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Why Does Autism Affect The Brain

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New Research Sheds Light On Previously Under

Autism Study Shows Link to Brain Overgrowth

The findings suggest that we should not blindly assume that everything found in males with autism applies to females.

Dr Meng-Chuan Lai

Autism affects different parts of the brain in females with autism than males with autism, a new study reveals. The research is published today in the journal Brain as an open-access article.

Scientists at the Autism Research Centre at the University of Cambridge used magnetic resonance imaging to examine whether autism affects the brain of males and females in a similar or different way. They found that the anatomy of the brain of someone with autism substantially depends on whether an individual is male or female, with brain areas that were atypical in adult females with autism being similar to areas that differ between typically developing males and females. This was not seen in men with autism.

One of our new findings is that females with autism show neuroanatomical masculinization, said Professor Simon Baron-Cohen, senior author of the paper. This may implicate physiological mechanisms that drive sexual dimorphism, such as prenatal sex hormones and sex-linked genetic mechanisms.

Autism affects 1% of the general population and is more prevalent in males. Most studies have therefore focused on male-dominant samples. As a result, our understanding of the neurobiology of autism is male-biased.

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Do These Differences Impact Symptoms

Most likely the result of these connections manifest into the signs and the symptoms that we see. However, Dr. Anderson cautions that it is hard to know exactly what brain connection correlates to what sign. Ultimately, theres still an awful lot that we need to know, he says. Just looking at that brain imaging, we arent really able to explain all of the behaviors that we see.

Cohens D Effect Sizes

The t-statistic for the factor diagnosis in each linear mixed effects model was used to calculate Cohens d, with

where n1 and n2 are the number of cases and controls, and df the degrees of freedom.

The latter was derived from the lme summary table in R, but can also be calculated using df=obs , where obs equals the number of observations, x1 the number of groups and x2 the number of factors in the model.

The 95% confidence intervals for Cohens d were calculated using 95% CI=d±1.96 SE, with the standard error around Cohens d calculated according to:

For visualization of cerebral cortical results, Cohens d values were loaded into Matlab , and 3D images of left hemisphere inflated cortical and subcortical structures were obtained using FreeSurfer-derived ply files.

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How Does The Autism Brain Change Through The Lifespan

Autism spectrum disorder is generally a lifelong condition, but there is currently very little understanding of how the brain changes in people with ASD as they age.

One researcher who is focusing on changes in the brain in people with autism during development is Dr. Cyndi Schumann at the UC Davis MIND Institute. Dr. Schumann has carried out magnetic resonance imaging studies on people with autism as well as microscopic studies on postmortem tissue for multiple age groups to describe the different phases of brain development in those with ASD.1 When her team looked specifically at the amygdala, a brain region responsible for processing emotional information, they found that changes depended on the age studied. As you can see from the drawing below, there is a phase of early amygdala overgrowth in ASD followed, at later ages, by a decrease in neurons. What causes this alteration in the trajectory of amygdala growth is not known but may have profound effects on the behavior of individuals with ASD.

Research studies like these need your help. To learn more about the Autism BrainNet and to receive more information about why it takes brains to understand autism, go to www.takesbrains.org/signup.

  • Morgan JT, Barger N, Amaral DG, Schumann CM. Stereological study of amygdala glial populations in adolescents and adults with autism spectrum disorder. PloS one. 2014;9:e110356.
  • Linear Mixed Effects Random

    FCTI

    Model: linear mixed effects models were fitted separately for each cortical regional surface and thickness AI, as well as the total hemispheric surface area and mean thickness AI, and the subcortical volume AIs. This was accomplished by means of mega-analysis incorporating data from all 54 data sets, using the nlme package in R. All models included the same fixed- and random effects, and had the following formulation:

    where AI reflects the AI of a given brain structure, and diagnosis , ASD), sex , females) and data setwere coded as factor variables, with data set having 54 different categories. Age was coded as a numeric variable.

    The Maximum Likelihood method was used to fit the models. Subjects were omitted if data were missing for any of the predictor variables . The ggplot2 package in R was used to visualize residuals . Collinearity of predictor variables was assessed using the usdm package in R .

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    When Does Autism Develop

    The new study shows how the mutation of a gene that has been linked to autism can lead to localized defects in the brain, said Dr. Nenad Sestan, a brain development specialist and a professor of neuroscience at the Yale University School of Medicine.

    These radial glia are the stem cells of the brain, Sestan, who was not involved in the new study, said. They create all the neurons in the cortex and guide them to their final destination.

    Genetic studies have focused on hundreds of genes that could be involved in the development of autism, said Alex Kolodkin, an expert in neural development and the Charles J. Homcy and Simeon G. Margolis professor of neuroscience at the Johns Hopkins School of Medicine. And a significant fraction end up as being involved, he said.

    The issue, he said, is now figuring out how to link the genes known to be associated with autism to the defects in brain wiring.

    The research also suggests that some of the disruptions that may contribute to autism could be happening earlier than we thought in the first three months of fetal development, Sestan said.

    Linda Carroll is a regular health contributor to NBC News and Reuters Health. She is coauthor of “The Concussion Crisis: Anatomy of a Silent Epidemic” and “Out of the Clouds: The Unlikely Horseman and the Unwanted Colt Who Conquered the Sport of Kings.”;

    How Is The Structure Of The Brain Different

    The neuroanatomy of autism is difficult to describe, Dr. Culotta says. So it might be easier to talk about the architecture of the brain and how the autistic brain may differ.

    So whats different in the structure of this three-pound organ? Lets start with a quick anatomy refresher: First of all, the brain is split into two halves or hemispheres. It is these two hemispheres that we get the idea of a left brain and a right brain. In reality, our thinking and cognitive processes bounce back and forth between the two halves. Theres a little bit of difficulty in autism communicating between the left and right hemispheres in the brain. Theres not as many strong connections between the two hemispheres, Dr. Anderson says.

    In recent years, science has found that the hemispheres of ASD brains have slightly more symmetry than those of a regular brain. This small difference in asymmetry isnt enough to diagnosis ASD, according to a report in Nature Communications. And, exactly how the symmetry may play into autisms traits is still be researched.

    Now, were going to get a little technical. Grey matter ripples into peaks and troughs called gyri and sulci, respectively. According to researchers from San Diego State University, these deep folds and wrinkles may develop differently in ASD. Specifically, in autistic brains there is significantly more folding in the left parietal and temporal lobes as well as in the right frontal and temporal regions.

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    Quick Facts About Autism

    • Autism occurs in approximately 1 out of every 59 children in the U.S.
    • Autism is the third most common developmental disorder in the U.S.,affecting at least 500,000 people.
    • Autism is seen more often in boys; four or five boys will have autismcompared to one girl. But girls with autism are often more severelyaffected than boys and score lower on intelligence tests.
    • Leo Kanner first described autism as the “inability to relatethemselves in the ordinary way to people and situations from the beginningof life” in the 1943 paper “Autistic Disturbances of Affective Contact.”
    • Autism usually is seen within the first three years of life.
    • Some people with autism are gifted in certain areas such as math ormusic.
    • Autism has also been called “early infantile autism,” “childhoodautism,” “Kanner’s autism,” and “pervasive developmentaldisorder.”

    The Brain Of Children With Autism Spectrum Disorder

    Autism & Pediatric Diseases : What Parts of the Brain Does Autism Affect?

    24 August, 2020

    If the brain of a child with autism spectrum disorder was a house, every room would be filled with noise, itd have complex wiring all over it, and its walls would be very sensitive to almost any stimulus. This excess of synapses or neural connections produces particular alterations in every child.

    Scientific advances dont really matter. Its useless to continue learning about these neurological development disorders that affect a significant part of our population. The lack of awareness, stereotypes, and the misconceptions that we have about those who suffer from these disorders keep us from appreciating them as they are.

    Undoubtedly, the problematic behavior of children and teenagers with ASD can put our patience to the test. They may have a privileged mind or serious intellectual deficits. However, despite their ever-so-enigmatic world, they surprise us with their strengths, sensibilities, needs, and affection.

    Their families are commendable. They promote ceaseless and energetic love that not only has to deal with stereotypes, but also tries to create alliances with other social agents: doctors, specialists, teachers, psychologists, and everyone else whos devoted to these children.

    Therefore, we can help them by trying to better understand their internal reality. Lets delve deeper into this.

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    Gene Mutation In The Brain May Be Early Clue To Autism Study Suggests

    Mutations of a certain gene may contribute to autism by interfering with normal brain development, a new study suggests.

    The gene, which is mutated in some people with autism, affects cells that set up the framework for the organization of a fetuss developing cortex, according to the study published in Neuron.

    Those cells, called radial glia, can be viewed like the framing timbers of a house under construction. If the houses framing is off, then the rest of the construction will be affected.

    Each of the radial glia divide and make neurons and serve as the guide for where those neurons go, said study coauthor Eva Anton, a professor at the University of North Carolina Neuroscience Center. They enable the organization of neurons in the brain that underlies functional circuits.

    Disruption of this early organization, may be one of the contributors causing some of the brain malformations associated with autism, Anton said.

    Gender Differences In Diagnosis

    Autism is more commonly diagnosed in males than in females across age groups . When screening the entire population using gold standard assessments, current estimates suggest around three males receive an autism diagnosis for every female; however, in clinical samples who have already received an autism diagnosis, that ratio is higher at over four males to each female . In individuals with intellectual disability, the ratio is closer to 2:1 .

    When attempting to account for the discrepancies in diagnosis, researchers have drawn upon two distinct ideas, which are contrasting but not mutually exclusive. One argues that there is something inherent in being female that protects females from the likelihood of developing autism . The other proposes that females may be more likely to develop autism than we currently estimate, but that diagnostic biases and variation in the ways autism is expressed in females mean we do not pick up autism in females to the same degree as males .

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    Early Signs Of Autism Include:

    • Failure to respond to their name by one year of age.
    • Not pointing at interesting objects by the age of fourteen months.
    • Not playing pretend by eighteen months of age.
    • Inability to understand the feelings displayed by others, or to talk about their own.
    • Delayed skills in the areas of speech and communication.
    • Echolalia, or excessive repetition of certain phrases or single words.
    • Responding to questions with unrelated answers.
    • Being particularly sensitive to minor changes in personal environment and routines.
    • Exhibiting interests in an obsessive manner.
    • Repetitive motions like hand flapping, rocking their body, or spinning in circles.
    • Reacting oddly to the taste, smell, texture, appearance, or sound of everyday things.

    Regular visits to a pediatrician can help identify any areas of concern with regard to typical developmental milestones.

    Overly Persistent Brain Connections

    Secrets of the Autistic Mind

    First, the researchers conducted functional MRI scans on 90 male participants, of which 52 had a diagnosis of autism and 38 did not. The participants with autism were aged between 19 and 34, while the rest of the volunteers who acted as the control group had ages ranging between 20 and 34.

    Then, to confirm the initial findings, the specialists compared their data with that collected from a further 1,402 people who participated in the Autism Brain Imaging Data Exchange study. Of these, 579 participants had autism. The remaining 823 participants did not have autism and acted as the control group.

    Dr. Anderson and team used a novel fMRI method to explore brain activity in the participants on the current study. More specifically, they looked at the duration of connections established across brain regions.

    We dont have good methods for looking at the brain on these timescales. Its been a blind spot because it falls in between typical MRI and studies, explains Dr. Anderson.

    Thanks to the fMRI scans, the researchers were able to confirm that in the brains of people with autism, connections persist for more extended periods than they do in the brains of neurotypical individuals. In other words, in autism, the brain finds it harder to switch between processes.

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    How Is Asd Diagnosed

    ASD symptoms can vary greatly from person to person depending on the severity of the disorder. Symptoms may even go unrecognized for young children who have mild ASD or less debilitating handicaps.

    Autism spectrum disorder is diagnosed by clinicians based on symptoms, signs, and testing according to the Diagnostic and Statistical Manual of Mental Disorders-V, a guide created by the American Psychiatric Association used to diagnose mental disorders. Children should be screened for developmental delays during periodic checkups and specifically for autism at 18- and 24-month well-child visits.

    Very early indicators that require evaluation by an expert include:

    • no babbling or pointing by age 1
    • no single words by age 16 months or two-word phrases by age 2
    • no response to name
    • excessive lining up of toys or objects
    • no smiling or social responsiveness

    Later indicators include:

    • impaired ability to make friends with peers
    • impaired ability to initiate or sustain a conversation with others
    • absence or impairment of imaginative and social play
    • repetitive or unusual use of language
    • abnormally intense or focused interest
    • preoccupation with certain objects or subjects
    • inflexible adherence to specific routines or rituals

    Apparent Reversal Of Neurobiological Defects In The Adult

    A remarkable finding in some recently studied animal models of autistic symptoms has been the surprising degree to which autistic symptoms have been apparently reversed or ameliorated by replacing or modulating gene function after birth or even in the adult. The first example of this came with a Drosophila model of Fragile × syndrome . Normally, the mutant flies have a defect in social/courtship learning and also have defects in the axons of neurons clustered in a brain region known as the mushroom body. The Fragile × disease pathway was modulated by administration of several drugs including metabotropic glutamate antagonists that can decrease the excessive protein translation caused by mutations in FMR or even using lithium carbonate, which modulates downstream signaling of the Fragile × pathway through the kinase GSK-3. Remarkably, in flies born with fixed defects in social behavior the phenotype could be rescued almost completely in adulthood by administration of metabotropic glutamate antagonists or even lithium .

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    A Whole New Perspective

    These findings, which were consistent with data from the ABIDE study, may explain why people with autism can experience distress when exposed to numerous stimuli at once, the research team believes.

    Individuals with autism who have greater social dysfunction have an increase in synched activity in their scans, notes postdoctoral researcher Jace King, first author of the study paper.

    Now that we are looking at finer timescales, weve found a consistent story. It provides us with new tools to figure out the mechanisms that may underlie autism, King adds.

    Nevertheless, the researchers note that their study faced one fundamental limitation namely that it worked with male participants only, which may not offer the full picture of what characterizes autism in the brain. Still, they will not stop at this study and hope to expand this research.

    We want to compare the results from this analysis to more traditional methods. This is a whole new perspective into how autism works in the brain and can help us develop strategies for treatment and finding medications that might be more effective to ease the symptoms of the disorder.

    Dr. Jeff Anderson

    Autism Symptomology In Girls

    How does stress affect the autistic brain? [Q&A]

    Studies have shown that there is a male bias in diagnosing autism due to differing symptoms including fewer restricted and repetitive behaviors and externalizing behavioral problems in females . Social factors make it harder to diagnose autism in girls and they may need to have more behavioral issues or cognitive disability than boys in order to be diagnosed. Girls with autism may score the same on indicators of friendship or empathy as boys, but not the same as typically-developing girls. They want to socialize more than boys with autism, and have higher rates of depression and suicidal thoughts as teens. Preliminary research shows that the hallmark brain differences in autism vs. typical peers seems to hold true for boys, but not girls. A new forthcoming study by Kevin Pelphrey, PhD, director of the Autism and Neurodevelopmental Disorders Institute at George Washington University, will discuss Listening to our Daughters : Insights from the Study of Girls and Women Living with Autism, and is available in as archived webinar at www.IANcommunity.org.

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