1. Study identifies biomarker for atypical development in infants at risk for developing autism

    September 24, 2017 by Ashley

    From the Columbia University Medical Center press release:

    New research from the Sackler Institute for Developmental Psychobiology at Columbia University Medical Center (CUMC) identifies a potential biomarker that predicts atypical development in 1- to 2-month-old infants at high versus low familial risk for developing autism spectrum disorders (ASD). The search for neurobiological markers that precede atypical trajectories is important in infants with a high risk for developing autism-related disorders because early recognition allows for early intervention and mitigation of difficulties later in life.

    Using data from National Database for Autism Research (NDAR), lead author Kristina Denisova, PhD, Assistant Professor of Psychiatry at CUMC and Fellow at the Sackler Institute, studied 71 high and low risk infants who underwent two functional Magnetic Resonance imaging brain scans either at 1-2 months or at 9-10 months: one during a resting period of sleep and a second while native language was presented to the infants. After extracting measures of head movements during the scans, the statistical characteristics of these movements were quantified.

    The study found that infants at high risk for developing ASD have elevated levels of “noise” and increased randomness in their spontaneous head movements during sleep, a pattern possibly suggestive of problems with sleep. In addition, 1- to 2-month-old high risk infants showed more similar signatures while listening to native language and while sleeping while low risk infants showed distinct signatures during the two conditions.

    Further, specific features of head movements during sleep at 1-2 months predicted future flatter (delayed) early learning developmental trajectories in the high-risk babies. The existence of generally atypical learning trajectories in the high risk group was verified in separate data sets from four representative high risk infant-sibling studies comprising a total of 1,445 infants with known ASD outcomes as children. These analyses showed that high risk infants — even those without ASD diagnoses — have significantly lower functioning in childhood relative to low risk infants. The current study reveals a possible way to predict which 1-2 months-old infants will show atypical developmental trajectories as toddlers.

    Dr. Denisova said, “The finding that head movement signatures are responsive to high context stimuli (native language speech) in low but not high risk infants is informative because it suggests that infants whose siblings were diagnosed with ASD are less attuned to evolutionarily important stimuli early in life.” She added that this response pattern may underlie atypical information processing in individuals with neurodevelopmental disorders.

    Dr. Jeremy Veenstra-VanderWeele, MD, an autism researcher who was not involved in this study, noted, “This study is a good example of how existing data can be mined for new insights. Additional work is needed to replicate the current findings and understand the underlying mechanisms, but this work suggests new ways to look at movement or motor function in infants at high risk of ASD.”


  2. Using DNA to predict schizophrenia, autism

    September 15, 2017 by Ashley

    From the Osaka University press release:

    Osaka University researchers show in a multi-institute collaboration that a single amino acid substitution in the protein CX3CR1 may act as predictor for schizophrenia and autism.

    Huntington’s disease, cystic fibrosis, and muscular dystrophy are all diseases that can be traced to a single mutation. Diagnosis in asymptomatic patient for these diseases is relatively easy — You have the mutation? Then you are at risk. Complex diseases, on the other hand, do not have a clear mutational footprint. A new multi-institutional study by Japanese researchers shows a potential rare gene mutation that could act as a predictor for two neurodevelopmental disorders, schizophrenia and autism.

    “Aberrant synapse formation is important in the pathogenesis of schizophrenia and autism,” says Osaka University Professor Toshihide Yamashita, one of the authors of the study. “Microglia contribute to the structure and function of synapse connectivities.”

    Microglia are the only cells in the brain that express the receptor CX3CR1. Mutations in this receptor are known to affect synapse connectivity and cause abnormal social behavior in mice. They have also been associated with neuroinflammatory diseases such as multiple sclerosis, but no study has shown a role in neurodevelopment disorders.

    Working with this hypothesis, the researchers conducted a statistical analysis of the CX3CR1 gene in over 7000 schizophrenia and autism patients and healthy subjects, finding one mutant candidate, a single amino acid switch from alanine to threonine, as a candidate marker for prediction.

    “Rare variants alter gene function but occur at low frequency in a population. They are of high interest for the study of complex diseases that have no clear mutational cause,” said Yamashita, who added the alanine threonine substitution was a rare variant.

    The structure of CX3CR1 includes a domain known as Helix 8, which is important for initiating a signaling cascade. Computer models showed that one amino acid change is enough to compromise the signaling.

    “The variant changes the region from hydrophobic to hydrophilic and destabilize Helix 8. We overexpressed the mutation in cells and found Akt signaling was disrupted,” explains Yamashita.

    According to Yamashita, the findings are the first to connect a genetic variation in microglia with neurodevelopment disorders. Moreover, he hopes that the discovery could become a basis for predictive diagnostics.

    “There is no reliable way to diagnose schizophrenia or autism in asymptomatic patients. Deeper understanding of the genetic risk factors will help us develop preventative measures.”


  3. Origins of autism: Abnormalities in sensory processing at six months

    September 13, 2017 by Ashley

    From the McGill University press release:

    The origins of autism remain mysterious. What areas of the brain are involved, and when do the first signs appear? New findings published in Biological Psychiatry brings us closer to understanding the pathology of autism, and the point at which it begins to take shape in the human brain. Such knowledge will allow earlier interventions in the future and better outcomes for autistic children.

    Scientists used a type of magnetic resonance imaging (MRI), known as diffusion weighted imaging, to measure the brain connectivity in 260 infants at the ages of 6 and 12 months, who had either high or low risks of autism. The lengths and strengths of the connections between brain regions was used to estimate the network efficiency, a measure of how well each region is connected to other regions. A previous study with 24-month-old children found that network efficiency in autistic children was lower in regions of the brain involved in language and other behaviours related to autism. The goal of this new study was to establish how early these abnormalities occur.

    Lead author John Lewis, a researcher at the Montreal Neurological Institute and Hospital of McGill University and the Ludmer Centre for Bioinformatics and Mental Health, found network inefficiencies had already been established in six-month-old infants who went on to be diagnosed with autism. Inefficiencies in the six-month-olds appeared in the auditory cortex. He also found the extent of the inefficiency at six months of age was positively related to the severity of autistic symptoms at 24 months. As the children aged, areas involved in processing of vision and touch, as well as a larger set of areas involved in sound and language, also showed such a relation between inefficiency and symptom severity.

    Identifying the earliest signs of autism is important because it may allow for diagnosis before behavioural changes appear, leading to earlier intervention and better prospects for a positive outcome. By pinpointing the brain regions involved in processing sensory inputs as the earliest known locations of neural dysfunction related to autism, researchers narrow down the genetic factors and mechanisms that could be responsible for its development. The fact that neurological signs are already present at six months also eliminates some environmental factors as potential causes of the disorder.

    “Our goal was to discover when and where in the brain the network inefficiencies first appeared,” says Lewis. “The results indicate that there are differences in the brains of infants who go on to develop autism spectrum disorder even at six months of age, and that those early differences are found in areas involved in processing sensory inputs, not areas involved in higher cognitive functions. We hope that these findings will prove useful in understanding the causal mechanisms in autism spectrum disorder, and in developing effective interventions.”

    The research comes from the Infant Brain Imaging Study (IBIS), a collaborative effort by investigators at the Montreal Neurological Institute, and four clinical sites in the United States, coordinated to conduct a longitudinal brain imaging and behavioural study of infants at high risk for autism.


  4. Altered mitochondria associated with increased autism risk

    September 7, 2017 by Ashley

    From the Children’s Hospital of Philadelphia press release:

    Mitochondria, the tiny structures inside our cells that generate energy, may play a key role in autism spectrum disorders (ASD). A provocative new study by Children’s Hospital of Philadelphia (CHOP)’s pioneering mitochondrial medicine team suggests that variations in mitochondrial DNA (mtDNA) originating during ancient human migrations may play an important role in predisposition to ASDs.

    “Our findings show that differences in mitochondrial function are important in ASD,” said study leader Douglas C. Wallace, PhD, director of the Center for Mitochondrial and Epigenomic Medicine at CHOP. “Our team demonstrates that a person’s vulnerability to ASD varies according to their ancient mitochondrial lineage.”

    Wallace and colleagues, including Dimitra Chalkia, Larry Singh and others, published their findings in JAMA Psychiatry.

    The scientists conducted a cohort study of genetic data from 1,624 patients and 2,417 healthy parents and siblings, representing 933 families in the Autism Genetic Resource Exchange (AGRE). The Center for Applied Genomics at CHOP had previously performed genome-wide association studies on this AGRE cohort, and partnered in this study.

    Mitochondria contain their own DNA, distinct from the more familiar nuclear DNA (nDNA) inside the cell nucleus. The mtDNA codes for essential genes governing cellular energy production, and those genes exchange biological signals with nDNA to affect our physiology and overall health.

    The current study analyzed single-nucleotide functional variants — base changes in the cohort’s mtDNA that characterize mitochondrial haplogroups. Haplogroups are lineages of associated mtDNA variants that reflect the ancient migration patterns of early human bands that spread out of Africa to the rest of the world during prehistory. Based on his seminal 1980 discovery that the human mtDNA is inherited only through the mother, Wallace’s surveys over the years, covering mtDNA variation among indigenous populations around the world, have permitted the reconstruction of human worldwide migrations and evolution patterns over hundreds of millennia.

    The current study found that individuals with European haplogroups designated I, J, K, X, T and U (representing 55 percent of the total European population) had significantly higher risks of ASD compared to the most common European haplogroup, HHV. Asian and Native American haplogroups A and M also were at increased risk of ASD.

    These mitochondrial haplogroups originated in different global geographic areas, adapted through evolution to specific regional environments. However, subsequent changes, such as migration, changes in diet, and other environmental influences, can create a mismatch between the physiology of a particular mtDNA lineage and the individual’s environment, resulting in predisposition to disease. Additional nDNA genetic factors or environmental insults may further reduce an individual’s energy output until it is insufficient to sustain normal brain development and function, resulting in disease.

    As the wiring diagram for cellular power plants, mtDNA is crucial in supplying energy to the body. The brain is particularly vulnerable to even mild energy deficiencies because of its high mitochondrial energy demand. Wallace’s previous studies have shown that mitochondrial dysfunction can disturb the delicate balance between inhibition and excitation in brain activity — a crucial factor in ASDs and other neuropsychiatric disorders. “There may be a bioenergetic threshold,” says Wallace, adding that an individual already predisposed to ASD based on their mitochondrial haplogroup may be pushed below that threshold by the chance occurrence of additional genetic variants or environmental insults.

    The striking tendency for ASD to occur more frequently in males than females may reflect another peculiarity of mitochondrial genetics, added Wallace. Males are four times more likely to suffer blindness from a well-known mtDNA disease, Leber hereditary optic neuropathy (LHON). The lower risk of blindness in females may arise from estrogen effects in mitochondria that increase beneficial antioxidant activity.

    Wallace said that his team’s finding that subtle changes in mitochondrial energetics are important risk factors in ASD suggests potential alternative approaches for therapy. He added, “There is increasing interest in developing metabolic treatments for known mtDNA diseases such as LHON. If ASD has a similar etiology, then these same therapeutic approaches may prove beneficial for ASD.”


  5. People with autism spectrum disorder show neural responses of anxiety on seeing social touch

    September 5, 2017 by Ashley

    From the University of Haifa press release:

    People with strong signs of autism spectrum disorder (ASD) show neural signs of anxiety when they see social touch and report unpleasant feelings about social touch by comparison to people with weak signs of ASD. This finding has emerged from a new study undertaken at the University of Haifa. “Until now, it was clear that many people with ASD dislike touch. This study enables us to understand that they actually experience touch in a similar way to anxiety,” explains Leehe Peled-Avron, a doctorate student in the Department of Psychology, who undertook the study.

    The autism spectrum is a developmental disorder characterized by difficulties in creating, understanding, and maintaining social relationships. Some 70-80 percent of people with ASD suffer from hypersensitivity or undersensitivity to neural stimulation through the various senses, including sight, touch, and taste. Some parents of children with ASD report that their children stiffen when touched, try to avoid touch, and prefer to be touched on their own terms. Until now, however, researchers did not understand exactly what causes this sensitivity, and above all — how people with ASD feel when they are exposed to touch.

    The present study, published in the journal Autism Research, was authored by Prof. Simone Shamay-Tsoory and doctorate student Leehe Peled-Avron from the Department of Psychology at the University of Haifa. The researchers sought to examine the differences in the neural response to social interaction, including human touch, between people with ASD and people without the disorder.

    Fifty-four participants were divided into two groups: one group of people with ASD who have a high level of social functioning, and one group without signs of ASD. The participants were shown 260 pictures in four categories: social touch between two people photographed in natural conditions, such as malls, parties, social events, and so forth; social interaction between the same people without touch; two everyday inanimate objects touching; and two inanimate objects not touching.

    The results of the study show that people with ASD reported unpleasant sensations when they watched social touch, compared to people without ASD. The examination of their brain waves showed that when they watched social interaction including touch, the neural signals in their brain were ones that we recognize as signals of someone in a state of anxiety. It was also found that these neural signals of anxiety increase the stronger the patterns of ASD. In other words, the higher a person is diagnosed on the autistic spectrum, the stronger their neural signals, possibly reflecting a greater level of anxiety at social touch. When the participants watched the same social interactions without touch, these signals were not present, showing that it was the element of touch that created the anxiety, and not the social interaction. “Similar neural signals to those we found have been reported in studies on phobias. If someone suffers from a specific trauma and we show them the traumatic object, the neural signals that result are identical to those we found in the study,” Peled-Avron explains.

    “The results of this study improve our understanding of people diagnosed with ASD. Social touch is an integral part of our lives, in both happy and sad events, and now we can understand why for some people on the autistic spectrum all these events arouse anxiety. As well as understanding them, this insight may be very helpful for therapists, who can offer therapy focusing on anxiety in a similar manner to therapy for phobias, whether by means of psychotherapy or medication,” the researchers concluded.


  6. Gut microbes may talk to the brain through cortisol

    September 4, 2017 by Ashley

    From the University of Illinois College of Agricultural, Consumer and Environmental Sciences press release:

    Gut microbes have been in the news a lot lately. Recent studies show they can influence human health, behavior, and certain neurological disorders, such as autism. But just how do they communicate with the brain? Results from a new University of Illinois study suggest a pathway of communication between certain gut bacteria and brain metabolites, by way of a compound in the blood known as cortisol. And unexpectedly, the finding provides a potential mechanism to explain the characteristics of autism.

    “Changes in neurometabolites during infancy can have profound effects on brain development, and it is possible that the microbiome — or collection of bacteria, fungi, and viruses inhabiting our gut — plays a role in this process,” says Austin Mudd, a doctoral student in the Neuroscience Program at U of I. “However, it is unclear which specific gut bacteria are most influential during brain development and what factors, if any, might influence the relationship between the gut and the brain.”

    The researchers studied 1-month-old piglets, which are remarkably similar to human infants in terms of their gut and brain development. They first identified the relative abundances of bacteria in the feces and ascending colon contents of the piglets, then quantified concentrations of certain compounds in the blood and in the brain.

    “Using the piglet as a translatable animal model for human infants provides a unique opportunity for studying aspects of development which are sometimes more difficult or ethically challenging to collect data on in human infants,” Mudd says. “For example, in this study we wanted to see if we could find bacteria in the feces of piglets that might predict concentrations of compounds in the blood and brain, both of which are more difficult to characterize in infants.”

    The researchers took a stepwise approach, first identifying predictive relationships between fecal bacteria and brain metabolites. They found that the bacterial genera Bacteroides and Clostridium predicted higher concentrations of myo-inositol, Butyricimonas positively predicted n-acetylaspartate (NAA), and Bacteroides also predicted higher levels of total creatine in the brain. However, when bacteria in the genus Ruminococcus were more abundant in the feces of the piglets, NAA concentrations in the brain were lower.

    “These brain metabolites have been found in altered states in individuals diagnosed with autism spectrum disorder (ASD), yet no previous studies have identified specific links between bacterial genera and these particular metabolites,” Mudd notes.

    The next step was to determine if these four bacterial genera could predict compounds in the blood. “Blood biomarkers are something we can actually collect from an infant, so it’s a clinically relevant sample. It would be nice to study an infant’s brain directly, but imaging infants is logistically and ethically difficult. We can, however, obtain feces and blood from infants,” says Ryan Dilger, associate professor in the Department of Animal Sciences, Division of Nutritional Sciences, and Neuroscience Program at U of I.

    The researchers found predictive relationships between the fecal microbiota and serotonin and cortisol, two compounds in the blood known to be influenced by gut microbiota. Specifically, Bacteroides was associated with higher serotonin levels, while Ruminococcuspredicted lower concentrations of both serotonin and cortisol. Clostridium and Butyricimonas were not associated strongly with either compound.

    Again, Mudd says, the results supported previous findings related to ASD. “Alterations in serum serotonin and cortisol, as well as fecal Bacteroides and Ruminococcus levels, have been described in ASD individuals.”

    Based on their initial analyses, the researchers wanted to know if there was a three-way relationship between Ruminococcus, cortisol, and NAA. To investigate this further, they used a statistical approach known as “mediation analysis,” and found that serum cortisol mediated the relationship between fecal Ruminococcus abundance and brain NAA concentration. In other words, it appears that Ruminococcus communicates with and makes changes to the brain indirectly through cortisol. “This mediation finding is interesting, in that it gives us insight into one way that the gut microbiota may be communicating with the brain. It can be used as a framework for developing future intervention studies which further support this proposed mechanism,” Dilger adds.

    “Initially, we set out to characterize relationships between the gut microbiota, blood biomarkers, and brain metabolites. But once we looked at the relationships identified in our study, they kept leading us to independently reported findings in the autism literature. We remain cautious and do not want to overstate our findings without support from clinical intervention trials, but we hypothesize that this could be a contributing factor to autism’s heterogenous symptoms,” Mudd says. Interestingly, in the time since the researchers wrote the paper, other publications have also reported relationships between Ruminococcus and measures of brain development, supporting that this might be a promising area for future research.

    Dilger adds, “We admit this approach is limited by only using predictive models. Therefore, the next step is to generate empirical evidence in a clinical setting. So it’s important to state that we’ve only generated a hypothesis here, but it’s exciting to consider the progress that may be made in the future based on our evidence in the pre-clinical pig model.”


  7. MRI reveals striking brain differences in people with genetic autism

    August 23, 2017 by Ashley

    From the Radiological Society of North America press release:

    In the first major study of its kind, researchers using MRI have identified structural abnormalities in the brains of people with one of the most common genetic causes of autism, according to a new study published online in the journal Radiology. The abnormalities visible on brain images corresponded to cognitive and behavioral impairments in the study group, suggesting a future role for imaging in identifying people with autism who are in most urgent need of intervention.

    Autism spectrum disorders are a group of developmental problems, affecting more than 3.5 million people in the U.S., according to the Centers for Disease Control and Prevention. Symptoms typically appear early in life and frequently include communication problems and repetitive behaviors. Many people with autism have abnormalities at a specific site on the 16th chromosome known as 16p11.2. Deletion or duplication of a small piece of chromosome at this site is one of the most common genetic causes of autism spectrum disorder.

    “People with deletions tend to have brain overgrowth, developmental delays and a higher risk of obesity,” said study author Julia P. Owen, Ph.D., a brain researcher at the University of Washington in Seattle, who was at the University of California in San Francisco (UCSF) during the study. “Those with duplications are born with smaller brains and tend to have lower body weight and developmental delays.”

    The researchers at UCSF and four other sites performed structural MRI exams on 79 deletion carriers, ranging in age from 1 to 48, and 79 duplication carriers, ages 1 to 63, along with 64 unaffected family members and 109 participants in a control group.

    The participants completed a battery of cognitive and behavioral tests, and neuroradiologists reviewed the brain images for development-related abnormalities. The results showed some striking differences in the brain structures of deletion and duplication carriers compared with non-carriers. For instance, the corpus callosum, the fiber bundle that connects the left and right sides of the brain, was abnormally shaped and thicker in the deletion carriers but thinner in the duplication carriers, compared to the control group and familial non-carriers.

    Other stark differences were apparent. The deletion carriers displayed features of brain overgrowth, including the extension of the cerebellum, the bottom back part of the brain, toward the spinal cord. The duplication carriers showed characteristics of brain undergrowth, such as decreased white matter volume and larger ventricles — the cavities in the brain filled with cerebrospinal fluid.

    When the researchers compared cognitive assessments to imaging findings, they found that the presence of any imaging feature associated with the deletion carriers — such as a thicker corpus callosum — indicated worse daily living, communication and social skills, compared to deletion carriers without any radiological abnormalities. For the duplication carriers, the presence of decreased white matter and corpus callosal volume and increased ventricle size was associated with decreased full-scale and verbal IQ scores, compared to duplication carriers without those findings.

    Key to the study’s strength was its access to a large, diverse group of 16p11.2 deletion and duplication carriers, according to senior author Elliott Sherr, M.D., Ph.D., head of the Brain Development Research Program at UCSF.

    “Often studies like this focus on high-functioning individuals, but this was an ‘all-comers’ group,” he said. “We didn’t do mathematical algorithms but rather used the trained eyes of neuroradiologists to evaluate the scans of a full range of individuals. When you look at a broad range of people like this, from developmentally normal to more significantly challenged, you’re better able to find these correlations.”


  8. Study suggests autism may reflect excitation-inhibition imbalance in brain

    August 18, 2017 by Ashley

    From the Stanford University Medical Center press release:

    A study by Stanford University investigators suggests that key features of autism reflect an imbalance in signaling from excitatory and inhibitory neurons in a portion of the forebrain, and that reversing the imbalance could alleviate some of its hallmark symptoms.

    In a series of experiments conducted on a mouse model of the disorder, the scientists showed that reducing the ratio of excitatory to inhibitory signaling countered hyperactivity and deficits in social ability, two classic symptoms of autism in humans.

    The study will be published Aug. 2 in Science Translational Medicine. Karl Deisseroth, professor of bioengineering and of psychiatry and behavioral sciences, is the study’s senior author. The lead author is former graduate student Aslihan Selimbeyoglu, PhD.

    In 2011, Deisseroth’s group published a study in Nature showing that autismlike behavioral deficits could be induced in ordinary mice by elevating the ratio of excitatory to inhibitory neuronal firing patterns in the mice’s medial prefrontal cortex. The new study shows that decreasing that ratio restores normal behavior patterns in a strain of lab mice bioengineered to mimic human autism. These mice carry a mutation equivalent to a corresponding mutation in humans that is associated with autism spectrum disorder.

    Autism incidence increasing

    For reasons that are not understood, the incidence of autism spectrum disorder has increased steadily in recent years, said Deisseroth, a practicing psychiatrist. Around 1 in 80 American children may be diagnosed with the disorder, which is characterized by repetitive behaviors and difficulty with social interaction. To date, there are no medications that treat the fundamental underpinnings of the disorder.

    “In all of psychiatry, there’s no lab test that can diagnose this condition,” said Deisseroth. “It’s been associated with numerous genetic variants, many of which appear to exert only small individual influences.”

    Deisseroth, who holds the D.H. Chen Professorship, notes that UCSF psychiatrist John Rubenstein and his colleagues, among others, have theorized that an excitation-inhibition imbalance might account for these phenomena. While myriad genetic variations contribute to autism, many of them may do so by impairing, in diverse ways, a single process or a small number of processes necessary for overall healthy brain function, such as a balance between excitatory and inhibitory signaling in key brain regions. One of those regions is the medial prefrontal cortex, which plays a major role in executive functions, such as planning, prediction, attention and integrating information from other individuals’ behaviors and speech for clues as to what they might be thinking.

    Testing the hypothesis

    “Social interaction may be the hardest thing a mammal can do,” Deisseroth said. “It’s an immensely complex phenomenon that requires rapid, highly integrated communication among disparate, distant parts of the brain. Specific brain states well-suited for rich information handling may be needed for effective social communication and behavior.”

    To test the excitation-inhibition balance hypothesis, the Stanford scientists launched a set of experiments employing the mutant mice, which display hyperactive behavior and impaired social interaction. Interestingly, these mice also share a less visible characteristic with humans carrying the equivalent mutation: a shortage, compared with normal mice and humans, of parvalbumin neurons, a particular category of inhibitory nerve cell found throughout the brain. In a 2009 Nature paper, Deisseroth and his team reported that parvalbumin neuron activity can improve the information-handling capacity of forebrain neurons.

    The researchers used optogenetics, an advanced laboratory technology that Deisseroth pioneered, to insert genes for two types of light-sensitive proteins, or opsins, into two distinct sets of neurons in the medial prefrontal cortex of the mice. The researchers inserted one type of opsin into parvalbumin inhibitory neurons in that region of the mice’s brains. It made the neuron more excitable if it received a pulse of blue light, delivered via an implanted optical fiber.

    The other opsin, also activated with a pulse of blue light, had the opposite effect: When activated, it rendered the neuron on which it sat more resistant to firing. The scientists put this inhibitory opsin in a set of excitatory medial prefrontal cortex neurons called pyramidal neurons.

    Reducing the excitation-inhibition ratio by either diminishing the excitability of the pyramidal neurons or by increasing the excitability of the parvalbumin neurons led to the same result in the mice: more time spent engaging in social encounters with other mice and less hyperactivity during those encounters or when the mice were by themselves.

    “Excitation-inhibition balance can take many forms and may be important at different stages of life,” Deisseroth said. “Together, these findings suggest that this form of regulating the ratio of excitatory- to inhibitory-cell firing in the medial prefrontal cortex may be significant in normal social behavior and in autism.”


  9. Study looks at effects of cognitive behavior therapy on parents of children with autism

    August 17, 2017 by Ashley

    From the York University press release:

    Parents of children with autism experience a greater impact from their child’s therapy than once thought, according to new research out of York University’s Faculty of Health.

    Jonathan Weiss, Associate Professor in the Department of Psychology, Faculty of Health and CIHR Chair in Autism Spectrum Disorders (ASD) Treatment and Care Research, discovered that parents who participate in cognitive therapy with their children with autism also experience a real benefit that improves the family experience.

    Approximately 70 per cent of children with autism struggle with emotional or behavioural problems, and may benefit from cognitive behaviour therapy to improve their ability to manage their emotions.

    “Most of the time when parents bring in their kids for cognitive behaviour therapy, they are in a separate room learning what their children are doing, and are not being co-therapists,” said Weiss. “What’s unique about what we studied is what happens when parents are partners in the process from start to finish. Increasingly we know that it’s helpful for kids with autism, specifically, and now we have proven that it’s helpful for their parents too.”

    Parents who took part in the study were involved in a randomized controlled trial. They were asked to complete surveys before and after the treatment and were compared to parents who had not begun therapy.

    Weiss and Ph.D student Andrea Maughan, examined changes in parent mental health, mindfulness, and perceptions of their children, during a trial of cognitive behaviour therapy for 57 children with ASD aged 8-12 who did not have an intellectual disability. The study, published in the Journal of Autism and Developmental Disorders, showed that parents who participated in cognitive therapy with their children, experienced improvements in their own depression, emotion regulation, and mindful parenting.

    “The research showed that parents improved their abilities to handle their own emotions and to see themselves in a more positive light,” said Weiss. “It helped them to become more aware of their parenting and all of the good they do as parents.”

    In the study, parents were co-therapists with their child’s therapist and were tasked with employing the same strategies alongside their children. This allowed the parents learn to help themselves in the process. Parents were required to write down their children’s thoughts during activities.

    “As a parent participating in the SAS:OR Program, I have grown as much as my son did. I used to use a “one size fits all” strategy with my son — now he and I have many tools to manage through difficult moments,” said Jessica Jannarone, a parent involved in study. “The ability to talk about our feelings, identify triggers, and think proactively about approaches has brought both positivity and comfort to our lives. Watching my son develop in this program and find a way to start handling his feelings has been the greatest gift of all.”

    Weiss added the findings also speak to the importance for health care providers to involve parents in the process of delivering care to children with autism.

    “We know parents of children with autism, in addition to all the positive experiences they have, also experience high levels of distress. So if we can do something to reduce that, we have a responsibility to try to do so.”


  10. Study suggests people with autism are less surprised by the unexpected

    August 16, 2017 by Ashley

    From the University College London press release:

    Adults with autism may overestimate the volatility of the world around them, finds a new UCL study published in Nature Neuroscience.

    The researchers found that adults with autism were less surprised by unexpected images in a simple learning task than adults without autism, and those who were the least surprised had the most pronounced symptoms.

    “We know from previous studies that people with autism often aren’t surprised by things that would surprise other people,” said lead author Dr Rebecca Lawson (UCL Wellcome Trust Centre for Neuroimaging). “Our results suggest that this may be because of differences in how people with autism build expectations. Our expectations bias our behaviour in subtle ways, so being less susceptible to these effects may result in strengths as well as difficulties.”

    Insistence on sameness and intolerance of change are part of the diagnostic criteria for autism, but there has been little research addressing how people with autism represent and respond to unexpected changes to their environment.

    In this study, 24 adults with autism and 25 adults without autism completed a task that involved learning to expect to see different pictures on a computer screen after hearing either a high or low sound.

    The researchers applied computational modelling to the data to characterize each person’s learning process. They found that adults with autism tend to overestimate how changeable the environment is, which reduces how much their prior expectations guide their behaviour.

    The adults with autism learned the task well enough overall, but showed differences in updating their expectations when the environment unexpectedly became more volatile.

    “When we’re uncertain about our own beliefs, such as under volatile conditions, we’re driven more by our senses than our prior expectations. If people with autism are more often expecting volatility, that could help explain their propensity to sensory overload, enhanced perceptual functioning and context insensitivity,” said Dr Lawson.

    The study found that the ability to form expectations about upcoming pictures was related to the severity of communication problems in people with autism. Senior author Professor Geraint Rees (UCL Wellcome Trust Centre for Neuroimaging) said: “The idea that differences in how people with autism build visual expectations may link to social difficulties is an intriguing possibility, and one that we would like to pursue further in consultation with members of the autism community.”

    The computational measures of learning and surprise were also linked to changes in pupil size, which is believed to reflect the function of brain chemicals called neuromodulators, such as noradrenaline.

    “This work opens up the possibility of using computational modelling with more direct measures of brain function to help us understand the neural basis of differences in how we learn about changes in the environment,” said co-author Dr Christoph Mathys (SISSA — Trieste, Italy).

    Dr Lawson added: “The individual differences in how people represent and respond to the world are often more striking than the similarities. This research represents an important advance in our understanding of how people with autism see the world differently.”