Shedding new light on learning disorders

A Michigan State University researcher has discovered the first anatomical evidence that the brains of children with a nonverbal learning disability – long considered a “pseudo” diagnosis – may develop differently than the brains of other children.

The finding, published in Child Neuropsychology, could ultimately help educators and clinicians better distinguish between – and treat – children with a nonverbal learning disability, or NLVD, and those with Asperger’s, or high functioning autism, which is often confused with NLVD.

“Children with nonverbal learning disabilities and Asperger’s can look very similar, but they can have very different reasons for why they behave the way they do,” said Jodene Fine, assistant professor of school psychology in MSU’s College of Education.

Understanding the biological differences in children with learning and behavioral challenges could help lead to more appropriate intervention strategies.

Children with nonverbal learning disability tend to have normal language skills but below average math skills and difficulty solving visual puzzles. Because many of these kids also show difficulty understanding social cues, some experts have argued that NVLD is related to high functioning autism – which this latest study suggests may not be so.

Fine and Kayla Musielak, an MSU doctoral student in school psychology, studied about 150 children ages 8 to 18. Using MRI scans of the participants’ brains, the researchers found that the children diagnosed with NVLD had smaller spleniums than children with other learning disorders such as Asperger’s and ADHD, and children who had no learning disorders.

The splenium is part of the corpus callosum, a thick band of fibers in the brain that connects the left and right hemispheres and facilitates communication between the two sides. Interestingly, this posterior part of the corpus callosum serves the areas of the brain related to visual and spatial functioning.

In a second part of the study, the participants’ brain activity was analyzed after they were shown videos in an MRI that portrayed both positive and negative examples of social interaction. (A typical example of a positive event was a child opening a desired birthday present with friend; a negative event included a child being teased by other children.)

The researchers found that the brains of children with nonverbal learning disability responded differently to the social interactions than the brains of children with high functioning autism, or HFA, suggesting the neural pathways that underlie those behaviors may be different.

“So what we have is evidence of a structural difference in the brains of children with NLVD and HFA, as well as evidence of a functional difference in the way their brains behave when they are presented with stimuli,” Fine said.

While more research is needed to better understand how nonverbal learning disability fits into the family of learning disorders, Fine said her findings present “an interesting piece of the puzzle.”

“I would say at this point we still don’t have enough evidence to say NVLD is a distinct diagnosis, but I do think our research supports the idea that it might be,” she said.

Connections in the brains of young children strengthen during sleep

While young children sleep, connections between the left and the right hemispheres of their brain strengthen, which may help brain functions mature, according to a new study by the University of Colorado Boulder.

The research team—led by Salome Kurth, a postdoctoral researcher, and Monique LeBourgeois, assistant professor in integrative physiology—used electroencephalograms, or EEGs, to measure the brain activity of eight sleeping children multiple times at the ages of 2, 3 and 5 years.

“Interestingly, during a night of sleep, connections weakened within hemispheres but strengthened between hemispheres,” Kurth said.

Scientists have known that the brain changes drastically during early childhood: New connections are formed, others are removed and a fatty layer called “myelin” forms around nerve fibers in the brain. The growth of myelin strengthens the connections by speeding up the transfer of information.

Maturation of nerve fibers leads to improvement in skills such as language, attention and impulse control. But it is still not clear what role sleep plays in the development of such brain connections.

In the new study, appearing online in the journal Brain Sciences, the researchers looked at differences in brain activity during sleep as the children got older and differences in brain activity of each child over a night’s sleep. They found that connections in the brain generally became stronger during sleep as the children aged. They also found that the strength of the connections between the left and right hemispheres increased by as much as 20 percent over a night’s sleep.

“There are strong indications that sleep and brain maturation are closely related, but at this time, it is not known how sleep leads to changes in brain structure,” Kurth said.

Future studies will be aimed at determining how sleep disruption during childhood may affect brain development and behavior.

“I believe inadequate sleep in childhood may affect the maturation of the brain related to the emergence of developmental or mood disorders,” Kurth said.

Researchers Discover Idling Brain Activity in Severely Brain Injured Patients Who “Wake Up” After Using a Sleep Drug

George Melendez has been called a medical miracle. After a near drowning deprived his brain of oxygen, Melendez remained in a fitful, minimally conscious state until his mother, in 2002, decided to give him the sleep aid drug Ambien to quiet his moaning and writhing. The next thing she knew, her son was quietly looking at her and trying to talk. He has been using the drug ever since to maintain awareness, but no one could understand why Ambien led to such an awakening.

Now, a team of scientists led by Weill Cornell Medical College has discovered a signature of brain activity in Melendez and two other similarly “awakened” patients they say explain why he and others regain some consciousness after using Ambien or other drugs or treatments. The pattern of activity, reported Nov. 19 in the journal eLife, was identified by analyzing the common electroencephalography (EEG) test, which tracks brain waves.

"We found a surprisingly consistent picture of electrical activity in all three patients before they receive the drug. Most interesting is that their specific pattern of activity suggests a particular process occurring in the brain cells of the cerebral cortex and also supports the role of a crucial brain circuit," says the study’s senior investigator, Dr. Nicholas Schiff, the Jerold B. Katz Professor of Neurology and Neuroscience and professor of public health at Weill Cornell. "These findings may help predict other patients who might similarly harbor reserve capacity, whether they are able to respond to Ambien or other approaches." Dr. Schiff is also on the faculty of the Feil Family Brain and Mind Research Institute at Weill Cornell and is a neurologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

"We are focused on finding ways to identify patients who have a functional reserve of cognitive capacities that can be rescued and how to achieve this result," Dr. Schiff adds. "These findings give us a very important lead to follow, and we will now rigorously test their implications in other patients."

Although it is not precisely known how many Americans are diagnosed as severely brain injured with disorders of consciousness, by one estimate there are nearly 300,000 patients trapped in a minimally conscious state who may retain some awareness, according to Dr. Schiff.

Riding a Wave of Excitation

The three patients in the study suffered brain damage in different ways. One fell and the other had a brain aneurysm that led to multiple strokes. Melendez was in a car accident that led to his nearly drowning. All three patients — two men and a woman — become aware when Ambien was used, a rare response that has been documented in fewer than 15 brain-injured patients.

The research team, which included scientists from Memorial Sloan-Kettering Cancer Center, Boston University School of Medicine, and the University Hospital of Liège in Belgium, used EEG to measure electrical activity in the patients’ brains before and after they were given the drug.

Although each patient’s brain was damaged in different ways, all showed the same unique features of low frequency waves in their EEG readings. These low frequency oscillations are most prominent over the frontal cortex, a region strongly dependent for its activity on other brain structures, particularly the central thalamus and the striatum, which together support short-term memory, reward, motivation, attention, alertness and sleep, among other functions.

In this setting of an idling brain, the investigators propose that Ambien works like any anesthesia drug, in that it briefly triggers a fast wave of excitation in brain cells before producing sleep — a phenomenon known as paradoxical excitation. Instead of going on to produce sedation and sleep, as it does in healthy people who use the drug, zolpidem further activates the brain after it’s affected the idling cells, allowing the patients to become more awake than at baseline. “What we think is happening in these patients is that the initial excitation produced by Ambien turns on a specific circuit. The drug creates the opportunity for the brain to effectively catch a ride on this initial wave of excitation, and turn itself back on,” Dr. Schiff says.

This proposed “mesocircuit” links the cortical regions of the brain to the central thalamus and striatum. Neurons in the central thalamus are highly connected to other parts of the brain, “so damage in one part of the brain or another will affect the thalamus, which is key to consciousness,” Dr. Schiff says. Neurons in the striatum “will only fire if there is a lot of electrical input coming to them quickly,” he says.

"We believe the switch that Ambien turns on is at the level of the joint connections between these three brain structures," Dr. Schiff says.

The pattern of brain activity seen in the EEG on Ambien was also the same in all the patients in the study. But the circuit turns off again when the effects of the drug diminish. Using the drug regularly at mealtimes, Melendez can speak fluently, and read and write simple phrases. His tremors and spasticity are significantly reduced on Ambien and he can use objects, such as a spoon, and is alert and can communicate. The first patient in the study can reliably move from minimally conscious to “the mid-range of what is called a confusional state — a more alert status, but not full consciousness,” Dr. Schiff says. “Use of Ambien offers a step in the right direction, but certainly not a cure.”

Different Ways to Kick-Start the Brain

The resting EEG pattern the researchers saw in the patients indicates they have a “recruitable reserve” of function in these critical brain areas that Ambien can harness to turn the brain on, even if only temporarily. “The idea is that hopefully we can screen other patients with EEG to find out if they also have such a reserve,” Dr. Schiff says.

And while some of these patients may not respond to Ambien — as the drug works at a very specific brain receptor and individuals can vary considerably in having enough of it in the key components of the proposed circuit — other drugs may target the same structures and potentially produce similar effects, he says. For example, two drugs (amantadine and L-Dopa) that provide extra dopamine, a brain chemical that fuels the part of the brain damaged in the study’s patients, have been shown to have similar effects on restoring function in patients with severe brain injuries, as has electrical brain stimulation of the central thalamus.

"Now that we have uncovered important insight into fundamental mechanisms underlying the dramatic and rare response of some severely brain-injured patients to Ambien, we hope to systematically explore ways to achieve such kick-starts in other patients — that is our goal," Dr. Schiff says.

(Image credit)

People with highly superior powers of recall also vulnerable to false memories

People who can accurately remember details of their daily lives going back decades are as susceptible as everyone else to forming fake memories, UC Irvine psychologists and neurobiologists have found.

In a series of tests to determine how false information can manipulate memory formation, the researchers discovered that subjects with highly superior autobiographical memory logged scores similar to those of a control group of subjects with average memory.

“Finding susceptibility to false memories even in people with very strong memory could be important for dissemination to people who are not memory experts. For example, it could help communicate how widespread our basic susceptibility to memory distortions is,” said Lawrence Patihis, a graduate student in psychology & social behavior at UC Irvine. “This dissemination could help prevent false memories in the legal and clinical psychology fields, where contamination of memory has had particularly important consequences in the past.”

Patihis works in the research group of world-renowned psychologist Elizabeth Loftus, who pioneered the study of false memories and their implications.

Persons with highly superior autobiographical memory (HSAM, also known as hyperthymesia) – which was first identified in 2006 by scientists at UC Irvine’s Center for the Neurobiology of Learning & Memory – have the astounding ability to remember even trivial details from their distant past. This includes recalling daily activities of their life since mid-childhood with almost 100 percent accuracy.

The lead researcher on the study, Patihis believes it’s the first effort to test malleable reconstructive memory in HSAM individuals.

Working with neurobiology & behavior graduate student Aurora LePort, Patihis asked 20 people with superior memory and 38 people with average memory to do word association exercises, recall details of photographs depicting a crime, and discuss their recollections of video footage of the United Flight 93 crash on 9/11. (Such footage does not exist.) These tasks incorporated misinformation in an attempt to manipulate what the subjects thought they had remembered.

“While they really do have super-autobiographical memory, it can be as malleable as anybody else’s, depending on whether misinformation was introduced and how it was processed,” Patihis said. “It’s a fascinating paradox. In the absence of misinformation, they have what appears to be almost perfect, detailed autobiographical memory, but they are vulnerable to distortions, as anyone else is.”

He noted that there are still many mysteries about people with highly superior autobiographical memory that need further investigation. LePort, for instance, is studying forgetting curves (which involve how many autobiographical details people can remember from one day ago, one week ago, one month ago, etc., and how the number of details decreases over time) in both HSAM and control participants and will employ functional MRI to better understand the phenomenon.

“What I love about the study is how it communicates something that memory distortion researchers have suspected for some time: that perhaps no one is immune to memory distortion,” Patihis said. “It will probably make some nonexperts realize, finally, that if even memory prodigies are susceptible, then they probably are too. This teachable moment is almost as important as the scientific merit of the study. It could help educate people – including those who deal with memory evidence, such as clinical psychologists and legal professionals – about false memories.”

The study appears this week in the early online version of Proceedings of the National Academy of Sciences.

iPads help late-speaking children with autism develop language

The iPad you use to check email, watch episodes of Mad Men and play Words with Friends may hold the key to enabling children with autism spectrum disorders to express themselves through speech. New research indicates that children with autism who are minimally verbal can learn to speak later than previously thought, and iPads are playing an increasing role in making that happen, according to Ann Kaiser, a researcher at Vanderbilt Peabody College of education and human development.

In a study funded by Autism Speaks, Kaiser found that using speech-generating devices to encourage children ages 5 to 8 to develop speaking skills resulted in the subjects developing considerably more spoken words compared to other interventions. All of the children in the study learned new spoken words and several learned to produce short sentences as they moved through the training.

“For some parents, it was the first time they’d been able to converse with their children,” said Kaiser, Susan W. Gray Professor of Education and Human Development. “With the onset of iPads, that kind of communication may become possible for greater numbers of children with autism and their families.”

Augmentative and alternative communication devices—which employ symbols, gestures, pictures and speech output—have been used for decades by people who have difficulty speaking. Now, with the availability of apps that emulate those devices, the iPad offers a more accessible, cheaper and more user-friendly way to help minimally verbal children with autism to communicate. And, the iPad is far less stigmatizing for young people with autism who rely on them for communicating with fellow students, teachers and friends.

The reason speech-generating devices like the iPad are effective in promoting language development is simple. “When we say a word it sounds a little different every time, and words blend together and take on slightly different acoustic characteristics in different contexts,” Kaiser explained. “Every time the iPad says a word, it sounds exactly the same, which is important for children with autism, who generally need things to be as consistent as possible.”

As many as a third of children with autism have mastery of only a few words by the time they are school age. Previously, researchers thought that if children with autism had not begun to speak by age 5 or 6, they were unlikely to acquire spoken language. But Kaiser is encouraged by study results and believes that her iPad studies may help change that notion.

Building on findings from this research, Kaiser has begun a new five-year long study supported by the National Institutes of Health’s Autism Centers of Excellence with colleagues at UCLA, University of Rochester, and Cornell Weill Medical School. She and a team of researchers and therapists at the four sites are using iPads in two contrasting interventions (direct-teaching and naturalistic-teaching) to evaluate the effectiveness of the two communication interventions for children who have autism and use minimal spoken language.

In the direct-teaching approach, children are taught prerequisite skills for communication (such as matching objects, motor imitation and verbal imitation) and basic communication skills (such as requesting objects) in a massed trial format. For example, an adult partner may present five to 10 consecutive opportunities for a child to use the iPad to request preferred objects. During these opportunities, the child is prompted to use the iPad to request and may receive physical assistance if he cannot use the iPad independently.

In the naturalistic-teaching approach, the adult models the use of the iPad during play and conversation. She also teaches turn-taking, use of gestures to communicate, play with objects and social attention to partners during the play. She provides a limited number of prompts to use the iPad to make choices, to comment or make new requests.

In both approaches, children touch the symbols on the screen, listen to the device repeat the words, and sometimes say the words themselves. They are encouraged to use both words and the iPad to communicate, and the adult therapist uses both modes of communication throughout the instructional sessions.

Results from the Autism Speaks study will be available in Spring 2014; the NIH study will continue through Spring 2017; and more information can be found at Kidtalk.org.