Autism

Posted on Autism

The strong performance of an autism screener – could help with early intervention. Maybe!

HSE researchers compared expressive and receptive language abilities of Russian-speaking children with autism for the first time

With one in 44 children in the United States having autism, early detection and intervention are integral to improving outcomes. Because autism is diagnosed based on behavior, and there are not yet reliable biomarkers to detect the likelihood of autism, there is a need for standardized screening to identify children at high likelihood for autism and to refer them for diagnostic and intervention services at as young an age as possible.

However, Robins and her colleague Andrea Wieckowski, PhD, an assistant professor in the Autism Institute, have found that use of these measures in research and clinical practice often differs from the original validation studies. This limits people’s ability to understand and measure how M-CHAT(-R/F) performs in detecting autism.

Newly published in JAMA Pediatrics, a study by Wieckowski, Robins and their co-authors systematically reviewed and analyzed factors that may lead to different performance estimates of the M-CHAT(-R/F) tests. The research team reviewed studies published between January 2001 and August 2020 and found 50 studies that provided information on M-CHAT(-R/F)’s performance as an autism screener.

“M-CHAT(-R/F) shows strong performance as an autism screener,” said Wieckowski “We found that across the studies, there was 83% sensitivity, or ability to detect autism when present. Specificity, or ability to accurately rule out autism, was 94%, indicating its strong performance.”

However, there was also wide variability in results. Higher performance was reported in studies that used low-likelihood of autism samples — also known as “population-based” samples — as opposed to high-likelihood samples, such as samples of children with older siblings on the autism spectrum or other factors that increase likelihood of autism.

Performance of M-CHAT(-R/F) also varied according to confirmation strategies and use of Follow-Up. Specifically, whether case-confirmation strategies occurred around the same time as screening (concurrent) or when children were older (prospective), or whether the study used the structured Follow-Up for children who scored in the moderate range on the initial questionnaire impacted the screener’s performance. Other factors that influenced performance of M-CHAT(-R/F) screening included use of non-English translations of the test, versus primarily English screening, and the size of the study sample.

The authors suggest that the finding of high variability in the sensitivity and specificity based on these factors should be considered when using the test in clinical and research settings. Overall, the results of this study support the current recommendations from the American Academy of Pediatrics (AAP) for universal autism screening at 18- and 24-month well-child check-ups.

“For screening to be effective, protocols should adhere to the recommended use, and children who screen positive should be referred for evaluation and early intervention without delay,” said Wieckowski.

According to the research team, currently many pediatric practices do not adhere to the AAP guidelines to screen all children. Others deviate from recommended use by not administering follow-up, not repeating screening, and not referring positive cases for evaluation and early intervention. They add that findings from the U.S. Preventive Services Task Force, which found insufficient evidence to support universal screening, lead to confusion about best practices for early detection of autism.

“It is our hope that this systematic review and meta-analysis, which is the most thorough examination of M-CHAT(-R/F) to date, will be used to improve access to high-quality screening for all children and to identify autism in very young children,” said Robins.

Posted on Autism

Autism and No Sleep Is Common – Does this story ring any bells?

Autism and No Sleep
Autism and No Sleep


She did not sleep for over 40 hours. Our autistic daughter has periods where sleep is just hard to get. We have experienced this throughout her life. As a toddler, she had many 4-hour nights. As a kid, 3 am seems to be her internal alarm clock. It is something we did not know about autism but something we have learned, and we are pretty good about managing the lack of sleep as parents.


Posted on Autism

A giant step forward in understanding autism

Like a tree: morphology and function of pyramidal neurons in autism spectrum disorders.


The image of the tree is used to illustrate the morphology and function of pyramidal neurons in autism spectrum disorders. These neurons are one of the main integrators of information in the cerebral cortex, with long “branches” and “roots” representing dendrites. The small “leaf-like” projections are the dendritic spines, where the excitatory synapses connect one neuron to another. The blurred sections of the image represent the altered integration and perception of sensory information from the outside world, discovered by Diana E. Mitchell, Soledad Miranda-Rottmann and colleagues. CREDIT © Photo and drawing by Roberto Araya and Soledad Miranda-Rottmann. Photo was taken at Westmount Park, Montreal, Canada.

Results of a new study led by Roberto Araya, a Canadian neuroscientist, biophysicist and researcher at the CHU Sainte-Justine Research Centre, in Montreal, show that in Fragile X syndrome (FXS), the most common cause of autism, sensory signals from the outside world are integrated differently, causing them to be underrepresented by cortical pyramidal neurons in the brain.

This phenomenon could provide important clues to the underlying cause of the symptoms of this syndrome. The research team’s work not only provides insight into the mechanism at the cellular level, but also opens the door to new targets for therapeutic strategies.

The study was published on January 3 in the prestigious journal Proceedings of the National Academy of Sciences.

Autism is characterized by a wide range of symptoms that may stem from differences in brain development. With advanced imaging tools and the genetic manipulation of neurons, the team of researchers at the CHU Sainte-Justine Research Center was able to observe the functioning of individual neurons – specifically pyramidal neurons of cortical layer 5 – one of the main information output neurons of the cortex (the thin layer of tissue found on the surface of  the brain).

The researchers found a difference in how sensory signals are processed in these neurons.

“Previous work has suggested that FXS and autism spectrum disorders are characterized by a hyperexcitable cortex, which is considered to be the main contributor to the hypersensitivity to sensory stimuli observed in autistic individuals,” said  Araya, also a professor in the Department of Neurosciences at Université de Montréal.

“To our surprise, our experimental results challenge this generalized view that there is a global hypersensitivity in the neocortex associated with FXS. They show that the integration of sensory signals in cortical neurons is underrepresented in a murine model of FXS,” added Diana E. Michell, first co-author of the study.

A protein, FMRP, that is absent in the brains of people with FXS modulates the activity of a type of potassium channel in the brain. According to the research group’s work, it is the absence of this protein that alters the way sensory inputs are combined, causing them to be underrepresented by the signals coming out of the cortical pyramidal neurons in the brain.

Soledad Miranda-Rottmann, also first co-author of the study, attempted to rectify the situation with genetic and molecular biology techniques. “Even in the absence of the FMRP protein, which has several functions in the brain, we were able to demonstrate how the representation of sensory signals can be restored in cortical neurons by reducing the expression of a single molecule,” she said.

“This finding opens the door to new strategies to offer support to those with FXS and possibly other autism spectrum disorders to correctly perceive sensory signals from the outside world at the level of pyramidal neurons in the cortex,” concluded Araya.

“Even if the over-representation of internal brain signals causing hyperactivity is not addressed, the correct representation of sensory signals may be sufficient to allow better processing of signals from the outside world and of learning that is better suited to decision making and engagement in action.”

Posted on Autism, Epilepsy

Study reveals how CBD counters epileptic seizures – important for members of the autistic community

Microscope image


This microscope image of the brain region called the hippocampus shows the protein targeted by cannabis-derived CBD, GPR55 (red), and brain cells (blue) that send their extensions out to form the layers seen in the image. The interconnected nature of the hippocampus makes it a significant site for the initiation and spread of seizures.
Tsien et al, Courtesy of Cell Press

A study reveals a previously unknown way in which cannabidiol (CBD), a substance found in cannabis, reduces seizures in many treatment-resistant forms of pediatric epilepsy.  

Led by researchers at NYU Grossman School of Medicine, the new study found that CBD blocked signals carried by a molecule called lysophosphatidylinositol (LPI). Found in brain cells called neurons, LPI is thought to amplify nerve signals as part of normal function but can be hijacked by disease to promote seizures.

Published online February 13 in Neuron, the work confirmed a previous finding that CBD blocks the ability of LPI to amplify nerve signals in a brain region called the hippocampus. The current findings argue for the first time that LPI also weakens signals that counter seizures, further explaining the value of CBD treatment.   

“Our results deepen the field’s understanding of a central seizure-inducing mechanism, with many implications for the pursuit of new treatment approaches,” said corresponding author Richard W. Tsien, chair of the Department of Physiology and Neuroscience at NYU Langone Health.

“The study also clarified, not just how CBD counters seizures, but more broadly, how circuits are balanced in the brain,” added Tsien. “Related imbalances are present in autism and schizophrenia so that the paper may have a broader impact.”

Disease-Causing Loop

The study results build on how each neuron “fires” to send an electrical pulse down an extension of itself until it reaches a synapse, the gap that connects it to the next cell in a neuronal pathway. When it reaches the cell’s end before the synapse, the pulse triggers the release of compounds called neurotransmitters that float across the gap to affect the next cell in line. Upon crossing, such signals either encourage the cell to fire (excitation), or apply the brakes on firing (inhibition). Balance between the two are essential to brain function; too much excitation promotes seizures.   

The new study looked at several rodent models to explore mechanisms behind seizures, often by measuring information-carrying electrical current flows with fine-tipped electrodes. Other experiments looked at the effect of LPI by genetically removing its main signaling partner, or by measuring the release of LPI following seizures.

The tests confirmed past findings that LPI influences nerve signals by binding to a protein called G-coupled receptor 55 (GPR55), on neuron cell surfaces. This LPI-GPR55 presynaptic interaction was found to cause the release of calcium ions within the cell, which encouraged cells to release glutamate, the main excitatory neurotransmitter. Further, when LPI activated GPR55 on the other side of the synapse, it weakened inhibition, by decreasing the supply and proper arrangement of proteins necessary for inhibition. Collectively, this creates a “dangerous” two-pronged mechanism to increase excitability, say the authors.  

The research team found that either genetically engineering mice to lack GPR55, or treating mice with plant-derived CBD prior to seizure-inducing stimuli, blocked LPI-mediated effects on both excitatory and inhibitory synaptic transmission. While prior studies had implicated GPR55 as a seizure-reducing target of CBD, the current work provided a more detailed, proposed mechanism of action.

Posted on Autism

Brain-wave data and hearing tests may help diagnose autism earlier

New study demonstrates link between brain chemical and visual processing in autism


Brain-wave data collected during a hearing test routinely given to newborns could help clinicians spot neurodevelopmental disorders such as autism in early infancy, according to a new Rutgers-led study.

Researchers found that newborns who later received an autism spectrum ) diagnosis had pronounced delays in their brainstem’s responses to sounds. On average, these newborns had a 1.76-millisecond lag – in a system that operates at a microsecond timescale – compared to newborns who developed neurotypically.

These newborns may have difficulty integrating sound with other sensory streams like vision, movement, and pain because of limited access to sound frequency. Furthermore, they may have difficulty communicating socially and learning languages.

The research, published by Proceedings of the National Academy of Sciences (PNAS Nexus) and led by Rutgers psychology professor Elizabeth Torres, suggests a possible approach for developing a universal screening tool for neurodevelopmental disorders with new avenues for targeted personalized treatments.

“With very little effort and cost, we could build a universal screening test to eliminate disparities in infant neurodevelopment and establish normative scales of such a dynamic process,” said Torres, who is also the director of the New Jersey Autism Center of Excellence. “This will give us the ability to measure individual departures from these neurotypical ranges, as early as possible, when the nervous system is rapidly changing and adapting to its environment, and the brain-body circuitry is forming.”

In the study, the researchers examined fluctuations in waveforms — which are often discarded across repetitions — recorded by the Auditory Brainstem Response (ABR) test that assesses hearing. In this test, clinicians play clicks to sleeping babies, whose brain response is recorded using soft electrodes.

“At birth, the brainstem is already critical for survival functions like breathing, swallowing and excreting, but also serves as a conduit to the neocortex, subcortical regions, the cerebellum and the spinal cord, where emergent control and coordination of actions give rise to basic building blocks of social behaviors,” said Torres. “As a result of the extreme plasticity of an infant’s brain, the earlier the therapeutic intervention, the more effective the treatment will be.”

The results may explain differences in language acquisition, sensory processing, and motor control, which are all fundamental to social interactions and communication as the baby grows and matures. It also explains why young autistic children have excess noise in their movements, with repetitions of actions, or “stimming,” and unexpected responses to various sensory stimuli.

In the experiment, the team first standardized the waveforms to remove anatomical differences, such as head circumference, as a source of variability. They then compared waveforms from infants who were later diagnosed with an autism spectrum disorder to a similar number of babies who were not.

The babies who would go on to receive an autism diagnosis showed consistently delayed responses to the clicks and reduced access to sound frequencies.

Torres, who leads the Sensory Motor Integration Lab and the New Jersey Autism Center of Excellence, said by the time those with autism receive their diagnosis in the U.S. and even later abroad, their nervous systems developed compensatory coping mechanisms and circuitry different from neurotypical babies.

Researchers can catch these differences early enough to support the system to process sensory signals within the ranges and timescales that will coincide with those of neurotypical individuals, thus enabling information processing and communication between two systems.

“Research shows that the so-called “repetitive, ritualistic behaviors” are an adaptation of a system that is operating on different hardware and nevertheless, attempting to communicate with us,” said Torres. “Our results call us to rethink what autism really is.”