Progress on Brain Scans

A release from UC San Diego:

Using functional magnetic resonance imaging (fMRI), University of California, San Diego School of Medicine researchers say it may be possible to predict future language development outcomes in toddlers with autistic spectrum disorder (ASD), even before they’ve been formally diagnosed with the condition.

 The findings are published in the April 9 online issue of the journal Neuron.

A major challenge of ASD diagnosis and treatment is that the neurological condition – which affects 1 in 68 children in the United States, mostly boys – is considerably heterogeneous. Early symptoms differ between each ASD toddler, as does progression of the condition. No uniform clinical phenotype exists, in part because the underlying causes for different subtypes of autism are diverse and not well-understood.

“There is no better example than early language development,” said senior author Eric Courchesne, PhD, professor of neurosciences and co-director of the Autism Center of Excellence at UC San Diego. “Some individuals are minimally verbal throughout life. They display high levels of symptom severity and may have poor clinical outcomes. Others display delayed early language development, but then progressively acquire language skills and have relatively more positive clinical outcomes.”

In other words, said Courchesne, in some children with ASD language improves substantially with age; but in some it may progress too slowly or even diminish. The neurodevelopmental bases for this variability are unknown, he said. Differences in treatment quantity do not fully account for it. But numerous studies have shown that early, accurate diagnoses of ASD can improve treatment benefits in many affected children.

“It’s important to develop more and new biological ways to identify and stratify the ASD population into clinical sub-types so that we can create better, more individualized treatments,” said co-author Karen Pierce, PhD, associate professor of neurosciences and co-director of the Autism Center of Excellence.

In the Neuron paper, Courchesne, first author Michael V. Lombardo, PhD, a senior researcher at the University of Cambridge and assistant professor at the University of Cyprus, Pierce and colleagues describe the first effort to create a process capable of detecting different brain subtypes within ASD that underlie and help explain varying development language trajectories and outcomes. “We wanted to see if patterns of brain activity in response to language can explain and predict how well language skills would develop in a toddler with ASD before that toddler actually began talking,” said Courchesne.

The researchers combined prospective fMRI measurements of neural systems’ response to speech in children at the earliest ages at which risk of ASD can be clinically detected in a general pediatric population (at approximately ages 1-2 years) with comprehensive longitudinal diagnostic and clinical assessments of language skills at 3-4 years of age.

They found that pre-diagnosis fMRI response to speech in ASD toddlers with relatively good language outcomes was highly similar to non-ASD comparison groups with robust responses to language in superior temporal cortices, a region of the brain responsible for processing sounds so that they can be understood as language.

In contrast, ASD toddlers with poor language outcomes had superior temporal cortices that showed diminished or abnormal inactivity to speech.

In sum, the study found entirely different neural substrates at initial clinical detection that precede and underlie later good versus poor language outcome in autism. These findings, said researchers, will open new avenues of progress towards identifying the causes and best treatment for these two very different types of autism.

“For the first time, our study shows a strong relationship between irregularities in speech-activation in the language-critical superior temporal cortex and actual, real-world language ability in ASD toddlers,” said Lombardo.

The scientists said fMRI imaging also showed that the brains of ASD toddlers with poor language development processed speech differently, including how neural regions governing emotion, memory and motor skills were involved.

“Our work represents one of the first attempts using fMRI to define a neurofunctional biomarker of a subtype in very young ASD toddlers,” said Pierce. “Such subtypes help us understand the differences between persons with ASD. More importantly, they can help us determine how and why treatments are effective for some, but not all, on the autism spectrum.”

Co-authors include Lisa Eyler, UCSD and Veterans Affairs San Diego Healthcare System; Cindy Carter Barnes, Clelia Ahrens-Barbeau, Stephanie Solso, and Kathleen Campbell, UCSD. Funding for this research came, in part, from National Institute of Mental Health grants P50-MH081755, R01-MH080134 and R01-MH036840, the National Foundation for Autism Research and Jesus College, Cambridge and the British Academy.

A Practical Difficulty in Brain Science

Many posts have discussed brain science and autism.

SFARI reports:

Over the past decade, scores of researchers have used magnetic resonance imaging (MRI) to reveal structural abnormalities in the brains of people with autism. One of the most consistent findings is that thecortex is larger than normal during childhood and shrinks earlier than normal during adolescence.

A new study calls these findings into question. The study, published 10 December in Neuroimage, shows that head movement during structural MRI causes certain regions of the cortex to appear smaller and thinner than they actually are.
...
It’s too early to say whether head movements skewed the results of studies that reported structural abnormalities in the brains of people with autism. But the new findings underscore the importance of safeguarding against head motion during brain imaging. This is especially important for studies involving people with autism, who are known to move their heads in MRI scanners more than controls do.

Brains

From Autism Speaks:

Autism Speaks, the Simons Foundation and the Autism Science Foundation have launched “It Takes Brains,” the new donor registration site for Autism BrainNet.

Autism Speaks Chief Science Officer Rob Ring joined Autism BrainNet Director David Amaral and the Simons Foundation’s Marta Bennedetti in making the announcement at the annual Stakeholders Luncheon at the International Meeting for Autism Research (IMFAR), in Atlanta today.

A year ago, the Simons Foundation and Autism Speaks announced their collaboration in establishing Autism BrainNet to collect, store and distribute the precious brain tissue needed to advance scientific understanding and treatment of autism. The new foundation grew out of the Autism Speaks Autism Tissue Program.

As Autism BrainNet’s outreach program, the “It Takes Brains” website encourages families affected by the disorder to register as future donors.

“I would encourage any family to register to be donors,” says BrainNet family participant Valerie Hund, of Livermore, California. “Although we could not have anticipated losing our son to a seizure, for us, in that moment, we gave back and did something that felt right. So now Grayson can be a pioneer in helping make this next quantum leap in research. Out of something bad, something good came about.”

A severe shortage of human brain tissue has hindered the pace of autism research. At the same time, these precious donations have led to recent breakthroughs.

For instance, research has revealed structural differences between brain tissue from individuals affected by autism and typically developed brains. Other studies have highlighted differences in the numbers and sizes of brain nerve cells, or neurons. Still other research has picked up signs of increased inflammation in brain tissue from individuals affected by autism. In addition, studies have uncovered differences in how genes are expressed inside their brain cells.

However, researchers have not been able to adequately confirm these findings – in part due to the long-standing shortage of donations.

Brain Differences

New research suggests that autism may be different in men and women, and that autism may be different from Asperger's.

The Los Angeles Times reports [h/t JM]:

Do women who are on the autism spectrum have brains that are more “masculine”?

A team of researchers at Cambridge University's Autism Research Center has found striking similarities between the structural anomalies found in the brains of women with autism spectrum disorder and neurobiological characteristics known to be different between males and females in general.

The results, published online Thursday in the review Brain, partially confirm aspects of an “extreme male brain” theory of autism put forth by Cambridge neuroscientist Simon Baron-Cohen and his colleagues. But other results of the study appeared to shake the theory -- scans of the brains of men with autism didn’t exhibit a discernible “extreme” of masculine architecture.

At the least, the study adds significant evidence that there are fundamental differences between the brains of women with autism and those of their male counterparts, and highlights the need to include more women in studies. Although males are disproportionately represented in the population of autistics by a ratio of 2:1 or 3:1, the gender disparity in research samples hovers closer to 8:1, according to the study authors.

The Huffington Post reports on an EEG study showing Asperger kids have brain connectivity patterns different from those of autistic kids.

"We looked at a group of 26 children with Asperger's, to see whether measures of brain connectivity would indicate they're part of autism group, or they stood separately," said study researcher Dr. Frank Duffy, a neurologist at Boston's Children Hospital. The study also included more than 400 children with autism, and about 550 typically-developing children, who served as controls.

At first, the test showed that children with Asperger's and those with autism were similar: both showed weaker connections, compared with typically-developing children, in a region of the brain's left hemisphere called the arcuate fasciculus, which is involved in language.

However, when looking at connectivity between other parts of the brain, the researchers saw differences. Connections between several regions in the left hemisphere were stronger in children with Asperger's than in both children with autism and typically-developing children.
The results suggest the conditions are related, but there are physiological differences in brain connectivity that distinguish children with Asperger's from those with autism, according to the study published Wednesday (July 31) in the journal BMC Medicine.

Diagnosis By Brain Scan? Not Yet.

Previous posts have discussed the potential role of brain scans in diagnosing autism. A release from McLean Hospital:

In a column appearing in the current issue of the journal Nature, McLean Hospital biostatistician Nicholas Lange, ScD, cautions against heralding the use of brain imaging scans to diagnose autism and urges greater focus on conducting large, long-term multicenter studies to identify the biological basis of the disorder.  

"Several studies in the past two years have claimed that brain scans can diagnose autism, but this assertion is deeply flawed," said Lange, an associate professor of Psychiatry and Biostatistics at Harvard Medical School. "To diagnose autism reliably, we need to better understand what goes awry in people with the disorder. Until its solid biological basis is found, any attempt to use brain imaging to diagnose autism will be futile."

While cautioning against current use of brain imaging as a diagnostic tool, he is a strong proponent of using this technology to help scientists better understand autism. Through the use of various brain imaging techniques, including functional magnetic resonance imaging (MRI), positron emission tomography (PET), and volumetric MRI, Lange points out that researchers have made important discoveries related to early brain enlargement in the disorder, how those with autism focus during social interaction and the role of serotonin in someone with autism.

"Brain scans have led to these extremely valuable advances, and, with each discovery, we are getting closer to solving the autism pathology puzzle," said Lange. "What individuals with autism and their parents urgently need is for us to carry out large-scale studies that lead us to find reliable, sensitive and specific biological markers of autism with high predictive value that allow clinicians to identify interventions that will improve the lives of people with the disorder."

Autism and autism spectrum disorder (ASD) are terms regularly used to describe a group of complex disorders of brain development. This spectrum characterized, in varying degrees, by difficulties in social interaction, verbal and nonverbal communication, and repetitive behaviors, whose criteria have been revised in the newly proposed Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The prevalence of ASD in the United States has increased 78 percent in the last decade, with the Centers for Disease Control estimating that one in 88 children has ASD.

More information: "Imaging Autism," doi:10.1038/491S17a Journal reference: Nature Provided by McLean Hospital

Read more at: http://medicalxpress.com/news/2012-11-brain-imaging-autism.html#jCp

Early Diagnosis, Early Intervention

New research has implications for early intervention.  From a release by the Children's Hospital of Philadelphia:

A new study from the Infant Brain Imaging Network, which includes researchers at the Center for Autism Research at The Children's Hospital of Philadelphia(CHOP), found significant differences in brain development starting at age 6 months in high-risk infants who later develop autism, compared to high-risk infants who did not develop autism.

"It's a tremendously exciting finding," said Sarah Paterson, PhD, director of the Infant Neuroimaging Lab at CHOP's Center for Autism Research. "We found that the brains of the children who developed autism were markedly different even prior to the onset of behavioral symptoms of autism. Thus, our findings, while requiring replication, are a very important first step towards identifying a biomarker for autism risk. This would enable specialists to diagnose autism much earlier than what is currently possible through behavioral observations."

The study also suggests that autism does not appear suddenly in young children but instead develops over time during infancy, note the authors. Intensive early intervention has been shown to improve outcomes in children with developmental delays and autism.

"This research raises the possibility that we might be able to intervene even before a child is 6 months old, to blunt or prevent the development of some autism symptoms," said Paterson.

The study was published February 17th in the American Journal of Psychiatry. Its results are the latest from the ongoing Infant Brain Imaging Study (IBIS), which is led at CHOP by Dr. Paterson and Robert Schultz, PhD, who are co-authors on this study.

Media, Autism, and Brain Scans

Following yesterday's post about autism screening, a new story has popped up. From US News HealthDay:

A type of brain imaging that measures the circuitry of brain connections may someday be used to diagnose autism, new research suggests.

Researchers at McLean Hospital in Boston and the University of Utah used MRIs to analyze the microscopic fiber structures that make up the brain circuitry in 30 males aged 8 to 26 with high-functioning autism and 30 males without autism.

...

The study is published in the Dec. 2 online edition of Autism Research.

Dr. Stewart Mostofsky, medical director at the Kennedy Krieger Institute's Center for Autism and Related Disorders, called the study "intriguing." However, it remains to be seen if the test is sensitive enough to distinguish between autism and other developmental conditions that impact the brain.

"This is a very preliminary step and one that will require larger samples of children and a broader range of children with autism and other development disorders, particularly other developmental language disorders," Mostofsky said.

This piece is a good example of cautious reporting. Compare and contrast with the hype in the UK Daily Mail:

MRI scan that can tell you within minutes if your child is autistic

A brain scan which diagnoses autism in children in just ten minutes has been developed by scientists.

It would enable the condition to be detected at a much earlier stage so youngsters could begin therapy and treatment before they started school.

The test, which is almost 95 per cent accurate, uses Magnetic Resonance Imaging (MRI) scanners to show how well the different parts of the brain communicating.

Research News

The New York Times reports (h/t John McNulty):

In the three years since her son Diego was given a diagnosis of autism at age 2, Carmen Aguilar has made countless contributions to research on this perplexing disorder.

She has donated all manner of biological samples and agreed to keep journals of everything she’s eaten, inhaled or rubbed on her skin. Researchers attended the birth of her second son, Emilio, looking on as she pushed, leaving with Tupperware containers full of tissue samples, the placenta and the baby’s first stool.

Now the family is in yet another study, part of an effort by a network of scientists across North America to look for signs of autism as early as 6 months. (Now, the condition cannot be diagnosed reliably before age 2.) And here at the MIND Institute at the University of California Davis Medical Center, researchers are watching babies like Emilio in a pioneering effort to determine whether they can benefit from specific treatments.

So when Emilio did show signs of autism risk at his 6-month evaluation — not making eye contact, not smiling at people, not babbling, showing unusual interest in objects — his parents eagerly accepted an offer to enroll him in a treatment program called Infant Start.

The treatment is based on a daily therapy, the Early Start Denver Model, that is based on games and pretend play. It has been shown in randomized trials to significantly improve I.Q., language and social skills in toddlers with autism, and researchers say it has even greater potential if it can be started earlier.

Time reports:

Too many tight connections in frontal-lobe circuits and too few long-distance links between the frontal lobe and the rest of the brain may cause some of the language, social problems and repetitive behavior seen in autism spectrum disorders, according to a new study published in Science Translational Medicine. The research links a variant of the CNTNAP2 gene to this particular type of rewiring in the brain.

The new findings, which used functional magnetic resonance imaging (fMRI) to measure the types and strength of connections between brain regions, could provide autism experts with some important clues for early intervention and treatment. (More on Time.com: Special Report: Kids and Mental Health)

"I think it is quite a beautiful study," says Kamila Markram, director of the Autism Project at the Brain Mind Institute of the École Polytechnique Fédérale de Lausanne in Switzerland, who was not associated with the current research. "What's new is that it brings the genetic data together with the functional brain activity and that is usually not done. Either people look at gene expression or they look at functional brain activity. To bring them together and relate them to say, 'That particular gene is responsible for the different connection pattern that one observes,' that's a unique research area and that's the beauty of the study."

At The Age of Autism, Katie Wright says:

... I want all autism families to know that the leaders of Department of Defense’s autism research program really get it. They are our allies in the fight for our children, rather than just another obstacle. The DOD strongly believes in stakeholder involvement.

The DoD actually WANTS parents’ opinion regarding their research choices. They INVITE a diverse body of Moms and Dads in sit on their grant committee panels. The DoD ENCOURAGES parents to fully participate in all scientific, clinical and treatment discussions. DoD EMPOWERS each stakeholder as a fully voting members of grant committees. The DoD ASKS families what they think of their previous research work and how they can better respond to the needs of people living with autism NOW.

Autism in the Media: The Case of the Brain Scan

Another in a series of "revolutionary" developments in autism science:

The British National Health Service, however, emphasizes caution:

The study was carried out by researchers from the Institute of Psychiatry at Kings College in London. Funded was provided by the Medical Research Council. The study was published in the (peer-reviewed) Journal of Neuroscience.

The study was widely reported in the media, with most stories relying on a press release and interviews to interpret the scientific data from the study. Few reports focused on the small size of the study or the need for further research on this method. The claim in the Daily Express, that autism can now be detected by a 15-minute brain scan, was incorrect.

....

In particular, it is necessary to clarify that this method can specifically differentiate between ASD and other neuro-developmental conditions. In addition, the implications of such a test for ASD would need careful consideration, including which people would be eligible for the test and whether it should be considered for use in children.

The researchers also note that:

• Differences in scanners may have affected the ADHD classification.
• The variation in accuracy between the right and left hemisphere needs further exploration.
• The classification algorithm was only used on high-functioning adults with ASD, so it is not known whether it would produce the same results in other groups with more severe ASD.
• The small sample size made it impossible to investigate possible brain differences between autism and Asperger’s syndrome.