 million in the next 35 years. By then, total care costs will top $1.5 trillion.

An estimated 72 million American adults are obese - representing about 30 percent of the nation's adult population, according to the Centers for Disease Control and Prevention. Annual health care costs for obesity in the United States range between $147 billion to $210 billion.

As a research institution devoted to promoting lifelong health, USC has more than 70 researchers across a range of disciplines who are examining the health, societal and political effects and implications of the disease. In the past decade, the National Institute on Aging has nearly doubled its investment in USC research. The investments include an Alzheimer Disease Research Center.

ApoE4 and ApoE3 are two variants of a gene that codes for a protein, apolipoprotein E, which binds fats and cholesterol to transport them to the body's lymphatic and circulatory systems and to the brain. The ApoE4 variant is linked to increased inflammation, Alzheimer's and cardiovascular disease.

ApoE3, which does not increase risk for the disease, is much more common variant, appearing in an estimated 70 to 75 percent of the population. ApoE4 appears in around 10 to 15 percent of the population.

Science has shown that Alzheimer's affects more women than men. Having one copy of ApoE4 quadruples women's risk for developing the disease. But having two copies of ApoE4 is an issue for men and women, raising their risk for the disease by a factor of 10.

Still, some people with ApoE3 and ApoE4 never develop Alzheimer's. Knowing this, Pike wanted to explore whether obesity and diet, in the presence of either gene, would affect the disease's development.

For 12 weeks, a group of mice with ApoE4 were placed on a control diet that was 10 percent fat and 7 percent sucrose, while another group of mice with ApoE4 ate a Western diet that was of 45 percent fat and 17 percent sucrose. A similar test was run on mice with ApoE3.

On the unhealthy diet, both the mice with ApoE4 and those with ApoE3 gained weight and became pre-diabetic. But most significantly, those with ApoE4 on the unhealthy diet quickly developed the signature plaques that obstruct cognition and memory.

However, Alzheimer's symptoms did not worsen for the ApoE3 mice that ate a Western diet.

"What happens to you in life is a combination of the genes that you have, the environment and behaviors, such as diet," Pike said. "Our thinking is that the risk of Alzheimer's associated with obesity is going to be regulated to some degree by the genes that we have."

The results in the mice indicate a relationship between diet and the growth of plaques and other signs of brain inflammation for mice with ApoE4.

Pike said further study is needed to understand the relationship between the two. Research already has shown that even a brief spate of poor diet can inflame glia, the brain cells responsible for immunity response.

"That means there are probably components directly in the diet, and one of those are fatty acids, like palmitic acid, that trigger inflammation because they can go in and directly affect glia," Pike said. "But that may be just one inflammation-related component of Alzheimer's disease."

"There's probably a variety of different signals that affect the brain," he added. "People even suggest that signals coming from the gut - the microbiome - are influential."

Pike noted that women and men with risk factors for Alzheimer's may also respond differently to the effects of diet - an issue worth further exploration, he said.

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The study was co-written by Alexandra Moser, a Ph.D. student in the USC Neuroscience Graduate Program.

Ninety percent of the study was supported by National Institutes of Health grant AG034103. The five-year $1.6 million grant awarded in 2011. Ten percent of the study was covered by another NIH grant, AG051521. The five-year $3 million grant was awarded in 2015. Both grants cover several research studies.

Source: NIH

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Genome-wide DNA damage from Cigarette Smoking

Innovation comes from the laboratory of Nobel laureate Aziz Sancar, MD, PhD, the Sarah Graham Kenan Professor of Biochemistry and Biophysics at UNC's School of Medicine. In a study published in the Proceedings of the National Academy of Sciences, Sancar and his team developed a useful technique for mapping sites on the genome that are undergoing repair following a common type of DNA damage. They then used that technique to map all damage caused by the major chemical carcinogen - benzo[α]pyrene. Scientists have known for decades that smoking cigarettes causes DNA damage, which leads to lung cancer. Now, for the first time, this technique effectively map the DNA damage at high resolution across the genome.
"This is a carcinogen that accounts for about 30 percent of the cancer deaths in the United States, and we now have a genome-wide map of the damage it causes," Sancar said.
Maps like these will help scientists better understand how smoking-induced cancers originate, why some people are more vulnerable or resistant to cancers, and how these cancers might be prevented. Sancar also hopes that providing such stark and specific evidence of smoking's harm at the cellular level might induce some smokers to kick the habit. There are about 40 million smokers in the United States and a billion worldwide.
"It would be good if this helps raise awareness of how harmful smoking can be," he said. "It also would be helpful to drug developers if we knew exactly how DNA damage is repaired throughout the entire genome."
BaP: Earth's Top Chemical Carcinogen?
Benzo[α]pyrene (BaP) is a member of a family of simple, hardy, carbon-rich hydrocarbons - polycyclic aromatic hydrocarbons - that can form even in outer space. Scientists think these molecules might have seeded simple carbon-based life on Earth and other planets. But for more evolved and complex DNA-based life forms - humans for example - BaP poses a serious environmental hazard. It's a byproduct of burning organic compounds, such as tobacco plants. Everyday forms of combustion, from forest fires to diesel engines and barbecue grills, put a lot of BaP into our air, soil, and food. But nothing in ordinary life delivers it into human tissue more efficiently than puffing on a lit cigarette.
Typically, when a toxic hydrocarbon gets into a person through breathing or eating, enzymes in our blood break it down into smaller, safer molecules. That happens for BaP, too, but the protective reactions also yield a compound called benzo[α]pyrene diol epoxide (BPDE), which turns out to be worse than BaP itself.
BPDE reacts chemically with DNA, forming a very tight bond at the nucleobase guanine. This bond, or adduct, means that the genes can no longer make proper proteins and DNA can't be duplicated properly during cell division. And if that happens, disease can be the result.
"If a BPDE adduct occurs in a tumor suppressor gene and isn't repaired in a timely manner, it can lead to a permanent mutation that turns a cell cancerous," said Wentao Li, PhD, a postdoctoral researcher and lead author of the study.
There is no doubt about the basic carcinogenicity of chemical reaction. Paint a moderate dose of BaP on the skin of a lab mouse, and tumors are almost certain to erupt. BaP, via BPDE, has long been recognized as a promoter of multiple types of cancer and is considered the single most important cause of lung cancer.
Repairs underway
Sancar's new method for mapping BaP-induced DNA damage enables scientists to identify the sites on the genome where cells are trying to repair the damage. Sancar won a share of the 2015 Nobel Prize for Chemistry for teasing apart the detailed workings of this biochemical repair process.
Known as nucleotide excision repair, it involves the recruitment of special proteins that perform DNA surgery. They snip out the affected strand of DNA. If all goes well, DNA-synthesizing enzymes then reconstruct the missing section of DNA from another unaffected strand. This is possible because all cell-based life forms on Earth have two complementary strands of DNA. Meanwhile, the snipped-out damaged section of DNA floats free until garbage-disposal molecules eventually degrade it.
Those free-floating bits of damaged DNA may be garbage to the cell, but they are solid gold for a scientist who wants to map all damage in a genome. With the new method, scientists can tag and collect these cast-off snippets, sequence them, and then fit together their sequences - like tiny pieces of a giant puzzle - to create a map of the genome. In the end, scientists have a complete map of the sites where repairs to damaged DNA have begun.
Given the effort and expense required for DNA sequencing, the initial, proof-of-principle map published by Sancar, Li and colleagues doesn't have the highest resolution possible. But it points the way towards the routine scientific use of such maps, especially as costs drop, to better understand how DNA-damaging events lead to disease and death.
This mapping technique should help answer several questions, such as:
  • What dose of a toxin is needed to overwhelm the average person's nucleotide excision repair capacity?
  • Which variations - and in which genes - give people more or less capacity to repair such DNA damage?
  • Are there certain spots on the genome where successful repairs are inherently less likely?
Even with their initial, medium-resolution map, Sancar and colleagues were able to show that repairs of BPDE damage tend to occur more often when the BPDE-burdened guanine (G) is next to a cytosine (C) rather than a thymine (T) or adenine (A). This suggests there are "hotspots" of higher risk for BPDE-induced mutation.
"Understanding this bias in repair should help us better understand why exposures to toxins such as BaP tend to cause certain gene mutations," Li said.
Looking forward
In studies published in 2015 and 2016, Sancar and colleagues used earlier versions of their technique to map two other types of DNA-adduct damage: one wrought by ultraviolet light and the other by the common chemo drug cisplatin. Those mapping studies required an extra chemical step - removing the damage from an excised snippet before sequencing it - because the DNA-reading enzyme needed for the sequencing process would otherwise get stuck at the adduct. In contrast, the new technique employs "translesional" enzymes with dimensions that allow it to keep reading a strand of DNA even when a bulky BPDE adduct is present.
"This new method can be applied to any type of DNA damage that involves nucleotide excision repair," Sancar said.
Sancar, Li, and their colleagues are now using the new technique to map DNA damage repair associated with other environmental toxins. Their next project focuses on aflatoxins, a family of mold-produced molecules often found in poorly stored nuts and grains. These toxins damage DNA and are major causes of liver cancer in developing countries.
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The researchers are also performing more studies to uncover factors influencing where and whether nucleotide excision DNA repair occurs. To do that, they need to map sites of actual damage on the genome itself, not just the damaged snippets that are excised during repairs.
In one such project, they have developed a sensitive, high-resolution method for mapping actual DNA damage caused by ultraviolet light. By combining that method with repair mapping, they have found that the UV damage to DNA appears to be essentially uniform, although the repair process is not. Repair seems to be affected by a host of factors, including how actively a given stretch of DNA is being copied out to encode the making of proteins. They are currently applying this method to BaP to complement the repair map they have generated.
That again points to the likelihood of hotspots where repair is less likely to occur and mutations are more likely to arise.
"I'm certain," said Sancar, "that all this information will lead to a better understanding of why certain people are predisposed to cancer, and which smoking-related mutations lead to lung cancer specifically."

And that, in turn, could have implications for the development of more targeting therapies down the line.
Source: UNIVERSITY OF NORTH CAROLINA HEALTH CARE

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Brain Benefits From Simple Physical Activity

There is currently enormous interest in the beneficial effects of aerobic exercise on a wide range of brain functions including mood, memory, attention, motor/reaction times, and even creativity. Understanding the immediate effects of a single bout of exercise is the first step to understanding how the positive effects of exercise may accrue over time to cause long-lasting changes in select brain circuits. Researchers not only summarize the behavioral and cognitive effects of a single bout of exercise, but also summarize data from a large number of neurophysiological and neurochemical studies in both humans and animals showing the wide range of brain changes that result from a single session of physical exercise (i.e., acute exercise). 
According to principal investigator Wendy A. Suzuki, PhD, Professor of Neural Science and Psychology in the Center for Neural Science, New York University, "Exercise interventions are currently being used to help address everything from cognitive impairments in normal aging, minimal cognitive impairment (MCI), and Alzheimer's disease to motor deficits in Parkinson's disease and mood states in depression. Our review highlights the neural mechanisms and pathways by which exercise might produce these clinically relevant effects."
The investigators summarized a large and growing body of research examining the changes that occur at the cognitive/behavioral, neurophysiological, and neurochemical levels after a single bout of physical exercise in both humans and animals. They reviewed brain imaging and electrophysiological studies, including electroencephalography (EEG), functional magnetic resonance imaging (fMRI), functional near-infrared spectroscopy (fNIRS), and transcranial magnetic stimulation (TMS). They then turned to neurochemical studies, including lactate, glutamate and glutamine metabolism, effects on the hypothalamic-pituitary-adrenal (HPA) axis through cortisol secretion, and neurotrophins such as brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1), and vascular endothelial growth factor (VEGF). Neurotransmitter studies of monoamines (dopamine, serotonin, epinephrine and norepinephrine), acetylcholine, glutamate and gamma-aminobutyric acid (GABA) were reviewed, as well as neuromodulators such as endogenous opioids and endocannabinoids.
This extensive review resulted in three main observations. First, the most consistent behavioral effects of acute exercise are improved executive function, enhanced mood, and decreased stress levels. Second, neurophysiological and neurochemical changes that have been reported after acute exercise show that widespread brain areas and brain systems are activated. Third, one of the biggest open questions in this area is the relationship between the central neurochemical changes following acute exercise, that have mainly been described in rodents, and the behavioral changes seen after acute exercise reported in humans. Bridging this gap will be an important area of future study.
Co-author Julia C. Basso, PhD, post-doctoral research fellow, Center for Neural Science at New York University, commented, "The studies presented in this review clearly demonstrate that acute exercise has profound effects on brain chemistry and physiology, which has important implications for cognitive enhancements in healthy populations and symptom remediation in clinical populations."
Source: Brain Plasticity.

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Dementia with Lewy bodies, new international guidelines

ROCHESTER, Minn. -- Susan Williams, wife of the late actor and comedian Robin Williams, called Lewy body disease "the terrorist inside my husband's brain. An estimated 1.4 million Americans have dementia with Lewy bodies, making it the second-leading cause of dementia after Alzheimer's disease. A degenerative and ultimately fatal brain disease, dementia with Lewy bodies frequently is misdiagnosed as Alzheimer's or Parkinson's disease.
According to research reported online Wednesday, June 7, in Neurology, the international Dementia with Lewy Bodies Consortium issued new guidelines about diagnosing and treating the disease and called for more clinical trials into the illness.
"The updated clinical criteria and associated biomarkers hopefully will lead to earlier and more accurate diagnosis, and that is key to helping patients confront this challenging illness and maximize their quality of life," says Bradley Boeve, M.D., a co-author of the paper and a neurologist at Mayo Clinic, which sponsored an international dementia with Lewy bodies conference with roughly 400 clinicians, scientists, patients and care partners in Fort Lauderdale, Florida, in December 2015.
Yesterday's report is the first publication to come out of the conference. The previous consensus guidelines were published in 2005. By weighting clinical signs and biomarkers, the new recommendations give detailed guidance to help diagnose dementia with Lewy bodies. Its' symptoms include:
  • Cognitive problems: Confusion, reduced attention span and memory loss
  • Fluctuating attention: Drowsiness, staring into space, daytime naps and disorganized speech
  • Visual hallucinations: Seeing animals or people that aren't there.
  • Sleep difficulties: Physically acting out dreams while asleep and excessive daytime sleepiness
  • Movement disorders: Slowed movement, rigid muscles, tremors or shuffling walk
  • Poor regulations of body function: Dizziness, falls and bowel issues.
  • Depression: Persistent sadness and loss of interest
"Despite dementia with Lewy bodies being relatively common, some physicians and many in the public still have never heard of this disorder," Dr. Boeve says.
Protein deposits -- named after Frederick Lewy who discovered them -- develop in brain cells and are believed to cause some to die and others to malfunction. The new guidelines give treatment recommendations, such as using medications called cholinesterase inhibitors to try to improve cognition by triggering nerve impulses from one brain cell to the next.
"Previously, there has been little agreement on the optimal medication and non-medication approaches for patients and their families," Dr. Boeve notes.
###
The report has more than 60 contributors, worldwide experts in their field, including first author Ian McKeith, M.D., of Newcastle University in England and senior author Kenji Kosaka, M.D., of Yokohama City University Medical Center in Japan.
In addition to Dr. Boeve, Mayo Clinic co-authors are Dennis Dickson, M.D.; Tanis Ferman, Ph.D.; Neill Graff-Radford, M.D.; Kejal Kantarci, M.D.; Angela Lunde; Pamela McLean, Ph.D.; Melissa Murray, Ph.D.; and Owen Ross, Ph.D.
The National Institute on Aging and National Institute of Neurological Disorders and Stroke of the National Institutes of Health supported this work, among others. The authors noted conflict of interest disclosures.
About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to clinical practice, education and research, providing expert, whole-person care to everyone who needs healing. For more information, visit mayoclinic.org/about-mayo-clinic or newsnetwork.mayoclinic.org/.

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Blood biomarker for Huntington's disease

The first blood test that can predict the onset and progression of Huntington's disease has been identified by a UCL-led study. The researchers say their findings, published in Lancet Neurology, should help test new treatments for the genetic brain disorder, which is fatal and currently incurable. "This is the first time a potential blood biomarker has been identified to track Huntington's disease so strongly," said the study's senior author, Dr Edward Wild (UCL Institute of Neurology).
The test measures the neurofilament light chain (neurofilament), a protein released from damaged brain cells, which has been linked to other neurodegenerative diseases but hasn't been studied in the blood of Huntington's disease (HD) patients before.
The team, led by scientists at UCL Huntington's Disease Centre working with colleagues in Sweden, the USA, Canada, France and the Netherlands, measured neurofilament levels in blood samples from the TRACK-HD study, an international project that followed 366 volunteers for three years. They found that levels of the brain protein were increased throughout the course of HD -- even in carriers of the HD genetic mutation who were many years from showing symptoms of the disease. HD mutation carriers had neurofilament concentrations that were 2.6 times that of the control participants, and the level rose throughout the disease course from premanifest to stage 2 disease.
In the group who had no symptoms at the start of the study, the level of neurofilament predicted subsequent disease onset, as volunteers with high neurofilament levels in the blood at the start were more likely to develop symptoms in the following three years. After taking into account factors already known to predict progression -- age and a genetic marker -- the blood level of neurofilament was still able to independently predict onset, progression and the rate of brain shrinkage as measured by MRI scans.
Currently, the best biomarkers available are measured with neuroimaging or cerebrospinal fluid, which are more difficult and expensive to obtain than a blood test. The researchers say that predicting progression in mutation carriers who do not yet show symptoms has been particularly challenging.
"We have been trying to identify blood biomarkers to help track the progression of HD for well over a decade, and this is the best candidate that we have seen so far," said Dr Wild. "Neurofilament has the potential to serve as a speedometer in Huntington's disease, since a single blood test reflects how quickly the brain is changing. That could be very helpful right now as we are testing a new generation of so-called 'gene silencing' drugs that we hope will put the brakes on the condition. Measuring neurofilament levels could help us figure out whether those brakes are working."
The researchers caution that the test is not expected to be immediately helpful for individual patients. "This is the first time neurofilament has been measured in blood, so much more work is needed to understand the potential and limitations of this test," said Lauren Byrne (UCL Institute of Neurology), the study's first author. "In the future, if drugs to slow HD become available, it may well be used to guide treatment decisions. For now, this test is most promising as a much-needed tool to help us design and run clinical trials of new drugs."
Dr Robert Pacifici, chief scientific officer of CHDI Foundation, a US non-profit Huntington's disease research foundation, welcomed the development. "I can see neurofilament becoming a valuable tool to assess neuroprotection in clinical trials so that we can more quickly figure out whether new drugs are doing what we need them to. As a drug hunter, this is great news."
The study's funders included the CHDI foundation, GlaxoSmithKline, Swedish Research Council, European Research Council, Wallenberg Foundation and Wolfson Foundation.
About Huntington's disease:
Huntington's disease is a fatal genetic neurological disease. It usually develops in adulthood and causes abnormal involuntary movements, psychiatric symptoms and dementia. Approximately 10,000 people in the UK have HD with around 25,000 at risk. It is incurable, and no effective treatments exist to slow it down. Patients usually die within 20 years of the start of symptoms. HD is caused by a single known genetic mutation, and each child of a carrier of the mutation has a 50% chance of inheriting the disease.
Source: UNIVERSITY COLLEGE LONDON

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Child obesity linked to drinking diet beverages during pregnancy

Children born to women who had gestational diabetes and drank at least one artificially sweetened beverage per day during pregnancy were more likely to be overweight or obese at age 7, compared to children born to women who had gestational diabetes and drank water instead of artificially sweetened beverages, according to a study led by researchers at the National Institutes of Health. Childhood obesity is known to increase the risk for certain health problems later in life, such as diabetes, heart disease, stroke and some cancers. The study appears online in the International Journal of Epidemiology. 

According to the study authors, as the volume of amniotic fluid increases, pregnant women tend to increase their consumption of fluids. To avoid extra calories, many pregnant women replace sugar-sweetened soft drinks and juices with beverages containing artificial sweeteners. Citing prior research implicating artificially sweetened beverages in weight gain, the study authors sought to determine if diet beverage consumption during pregnancy could influence the weight of children. 

"Our findings suggest that artificially sweetened beverages during pregnancy are not likely to be any better at reducing the risk for later childhood obesity than sugar-sweetened beverages," said the study's senior author, Cuilin Zhang, Ph.D., in the Epidemiology Branch at NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). "Not surprisingly, we also observed that children born to women who drank water instead of sweetened beverages were less likely to be obese by age 7." 

The researchers analyzed data collected from 1996 to 2002 by the Danish National Birth Cohort, a long-term study of pregnancies among more than 91,000 women in Denmark. At the 25th week of pregnancy, the women completed a detailed questionnaire on the foods they ate. The study also collected data on the children's weight at birth and at 7 years old.

In the current study, the NICHD team limited their analysis to data from more than 900 pregnancies that were complicated by gestational diabetes, a type of diabetes that occurs only during pregnancy. Approximately 9 percent of these women reported consuming at least one artificially sweetened beverage each day. Their children were 60 percent more likely to have a high birth weight, compared to children born to women who never drank sweetened beverages. At age 7, children born to mothers who drank an artificially sweetened beverage daily were nearly twice as likely to be overweight or obese. Consuming a daily artificially sweetened beverage appeared to offer no advantages over consuming a daily sugar-sweetened beverage. At age 7, children born to both groups were equally likely to be overweight or obese. However, women who substituted water for sweetened beverages reduced their children's obesity risk at age 7 by 17 percent. It is not well understood why drinking artificially sweetened beverages compared to drinking water may increase obesity risk. 

The authors cited an animal study that associated weight gain with changes in the types of bacteria and other microbes in the digestive tract. Another animal study suggested that artificial sweeteners may increase the ability of the intestines to absorb the blood sugar glucose. Other researchers found evidence in rodents that, by stimulating taste receptors, artificial sweeteners desensitized the animals' digestive tracts, so that they felt less full after they ate and were more likely to overeat. The authors caution that more research is necessary to confirm and expand on their current findings. 

Although they could account for many other factors that might influence children's weight gain, such as breastfeeding, diet and physical activity levels, their study couldn't definitively prove that maternal artificially sweetened beverage consumption caused the children to gain weight. The authors mention specifically the need for studies that use more contemporary data, given recent upward trends in the consumption of artificially sweetened beverages. They also call for additional investigation on the effects of drinking artificially sweetened beverages among high-risk racial/ethnic groups.

Zhu, Y., et al. Maternal consumption of artificially sweetened beverages during pregnancy, and offspring growth through 7 years of age: a prospective cohort study. Int J Epidemiol. DOI: https://doi.org/10.1093/ije/dyx095 

 About the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): NICHD conducts and supports research in the United States and throughout the world on fetal, infant and child development; maternal, child and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit NICHD's website. 

 About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

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How neurons use crowd-sourcing to make decisions

SANTA FE INSTITUTE: How do we make decisions? Or rather, how do our neurons make decisions for us? Do individual neurons have a strong say or is the voice in the neural collective? One way to think about this question is to ask how many of my neurons you would have to observe to read my mind. If you can predict I am about to say the word "grandma" by watching one of my neurons then we could say our decisions can be attributed to single, perhaps "very vocal," neurons. In neuroscience such neurons are called "grandmother" neurons after it was proposed in the 1960's that there may be single neurons that uniquely respond to complex and important percepts like a grandmother's face.

On the other hand, if you can only read my mind by polling many of my neurons then it would appear the decision a collective one, distributed across hundreds, thousands, or even millions of neurons. A big debate in neuroscience is whether single-neuron encoding or distributed encoding is most relevant for understanding how the brain functions. 

In fact, both may be right. In research recently published in Frontiers in Neuroscience, Bryan Daniels, Jessica Flack, and David Krakauer of the Santa Fe Institute's collective computation group (C4) tackle this problem using data recorded from the neurons of a macaque monkey tasked by the experimenter with making a simple decision. 

In an area of the brain involved in the decision-making process, Daniels and colleagues find that as the monkey initially processes the data, polling many neurons is required to get a good prediction of the monkey's decision. Then, as the time for committing to a decision approaches, this pattern shifts. The neurons start to agree and eventually each one on its own is maximally predictive. Hence at first the "neural voice" is heterogeneous and collective, but as the neurons get close to the decision point, the "neural voice" becomes homogenous and, in a sense, individualistic, as any neuron on its own is sufficient to read the monkey's mind. 

Daniels says a possible explanation for this odd behavior is that the system has two tasks to solve. It must gather good information from noisy data and it must use this information to produce a coherent decision. To find regularities in the input it polls many individual neurons, as the crowd's answer is more reliable than any single neuron's when the data are noisy. But, as Krakauer says, ultimately a decision has to be made. The neurons agree on an answer by sharing their information to come to a consensus. This explanation echoes results in other collective systems, from animal societies to systems studied in statistical physics. Flack says this commonality suggests a general principle of collective computation: It has two phases -- an information accumulation phase that uses crowdsourcing to collect reliable information and a consensus phase that allows the system to act.

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Microglia May Be Involved in Alzheimer's, Parkinson's, Huntington's, Schizophrenia, Autism and Depression

Scientists have, for the first time, characterized the molecular markers that make the brain's front lines of immune defense--cells called microglia--unique. In the process, they discovered further evidence that microglia may play roles in a variety of neurodegenerative and psychiatric illnesses, including Alzheimer's, Parkinson's and Huntington's diseases as well as schizophrenia, autism and depression.

"Microglia are the immune cells of the brain, but how they function in the human brain is not well understood," says Rusty Gage, professor in Salk's Laboratory of Genetics, the Vi and John Adler Chair for Research on Age-Related Neurodegenerative Disease, and a senior author of the new work. "Our work not only provides links to diseases but offers a jumping off point to better understand the basic biology of these cells."

Genes that have previously been linked to neurological diseases are turned on at higher levels in microglia compared to other brain cells, the team reported in Science on May 25, 2017. While the link between microglia and a number of disorders has been explored in the past, the new study offers a molecular basis for this connection.

"These studies represent the first systematic effort to molecularly decode microglia," says Christopher Glass, a Professor of Cellular and Molecular Medicine and Professor of Medicine at University of California San Diego, also senior author of the paper. "Our findings provide the foundations for understanding the underlying mechanisms that determine beneficial or pathological functions of these cells."

Microglia are a type of macrophage, white blood cells found throughout the body that can destroy pathogens or other foreign materials. They're known to be highly responsive to their surroundings and respond to changes in the brain by releasing pro-inflammatory or anti-inflammatory signals. They also prune back the connections between neurons when cells are damaged or diseased. But microglia are notoriously hard to study. They can't be easily grown in a culture dish and quickly die outside of a living brain.

Nicole Coufal, a pediatric critical care doctor at UC San Diego, who also works in the Gage lab at Salk, wanted to make microglia from stem cells. But she realized there wasn't any way to identify whether the resulting cells were truly microglia.

"There was not a unique marker that differentiated microglia from circulating macrophages in the rest of the body," she says.

David Gosselin and Dylan Skola in the Glass lab, together with Coufal and their collaborators, set out to characterize the molecular characteristics of microglia. They worked with neurosurgeons at UC San Diego to collect brain tissue from 19 patients, all of who were having brain surgery for epilepsy, a brain tumor or a stroke. They isolated microglia from areas of tissue that were unaffected by disease, as well as from mouse brains, and then set out to study the cells. The work was made possible by a multidisciplinary collaboration between bench scientists, bioinformaticians and clinicians.

The team used a variety of molecular and biochemical tests--performed within hours of the cells being collected--to characterize which genes are turned on and off in microglia, how the DNA is marked up by regulatory molecules, and how these patterns change when the cells are cultured.

Microglia, they found, have hundreds of genes that are more highly expressed than other types of macrophages, as well as distinct patterns of gene expression compared to other types of brain cells. After the cells were cultured, however, the gene patterns of the microglia began to change. Within just six hours, more than 2,000 genes had their expression turned down by at least fourfold. The results underscore how dependent microglia are on their surroundings in the brain, and why researchers have struggled to culture them.

Next, the researchers analyzed whether any of the genes that were upregulated in microglia compared to other cells had been previously implicated in disease. Genes linked to a variety of neurodegenerative and psychiatric diseases, they found, were highly expressed in microglia.

"A really high proportion of genes linked to multiple sclerosis, Parkinson's and schizophrenia are much more highly expressed in microglia than the rest of the brain," says Coufal. "That suggests there's some kind of link between microglia and the diseases."

For Alzheimer's, more than half of the genes known to affect a person's risk of developing the disease were expressed more highly in microglia than other brain cells.

In mice, however, many of the disease genes weren't as highly expressed in microglia. "That tells us that maybe mice aren't the best model organisms for some of these diseases," Coufal says.

More work is needed to understand exactly how microglia may be altered in people with diseases, but the new molecular profile of microglia offers a way for researchers to begin trying to better culture the cells, or coax stem cells to develop into microglia for future studies.

Other researchers on the study were Baptiste Jaeger, Carolyn O'Connor, Conor Fitzpatrick, Monique Pena, and Amy Adair of the Salk Institute; Inge Holtman, Johannes Schlachetzki, Eniko Sajti, Martina Pasillas, David Gona, and Michael Levy of the University of California San Diego; and Richard Ransohoff of Biogen.

The work and the researchers involved were supported by grants from the Larry L. Hillblom Foundation, National Institutes of Health, Canadian Institute of Health Research, Multiple Sclerosis Society of Canada, University of California San Diego, Dutch MS Research Foundation, the Gemmy and Mibeth Tichelaar Foundation, the DFG, the JPB Foundation, Dolby Family Ventures, The Paul G. Allen Family Foundation, the Engman Foundation, the Ben and Wanda Hildyard Chair in Hereditary Diseases.

About the Salk Institute for Biological Studies:

Every cure has a starting point. The Salk Institute embodies Jonas Salk's mission to dare to make dreams into reality. Its internationally renowned and award-winning scientists explore the very foundations of life, seeking new understandings in neuroscience, genetics, immunology, plant biology and more. The Institute is an independent nonprofit organization and architectural landmark: small by choice, intimate by nature and fearless in the face of any challenge. Be it cancer or Alzheimer's, aging or diabetes, Salk is where cures begin. Learn more at: salk.edu.



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Brain Ages Fast With Less Sleep

Researchers at Duke-NUS Graduate Medical School Singapore (Duke-NUS) have found evidence that the less older adults sleep, the faster their brains age. These findings, relevant in the context of Singapore's rapidly ageing society, pave the way for future work on sleep loss and its contribution to cognitive decline, including dementia.

Past research has examined the impact of sleep duration on cognitive functions in older adults. Though faster brain ventricle enlargement is a marker for cognitive decline and the development of neurodegenerative diseases such as Alzheimer's, the effects of sleep on this marker have never been measured.

The Duke-NUS study examined the data of 66 older Chinese adults, from the Singapore-Longitudinal Aging Brain Study(1). Participants underwent structural MRI brain scans measuring brain volume and neuropsychological assessments testing cognitive function every two years. Additionally, their sleep duration was recorded through a questionnaire. Those who slept fewer hours showed evidence of faster ventricle enlargement and decline in cognitive performance.

"Our findings relate short sleep to a marker of brain aging," said Dr June Lo, the lead author and a Duke-NUS Research Fellow. "Work done elsewhere suggests that seven hours a day(2) for adults seems to be the sweet spot for optimal performance on computer based cognitive tests. In coming years we hope to determine what's good for cardio-metabolic and long term brain health too," added Professor Michael Chee, senior author and Director of the Centre for Cognitive Neuroscience at Duke-NUS.

1) The Singapore-Longitudinal Aging Brain Study (started in 2005) follows a cohort of healthy adults of Chinese ethnicity aged 55 years and above. This study is one of the few in Asia that tracks the brain structures and cognitive functions of older adults so closely.

2) Data collected by Lumosity, an online brain-training program, suggests that self-reported sleep duration of seven hours is associated with the best cognitive test scores in over 150,000 adults. As of now it is unknown if this amount of sleep is optimum for cardio metabolic and long-term brain health.


June C. Lo, Kep Kee Loh, Hui Zheng, Sam K.Y. Sim, Michael W.L. Chee. Sleep Duration and Age-Related Changes in Brain Structure and Cognitive PerformanceSLEEP, 2014; DOI: 10.5665/sleep.3832

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