Learning to ‘talk things through in your head’ may help autistic people


Teaching children with autism to ‘talk things through in their head’ may help them to solve complex day-to-day tasks, which could increase the chances of independent, flexible living later in life, according to new research.

The study, led by Durham University, found that the mechanism for using ‘inner speech’ or ‘talking things through in their head’ is intact in children with autism but not always used in the same way as typically developing children do.

The psychologists found that the use, or lack of, thinking in words is strongly linked to the extent of someone’s communication impairments which are rooted in early childhood.

However, the researchers suggest teaching and intervention strategies for children targeted at encouraging inner speech may make a difference. These strategies, which include encouraging children to describe their actions out loud, have already proven useful for increasing mental flexibility among typically developing children.

It is also suggested that children with autism ) could, for example, benefit from verbal learning of their daily schedule at school rather than using visual timetables as is currently a common approach.

The research by Durham University, Bristol University and City University London is published in Development and Psychopathology.

Lead author, Dr David Williams, lecturer in the Department of Psychology at Durham University, said: “Most people will ‘think in words’ when trying to solve problems, which helps with planning or particularly complicated tasks. Young typically developing children tend to talk out loud to guide themselves when they face challenging tasks.

“However, only from about the age of seven do they talk to themselves in their head and, thus, think in words for problem-solving. How good people are at this skill is in part determined by their communication experiences as a young child.”

One out of every 100 people in the UK has Aautism D, which is diagnosed on the basis of a set of core impairments in social engagement, communication and behavioural flexibility. Children with autism often miss out on the early communicative exchanges when they are young which may explain their tendency not to use inner speech when they are older. This relative lack of inner speech use might contribute to some of the repetitive behaviours which are common in people with autism.

In the study, those individuals with more profound communication impairments also struggled most with the use of inner speech for complex tasks. People with ASD did, however, use inner speech to recall things from their short-term memory.

Dr Williams said: “These results show that inner speech has its roots in interpersonal communication with others early in life, and it demonstrates that people who are poor at communicating with others will generally be poor at communicating with themselves.

“It also shows that there is a critical distinction between being able to express yourself verbally and actually using silent language for problem-solving. For example, the participants with autism in our study were verbally able, yet did not use inner speech to support their planning.”

Caroline Hattersley, Head of Information, Advice and Advocacy at the National Autistic Society, said: “This study presents some interesting results and could further our understanding of autism. If the findings are replicated on a wider scale they could have a significant impact on how we develop strategies to support children with the disability.”

METHODS

In the study, 15 high-functioning adults with autism and 16 comparison participants were asked to complete a commonly used task which measures planning ability, called the Tower of London task. This task consists of five coloured disks that can be arranged on three individual pegs. The aim of the task is to transform one arrangement of disks into another by moving the disks between the pegs, one disk at a time, in as few moves as possible. This type of complex planning task is helped by ‘talking to yourself in your head’.

The participants did the task under normal conditions as well as under an ‘articulatory suppression’ condition whereby they had to repeat out loud a certain word throughout the task – in this case, either the word ‘Tuesday’ or ‘Thursday’. If someone uses inner speech to help them plan, articulatory suppression prevents them from doing so and will detrimentally affect their planning performance, whereas it will have little impact on the planning performance of someone who doesn’t use inner speech.

The results showed that whilst almost 90 per cent of normally developing adults did significantly worse on the Tower of London task when asked to repeat the word, only a third of people with autism were in any way negatively affected by articulatory suppression during the task. This suggests that, unlike neurotypical adults, participants with autism do not normally use inner speech to help themselves plan.

The participants also completed a short-term memory task to asses the use of inner speech in short-term recall.

CASE STUDY

Jude Ragan OBE is Headteacher at Queensmill School in London. Queensmill School is one of the largest state funded schools for children with autism which has over 100 pupils and is accredited by the National Autistic Society.

Jude Ragan OBE said: “Complex planning ahead is not a strength of people with autism which means, for people most severely affected, that they can only comprehend the here and now. This can be hugely stressful and at times quite frightening. Everything that we do in an ASD specific school is to help our pupils recognise when something they are doing might finish, what might happen next and so on. Encouraging inner speech is very much part of that as it can work as a life-long support.

“In order to encourage children to use inner speech, we start with visual timetables when they are in nursery. This will have pictures for different activities, such as a nappy for toilet time and a spoon for lunch. We will change this as the child progresses, to symbols, then symbols with words and then words only. By the time we are using written tick lists for the child to know what they are doing when, this will be accompanied by speech to begin to build the foundations for inner speech to solve problems.

“We can then ask the child questions such as ‘What do you have next Tim? What will you need for that? Which room is it in? What happens after that? This is all scaffolding for inner speech which is naturally a more ‘normal’ way of planning and one that we would want a child to move to if they have the ability to do so.

“We also use ‘parallel talk’ whereby we play alongside the child and talk through what he or she is doing. That way, we are teaching them in a playful way to talk things through. We know that neurotypical children learn a great deal about how the world and social interaction works by naturally talking whilst they are playing but children with autism do not normally do this. It is important for us to show them how they can do that.

“Peer-reviewed research like this is very valuable as it informs the way we teach our pupils. As educators, we need to remind ourselves that whilst responding to visual cues is a strength of autism, we should never miss an opportunity to develop language, particularly inner language which I feel is more comfortable to a person with autism than spoken language.”

Placenta may hold clues for early autism diagnosis and intervention

Loss of placental hormone linked to brain and social behavior changes


New UC Davis MIND Institute research has identified a novel human gene linked to fetal brain development and autism . The discovery also links the gene to the mother’s early prenatal vitamin use and placental oxygen levels.

In a study published Feb. 16 in Genome Biology, the researchers used genomic sequencing to find a DNA methylation signature in the placenta of newborns eventually diagnosed with autism. This signature mark was linked to early fetal neurodevelopment.

“By taking an unbiased approach to investigating placental DNA methylation differences, we discovered a novel gene in a poorly mapped region of the genome associated with autism, ” said Janine LaSalle, lead author on the study and professor of microbiology and immunology at UC Davis Health.

Autism is a complex neurological condition linked to genetic and environmental factors. The U.S. Centers for Disease Control and Prevention (CDC) estimates that one in 44 children are diagnosed with autism. It is much more prevalent in males than females.

Why studying the placenta is important

The placenta supports fetal development in the uterus. It regulates oxygen supply and metabolism and provides hormones and neurotransmitters critical for the fetus’ developing brain.

“The placenta is an often misunderstood and overlooked tissue, despite its importance in regulating and thereby reflecting events critical to brain development in utero. It is like a time capsule for finding things that happened in utero. For decades, hospital births have thrown away placentae despite this tissue being a gold mine for finding molecular clues to child outcomes,” LaSalle said.

During pregnancy, the fetus might experience oxidative stress, an imbalance of free radicals and antioxidants in the body. This is common in normal brain development. However, in some cases, exposure to environmental factors such as air pollution and pesticides can lead to excessive oxidative stress. This state can lead to cell and tissue damage or delayed neurodevelopment.

“Oxidative stress is normal.  But excessive oxidative stress may come from environmental exposures linked to autismsuch as air pollution, pesticides, maternal obesity and inflammation,” LaSalle said.

The epigenome is a set of chemical compounds and proteins that tell the DNA what to do. These compounds attach to DNA and modify its function. One such compound is CH3 (known as the methyl group) which leads to DNA methylation. The neonatal epigenome can reflect past interactions between genetic and environmental factors during early development. It may also influence future health outcomes.

The placenta is a promising tissue for identifying DNA methylation changes at genes that also function in the fetal brain. This study examined the association of autism with placental DNA methylation.

Finding factors in mother’s placenta that might predict autism

The researchers studied the development of 204 children born to mothers enrolled in the MARBLES and EARLI studies. These mothers had at least one older child with autism and were considered with higher probability of having another child with autism m. When these children were born, the mothers’ placentae were preserved for future analysis.

At 36 months, the children got diagnostic and developmental assessments. Based on these tests, the researchers grouped the children under “typically developing” (TD), “with autism ” and “non-typical development” (Non-TD).

The researchers also extracted and quantified the DNA from the placenta tissues. They divided the placenta samples into discovery, replication and specificity replication groups.

For the discovery group, they split and sequenced 92 samples (46 ASD, 46 TD) from the MARBLES study using whole-genome bisulfite sequencing (WGBS) and whole-genome sequencing (WGS). To determine if differential methylation was reproducible in a different population, the replication group included WGBS data from 16 ASD and 31 TD samples from the EARLI study.

The specificity replication group had 21 autism , 13 Non-TD and 31 TD placenta samples from the MARBLES study. The researchers used these samples to determine if methylation changes were specific to autism .

Finally, they performed whole genome sequencing on 41 ASD and 37 TD MARBLES children.

Placenta to reveal insights into genes related to autism

The researchers identified a block of differential methylation in autism at 22q13.33, a region in chromosome 22 not previously linked to autisk . They located and characterized a novel gene known as LOC105373085 within that region and renamed it NHIP (neuronal hypoxia inducible, placenta associated).

To understand the function of this gene, they detected the levels of NHIP expression in human cell lines and brain tissue. They tested the responsiveness of NHIP to hypoxia, a state of low oxygen levels in the tissues. The researchers found that NHIP is a gene that gets turned on in neurons following hypoxia and regulates other gene pathways with functions in neuronal development and response to oxidative stress.  Higher NHIP levels increased the cell division in an embryonic cell line.

This is important because in the placenta, hypoxia triggers placental cell division to make further contact with maternal blood vessels to supply enough oxygen for the developing brain.

“We found that the NHIP gene is active in the brain, responsive to oxidative stress, and influences expression of other known genes associated with autism,” LaSalle said. “In most pregnancies, the placenta experiences some inevitable levels of stress. We think that NHIP is there to buffer the effects of excessive oxidative stress.”

Prenatal vitamins and autism

Another remarkable finding from the study was the role prenatal vitamins play in regulating the work of NHIP. Prenatal vitamins are high in folic acid and can reduce oxidative stress.

Prenatal vitamins use during the first month of pregnancy showed a significant protective effect among individuals with genetic differences at 22q13.33 NHIP region. Taking prenatal vitamins in the first month of pregnancy seems to provide essential metabolic elements to counteract the genetic inheritance of reduced NHIP responsiveness to oxidative stress.

“In line with previous studies, we found that taking a prenatal vitamin is essential when planning a pregnancy,” said LaSalle. “Findings from our study provide key insights that may help in identifying newborns more likely to develop autism and getting them into an earlier intervention or just knowing to watch them sooner.”

 The researchers pointed out that these results will require further replication before being used diagnostically.

Diet & Multiple Sclerosis: Swank vs Wahls Study

Swank Vs. Wahls Randomized Trial for Multiple Sclerosis [Analysis of the  WAVES Study] - YouTube


MStranslate co-founder and chief science communicator, Brett Drummond, explores a recent study comparing two popular diet protocols for people living with multiple sclerosis – the Swank Protocol and the Wahls Protocol. This research was conducted by investigators at the University of Iowa and funded by the National Multiple Sclerosis Society.

Anti-cell death agent a potential treatment for vision loss associated with Multiple Sclerosis

Optic Neuritis in MS Mouse


This image shows myelin (blue) in the optic nerve of a normal mouse (top), a mouse with optic neuritis (middle), and an optic neuritis mouse treated with ST266 (bottom) .Ken Shindler, MD, PhD, Perelman School of Medicine, University of Pennsylvania

 A new therapeutic agent tested in a mouse model of multiple sclerosis (MS) produced anti-inflammatory activity and prevented loss of cells in the optic nerve, according to a new study by researchers in the Perelman School of Medicine at the University of Pennsylvania, with Pittsburgh-based Noveome Biotherapeutics. The research was conducted in the laboratory of Kenneth Shindler, MD, PhD, an associate professor of Ophthalmology and Neurology, and published in Scientific Reports.

The team demonstrated the therapeutic potential of the agent, called ST266, for treating optic neuritis, inflammation that damages the optic nerve and is a common presenting feature of MS. About half of patients diagnosed with MS experience optic neuritis, which can cause mild to moderate permanent loss of vision, but rarely complete blindness. ST266 is a solution of molecules that stimulate paracrine signaling. This is one way in which cells “talk” to each other: One cell produces a chemical signal that induces changes in nearby cells.

“In this case, the idea is that the many factors in ST266 not only bind to cell receptors and cause changes within the cells they bind to, but those cells then alter their own secretions and provide additional signals to other neighboring cells, thus propagating an effect from a relatively small amount of protein present in the therapy itself,” Shindler said. “To the best of our knowledge, this study demonstrates, for the first time, the ability to treat the optic nerve via the intranasal route of administration.”

When ST266 was given to the MS mice via their nose, it reached the central nervous system within 30 minutes and was detected at higher concentrations in parts of the eye and optic nerve compared to other areas of the brain. These findings demonstrated that this type of delivery can target tissues of the eye, which is easier, less painful, and less invasive than injecting medication directly into the eye.

In mice with optic neuritis, the team showed that early treatment with ST266 prevented damage and dysfunction, marked by significantly reduced loss of optic nerve cells, and suppression of inflammatory cell infiltration into the optic nerve. This in turn was associated with limitation of the degree of demyelination caused by MS- related optic neuritis. However, “it’s not known if these effects are independent effects of the therapy or interdependent effects,” Shindler said.

Treatment of later-stage optic neuritis in the MS mice showed similar results, resulting in improved visual function compared to untreated groups. The data suggest that ST266 helps promote optic neuron survival by potentially activating multiple pathways, including those that prevent cell death.

“These results are particularly important as the preservation of retinal cells is a significant factor when treating optic neuritis,” Shindler said. “There is an increased need for combination treatment options that are able to prevent nerve-cell axon loss for patients with optic neuritis.”

Currently, the only acute treatment for MS-related optic neuritis is IV steroids, which only hasten whatever amount of visual recovery will occur even without treatment. Steroids do not prevent nerve damage or permanent vision loss. “ST266’s ability to preserve vision in the preclinical model and reduce neuronal loss would be a huge advance if it translates to human patients,” Shindler said.

The study also has implications beyond MS-related optic problems. “We also showed an effect on cultured neurons, suggesting that effects may translate to other optic nerve diseases, as well as other brain neurodegenerative diseases,” Shindler said.

Your microbiome shapes your life. But where did it come from?

Microbiome Acquisition


Artist’s concept of this research that probes the odds of a new species being acquired by a microbiome ecosystem created by Navid Marvi, courtesy of the Carnegie Institution for Science. CREDIT By Navid Marvi, courtesy of the Carnegie Institution for Science.

The gut microbiome is an ecosystem of hundreds to thousands of microbial species living within the human body. These populations affect our health, fertility, and even our longevity. But how do they get there in the first place?

New collaborative work led by Carnegie’s William Ludington reveals crucial details about how the bacterial communities that comprise each of our individual gut microbiomes are acquired. These findings, published in the Proceedings of the National Academy of Sciences, have major implications for treatments such as fecal transplants and probiotic administration.

“There is a huge amount of variation in microbiome composition between individuals,” Ludington explained. “For example, if you look at the sum total of all of the bacterial species that are adapted to live in the gastrointestinal systems of humans, most of these are not present in a majority of people. That’s how incredibly diverse these gut microbial populations are.”

A combination of elements, including genetics, diet, and environment contribute to the differences between our microbiomes. But there isn’t a direct line between these inputs and the species that successfully colonize our guts. There’s an element of chance at play each time we are exposed to a new microbe as to whether it will be acquired and become a member of our gut ecosystem. Ludington and his collaborators set out to understand the factors that shape the odds of this colonization process.

Although many researchers have studied microbiome compositions in natural populations, there have been few attempts to use a controlled environment to reveal the process by which new species successfully join the gut microbial ecosystem. Ludington and his collaborators—Eric Jones and David Sivak of Simon Fraser University and Jean Carlson of UC Santa Barbara—developed a new ecological model to understand how we acquire the specific mix of microbes that are individual to our own particular gut communities.  

Working in the comparatively much less complicated microbiomes of fruit flies, the team showed that exposure to a microbial species does not guarantee its successful incorporation into the microbiome ecosystem. They found that the state of the microbiome, and interactions between existing microbiome member species, sets the odds for whether a newly encountered bacteria is added into the mix.

“Even among genetically identical flies that lived in the same housing and were fed the same diets, we saw variations in microbiome composition,” Sivak said.

The researchers then used these results to build mathematical models that could probe increasingly complex scenarios by which new microbiome species could be acquired, leading to their breakthrough understanding of the community factors that shape membership in the microbiome ecosystem.

“Think of microbiome composition as a big party where the social dynamics determine who leaves early and who stays until dawn,” said Ludington.

Added Jones, the paper’s first author: “Bacterial colonization depends on a number of complicated factors that we’re just starting to understand.  We showed, for example, that some groups of species facilitate each other’s colonization and are therefore more likely to coexist.”

These group interactions have exciting implications for how microbiomes are transmitted between individuals, including how medical professionals might drive a person’s microbiome towards a desired composition.

“The beauty of the mathematical approach we deployed is that it acknowledges that colonization is a roll of the dice, but we are now able to attribute the weighting of the dice to biological interactions with a molecular basis that has been honed by evolution,” said Carlson.

The team’s findings provide a framework for quantitatively examining the mechanisms that therapies such as fecal transplants and probiotics depend upon, advancing toward the eventual goal of personalized microbiome medicine.