Presence or absence of early language delay alters anatomy of the brain in autism

A new study led by researchers from the University of Cambridge has found that a common characteristic of autism – language delay in early childhood – leaves a ‘signature’ in the brain. The results are published today (23 September) in the journal Cerebral Cortex.

The researchers studied 80 adult men with autism: 38 who had delayed language onset and 42 who did not. They found that language delay was associated with differences in brain volume in a number of key regions, including the temporal lobe, insula, ventral basal ganglia, which were all smaller in those with language delay; and in brainstem structures, which were larger in those with delayed language onset.

Additionally, they found that current language function is associated with a specific pattern of grey and white matter volume changes in some key brain regions, particularly temporal, frontal and cerebellar structures.

The Cambridge researchers, in collaboration with King’s College London and the University of Oxford, studied participants who were part of the MRC Autism Imaging Multicentre Study (AIMS).

Delayed language onset – defined as when a child’s first meaningful words occur after 24 months of age, or their first phrase occurs after 33 months of age – is seen in a subgroup of children with autism, and is one of the clearest features triggering an assessment for developmental delay in children, including an assessment of autism.

“Although people with autism share many features, they also have a number of key differences,” said Dr Meng-Chuan Lai of the Cambridge Autism Research Centre, and the paper’s lead author. “Language development and ability is one major source of variation within autism. This new study will help us understand the substantial variety within the umbrella category of ‘autism spectrum’. We need to move beyond investigating average differences in individuals with and without autism, and move towards identifying key dimensions of individual differences within the spectrum.”

He added: “This study shows how the brain in men with autism varies based on their early language development and their current language functioning. This suggests there are potentially long-lasting effects of delayed language onset on the brain in autism.”

Last year, the American Psychiatric Association removed Asperger Syndrome (Asperger’s Disorder) as a separate diagnosis from its diagnostic manual (DSM-5), and instead subsumed it within ‘autism spectrum disorder.’ The change was one of many controversial decisions in DSM-5, the main manual for diagnosing psychiatric conditions.

“This new study shows that a key feature of Asperger Syndrome, the absence of language delay, leaves a long lasting neurobiological signature in the brain,” said Professor Simon Baron-Cohen, senior author of the study. “Although we support the view that autism lies on a spectrum, subgroups based on developmental characteristics, such as Asperger Syndrome, warrant further study.”

“It is important to note that we found both differences and shared features in individuals with autism who had or had not experienced language delay,” said Dr Lai. “When asking: ‘Is autism a single spectrum or are there discrete subgroups?’ - the answer may be both.”

Scientists track the rise and fall of brain volume throughout life

We can witness our bodies mature, then gradually grow wrinkled and weaker with age, but it is only recently that scientists have been able to track a similar progression in the nerve bundles of our brains. That tissue increases in volume until around age 40, then slowly shrinks. By the end of our lives the tissue is about the volume of a 7-year-old.

So finds a team of Stanford scientists who used a new magnetic resonance imaging technique to show, for the first time, how human brain tissue changes throughout life. Knowing what’s normal at different ages, doctors can now image a patient’s brain, compare it to this standard curve and be able to tell if a person is out of the normal range, much like the way a growth chart can help identify kids who have fallen below their growth curve. The researchers have already used the technique to identify previously overlooked changes in the brain of people with multiple sclerosis.

"This allows us to look at people who have come into the clinic, compare them to the norm and potentially diagnose or monitor abnormalities due to different diseases or changes due to medications," said Jason Yeatman, a graduate student in psychology and first author on a paper published today in Nature Communications. Aviv Mezer, a research associate, was senior author on the paper. Both collaborated with Brian Wandell, a professor of psychology, and his team.

For decades scientists have been able to image the brain using magnetic resonance imaging (MRI) and detect tumors, brain activity or abnormalities in people with some diseases, but those measurements were all subjective. A scientist measuring some aspect of the brain in one lab couldn’t directly compare findings with someone in another lab. And because no two scans could be compared, there was no way to look at a patient’s image and know whether it fell outside the normal range.

Limitation overcome

"A big problem in MRI is variation between instruments," Mezer said. Last year Mezer and Wandell led an interdisciplinary team to develop a technique that can be used to compare MRI scans quantitatively between labs, described in Nature Medicine. “Now with that method we found a way to measure the underlying tissue and not the instrumental bias. So that means that we can measure 100 subjects here and Jason can measure another 100 in Seattle (where he is now a postdoctoral fellow) and we can put them all in a database for the community.”

The technique the team had developed measures the amount of white matter tissue in the brain. That amount of white matter comes primarily from an insulating covering called myelin that allows nerves to fire most efficiently and is a hallmark of brain maturation, though the white matter can also be composed of other types of cells in the brain.

White matter plays a critical role in brain development and decline, and several diseases including schizophrenia and autism are associated with white matter abnormalities. Despite its importance in normal development and disease, no metric existed for determining whether any person’s white matter fell within a normal range, particularly if the people were imaged on different machines.

Mezer and Yeatman decided to use the newly developed quantitative technique to develop a normal curve for white matter levels throughout life. They imaged 24 regions within the brains of 102 people ages 7 to 85, and from that established a set of curves showing the increase and then eventual decrease in white matter in each of the 24 regions throughout life.

What they found is that the normal curve for brain composition is rainbow-shaped. It starts and ends with roughly the same amount of white matter and peaks between ages 30 and 50. But each of the 24 regions changes a different amount. Some parts of the brain, like those that control movement, are long, flat arcs, staying relatively stable throughout life.

Others, like the areas involved in thinking and learning, are steep arches, maturing dramatically and then falling off quickly. (The group did point out that their samples started at age 7 and a lot of brain development had already occurred.)

Continued collaboration

"Regions of the brain supporting high-level cognitive functions develop longer and have more degradation," Yeatman said. "Understanding how that relates to cognition will be really important and interesting." Yeatman is now a postdoctoral scholar at the University of Washington, and Mezer is now an assistant professor at the Hebrew University of Jerusalem. They plan to continue collaborating with each other and with other members of the Wandell lab, looking at how brain composition correlates with learning and how it could be used to diagnose diseases, learning disabilities or mental health issues.

The group has already shown that they can identify people with multiple sclerosis (MS) as falling outside the normal curve. People with MS develop what are known as lesions – regions in the brain or spinal cord where myelin is missing. In this paper, the team showed that they could identify people with MS as being off the normal curve throughout regions of the brain, including places where there are no visible lesions. This could provide an alternate method of monitoring and diagnosing MS, they say.

Wandell has had a particular interest in studying the changes that happen in the brain as a child learns to read. Until now, if a family brought a child into the clinic with learning disabilities, Wandell and other scientists had no way to diagnose whether the child’s brain was developing normally, or to determine the relationship between learning delays and white matter abnormalities.

"Now that we know what the normal distribution is, when a single person comes in you can ask how their child compares to the normal distribution. That’s where this is headed," said Wandell, who is also the Isaac and Madeline Stein Family professor and a Stanford Bio-X affiliate. Wandell runs the Center for Cognitive and Neurobiological Imaging (CNI), where Mezer and the team developed the MRI technique to quantify white matter, and where the scans for this study were conducted.

The ability to share data among scientists is an issue Wandell has championed at the CNI and has been promoting in his work helping the Stanford Neurosciences Institute plan the computing strategy for their new facility. “Sharing of data and computational methods is critical for scientific progress,” Wandell said. In line with that goal, the new standard curve for white matter is something scientists around the world can use and contribute data to.

Migraine May Permanently Change Brain Structure

Migraine may have long-lasting effects on the brain’s structure, according to a study published in the August 28, 2013, online issue of Neurology®, the medical journal of the American Academy of Neurology.

“Traditionally, migraine has been considered a benign disorder without long-term consequences for the brain,” said study author Messoud Ashina, MD, PhD, with the University of Copenhagen in Denmark. “Our review and meta-analysis study suggests that the disorder may permanently alter brain structure in multiple ways.”

The study found that migraine raised the risk of brain lesions, white matter abnormalities and altered brain volume compared to people without the disorder. The association was even stronger in those with migraine with aura.

For the meta-analysis, researchers reviewed six population-based studies and 13 clinic-based studies to see whether people who experienced migraine or migraine with aura had an increased risk of brain lesions, silent abnormalities or brain volume changes on MRI brain scans compared to those without the conditions.

The results showed that migraine with aura increased the risk of white matter brain lesions by 68 percent and migraine with no aura increased the risk by 34 percent, compared to those without migraine. The risk for infarct-like abnormalities increased by 44 percent for those with migraine with aura compared to those without aura. Brain volume changes were more common in people with migraine and migraine with aura than those with no migraines.

“Migraine affects about 10 to 15 percent of the general population and can cause a substantial personal, occupational and social burden,” said Ashina. “We hope that through more study, we can clarify the association of brain structure changes to attack frequency and length of the disease. We also want to find out how these lesions may influence brain function.”

(Image: Getty images)

Reduced brain volume in kids with low birth-weight tied to academic struggles

An analysis of recent data from magnetic resonance imaging (MRI) of 97 adolescents who were part of study begun with very low birth weight babies born in 1982-1986 in a Cleveland neonatal intensive care unit has tied smaller brain volumes to poor academic achievement.

More than half of the babies that weighed less than 1.66 pounds and more than 30 percent of those less than 3.31 pounds at birth later had academic deficits. (Less than 1.66 pounds is considered extremely low birth weight; less than 3.31 pounds is labeled very low birth weight.) Lower birth weight was associated to smaller brain volumes in some of these children, and smaller brain volume, in turn, was tied to academic deficits.

Researchers also found that 65.6 percent of very low birth weight and 41.2 percent of extremely preterm children had experienced academic achievement similar to normal weight peers.

The research team — led by Caron A.C. Clark, a scientist in the Department of Psychology and Child and Family Center at the University of Oregon — detected an overall reduced volume of mid-brain structures, the caudate and corpus callosum, which are involved in connectivity, executive attention and motor control.

The findings, based a logistic regression analyses of the MRIs done approximately five years ago, were published in the May issue of the journal Neuropsychology. The longitudinal study originally was launched in the 1980s with a grant from the National Institute of Child Health and Human Development (National Institutes of Health, grant HD 26554) to H. Gerry Taylor of Case Western University, who was the senior author and principal investigator on the new paper.

"Our new study shows that pre-term births do not necessarily mean academic difficulties are ahead," Clark said. "We had this group of children that did have academic difficulties, but there were a lot of kids in this data set who didn’t and, in fact, displayed the same trajectories as their normal birth-weight peers."

Academic progress of the 201 original participants had been assessed early in their school years, again four years later and then annually until they were almost 17 years old. “We had the opportunity to explore this very rich data set,” Clark said. “There are very few studies that follow this population of children over time, where their trajectories of growth at school are tracked. We were interested in seeing how development unfolds over time.”

The findings, Clark added, provide new insights but also raise questions such as why some low-birth-weight babies develop normally and others do not? “It is very difficult to pick up which kids will need the most intensive interventions really early, which we know can be really important.”

The findings also provide a snapshot of children of very low birth weights who were born in NICU 30 years ago. Since then, technologies and care have improved, she said, meaning that underweight babies born prematurely today might have an advantage over those followed in the study. However, she added, improving NICUs also are allowing yet smaller babies to survive.

Clark now is exploring these findings for early warning clues that might help drive informed interventions. “Pre-term birth does mean that you are much more likely to experience brain abnormalities that seem to put you at risk for these outcomes,” she said. “They seem to be a pretty strong predictor of poor cognitive development as children age. We really need to find ways to prevent these brain abnormalities and subsequent academic difficulties in these kids who are born so small.”

Single Concussion May Cause Lasting Brain Damage

A single concussion may cause lasting structural damage to the brain, according to a new study published online in the journal Radiology.

"This is the first study that shows brain areas undergo measureable volume loss after concussion," said Yvonne W. Lui, M.D., Neuroradiology section chief and assistant professor of radiology at NYU Langone School of Medicine. "In some patients, there are structural changes to the brain after a single concussive episode."

According to the Centers for Disease Control and Prevention, each year in the U.S., 1.7 million people sustain traumatic brain injuries, resulting from sudden trauma to the brain. Mild traumatic brain injury (MTBI), or concussion, accounts for at least 75 percent of all traumatic brain injuries.

Following a concussion, some patients experience a brief loss of consciousness. Other symptoms include headache, dizziness, memory loss, attention deficit, depression and anxiety. Some of these conditions may persist for months or even years.

Studies show that 10 to 20 percent of MTBI patients continue to experience neurological and psychological symptoms more than one year following trauma. Brain atrophy has long been known to occur after moderate and severe head trauma, but less is known about the lasting effects of a single concussion.

Dr. Lui and colleagues set out to investigate changes in global and regional brain volume in patients one year after MTBI. Twenty-eight MTBI patients (with 19 followed at one year) with post-traumatic symptoms after injury and 22 matched controls (with 12 followed at one year) were enrolled in the study. The researchers used three-dimensional magnetic resonance imaging (MRI) to determine regional gray matter and white matter volumes and correlated these findings with other clinical and cognitive measurements.

The researchers found that at one year after concussion, there was measurable global and regional brain atrophy in the MTBI patients. These findings show that brain atrophy is not exclusive to more severe brain injuries but can occur after a single concussion.

"This study confirms what we have long suspected," Dr. Lui said. "After MTBI, there is true structural injury to the brain, even though we don’t see much on routine clinical imaging. This means that patients who are symptomatic in the long-term after a concussion may have a biologic underpinning of their symptoms."

Certain brain regions showed a significant decrease in regional volume in patients with MTBI over the first year after injury, compared to controls. These volume changes correlated with cognitive changes in memory, attention and anxiety.

"Two of the brain regions affected were the anterior cingulate and the precuneal region," Dr. Lui said. "The anterior cingulate has been implicated in mood disorders including depression, and the precuneal region has a lot of different connections to areas of the brain responsible for executive function or higher order thinking."

According to Dr. Lui, researchers are still investigating the long-term effects of concussion, and she advises caution in generalizing the results of this study to any particular individual.

"It is important for patients who have had a concussion to be evaluated by a physician," she said. "If patients continue to have symptoms after concussion, they should follow-up with their physician before engaging in high-risk activities such as contact sports."