Validating maps of the brain’s resting state

Kick back and shut your eyes. Now stop thinking.

You have just put your brain into what neuroscientists call its resting state. What the brain is doing when an individual is not focused on the outside world has become the focus of considerable research in recent years. One of the potential benefits of these studies could be definitive diagnoses of mental health disorders ranging from bipolar to post-traumatic stress disorders.

A team of psychologists and imaging scientists at Vanderbilt has collaborated on a study that provides important corroboration of the validity of recent research examining the relationship of functional magnetic resonance imaging or fMRI maps of the brain’s resting state networks with it’s underlying anatomical and neurological structure. The study is published in the June 19 issue of the journal Neuron.

“Previous studies have suggested that resting state connectivity shown in brain scans is anchored by anatomical connectivity,” said co-senior author Anna Roe, professor of psychology at Vanderbilt. “But our study has confirmed this relationship at the single neuron level for the first time.”

For the last decade, neuroscientists have been using the non-invasive brain-mapping technique fMRI to examine activity patterns in human and animal brains in the resting state in order to figure out how different parts of the brain are connected and to identify the changes that occur in neurological and psychiatric diseases. For example, there are indications that Alzheimer’s may be associated with decreased connectivity; depression with increased connectivity; epilepsy with disruptions in connectivity and Parkinson’s with alterations in connectivity.

The new findings from Vanderbilt are important because fMRI doesn’t measure brain activity directly. It does so by measuring changes in blood-oxygen levels in different areas. The technique relies on the observation that when activity in an area of the brain increases, blood-oxygen levels in that region rise, which modulates the MRI signal. Neuroscientists have taken this a step further by assuming that different areas in the brain are connected if they show synchronized variations while the brain is in a resting state.

“This is an important validation,” said co-senior author John Gore, director of the Institute of Imaging Science at Vanderbilt and Hertha Ramsey Cress University Professor of Radiology and Radiological Sciences and Biomedical Engineering. “There has always been a sense of unease that we might be interpreting something incorrectly but this gives us confidence that resting state variations can be interpreted in a meaningful way and encourages us to continue the research we have been doing for a number of years. Resting state fMRI provides a uniquely powerful, non-invasive technology to look at the circuits in the human brain.”

To examine the relationship between fMRI scans, patterns of neuronal activity and anatomical structure of the brain, the researchers examined the region of the parietal lobe of squirrel monkeys devoted to monitoring touch sensations. Specifically, they looked at an area linked to the hand that consists of a series of adjacent areas each devoted to a different finger.

Using one of the strongest MRI machines available, with a field strength three to six times that of typical clinical scanners, the researchers produced brain scans that resolved millimeter-scale networks for the first time.

To compare these patterns to the actual electrical activity in the brains, the researchers inserted electrodes capable of recording the firing patterns of individual neurons. In addition, they used optical techniques to trace the anatomical connections between the neurons throughout the region.

“With all three techniques, we found the same pattern of connectivity. Connections coming from other areas in the brain tend to link to individual digits while connections that originate within the area tend to link to multiple digits,” said Roe. “Our results demonstrate that fMRI images of the resting state brain accurately reflect the brain’s anatomical and functional connectivity down to an extremely fine scale.”

It’s the way you tell em’: Study discovers how the brain controls accents and impersonations

A study, led by Royal Holloway University researcher Carolyn McGettigan, has identified the brain regions and interactions involved in impersonations and accents.

Using an fMRI scanner, the team asked participants, all non-professional impressionists, to repeatedly recite the opening lines of a familiar nursery rhyme either with their normal voice, by impersonating individuals, or by impersonating regional and foreign accents of English.

They found that when a voice is deliberately changed, it brings the left anterior insula and inferior frontal gyrus (LIFG) of the brain into play. The researchers also discovered that when comparing impersonations against accents, areas in the posterior superior temporal/inferior parietal cortex and in the right middle/anterior superior temporal sulcus showed greater responses.

“The voice is a powerful channel for the expression of our identity – it conveys information such as gender, age and place of birth, but crucially, it also expresses who we want to be,” said lead author Carolyn McGettigan from the Department of Psychology at Royal Holloway.

“Consider the difference between talking to a friend on the phone, talking to a police officer who’s cautioning you for parking violation, or speaking to a young infant. While the words we use might be different across these settings, another dramatic difference is the tone and style with which we deliver the words we say. We wanted to find out more about this process and how the brain controls it.”

While past work has found that listening to voices activates regions of the temporal lobe of the brain, no research had explored the brain regions involved in controlling vocal identity before this study.

“Our aim is to find out more about how the brain controls this very flexible communicative tool, which could potentially lead to new treatments for those looking to recover their own vocal identity following brain injury or a stroke, ” said Carolyn.

Fiber-optic pen helps see inside brains of children with learning disabilities

For less than $100, University of Washington researchers have designed a computer-interfaced drawing pad that helps scientists see inside the brains of children with learning disabilities while they read and write.

The device and research using it to study the brain patterns of children will be presented June 18 at the Organization for Human Brain Mapping meeting in Seattle. A paper describing the tool, developed by the UW’s Center on Human Development and Disability, was published this spring in Sensors, an online open-access journal. “Scientists needed a tool that allows them to see in real time what a person is writing while the scanning is going on in the brain,” said Thomas Lewis, director of the center’s Instrument Development Laboratory. “We knew that fiber optics were an appropriate tool. The question was, how can you use a fiber-optic device to track handwriting?”

To create the system, Lewis and fellow engineers Frederick Reitz and Kelvin Wu hollowed out a ballpoint pen and inserted two optical fibers that connect to a light-tight box in an adjacent control room where the pen’s movement is recorded. They also created a simple wooden square pad to hold a piece of paper printed with continuously varying color gradients. The custom pen and pad allow researchers to record handwriting during functional magnetic resonance imaging, or fMRI, to assess behavior and brain function at the same time.Other researchers have developed fMRI-compatible writing devices, but “I think it does something similar for a tenth of the cost,” Reitz said of the UW system. By using supplies already found in most labs (such as a computer), the rest of the supplies – pen, fiber optics, wooden pad and printed paper – cost less than $100.The device connects to a computer with software that records every aspect of the handwriting, from stroke order to speed, hesitations and liftoffs. Understanding how these physical patterns correlate with a child’s brain patterns can help scientists understand the neural connections involved.

Researchers studied 11- and 14-year-olds with either dyslexia or dysgraphia, a handwriting and letter-processing disorder, as well as children without learning disabilities. Subjects looked at printed directions on a screen while their heads were inside the fMRI scanner. The pen and pad were on a foam pad on their laps.

Subjects were given four-minute blocks of reading and writing tasks. Then they were asked to simply think about writing an essay (they later wrote the essay when not using the fMRI). Just thinking about writing caused many of the same brain responses as actual writing would.

“If you picture yourself writing a letter, there’s a part of the brain that lights up as if you’re writing the letter,” said Todd Richards, professor of radiology and principal investigator of the UW Integrated Brain Imaging Center. “When you imagine yourself writing, it’s almost as if you’re actually writing, minus the motion problems.”

Richards and his staff are just starting to analyze the data they’ve collected from about three dozen subjects, but they have already found some surprising results.

“There are certain centers and neural pathways that we didn’t necessarily expect” to be activated, Richards said. “There are language pathways that are very well known. Then there are other motor pathways that allow you to move your hands. But how it all connects to the hand and motion is still being understood.”

Besides learning disorders, the inexpensive pen and pad also could help researchers study diseases in adults, especially conditions that cause motor control problems, such as stroke, multiple sclerosis and Parkinson’s disease.

“There are several diseases where you cannot move your hand in a smooth way or you’re completely paralyzed,” Richards said. “The beauty is it’s all getting recorded with every stroke, and this device would help us to study these neurological diseases.”

Not all reading disabilities are dyslexia

A common reading disorder goes undiagnosed until it becomes problematic, according to the results of five years of study by researchers at Vanderbilt’s Peabody College of education and human development in collaboration with the Kennedy Krieger Institute/Johns Hopkins School of Medicine. Results of the study were recently published online by the National Institutes of Health.

Dyslexia, a reading disorder in which a child confuses letters and struggles with sounding out words, has been the focus of much reading research.

But that’s not the case with the lesser known disorder Specific Reading Comprehension Deficits or S-RCD, in which a child reads successfully but does not sufficiently comprehend the meaning of the words, according to lead investigator Laurie Cutting, Patricia and Rodes Hart Chair at Peabody.

“S-RCD is like this: I can read Spanish, because I know what sounds the letters make and how the words are pronounced, but I couldn’t tell you what the words actually mean,” Cutting said. “When a child is a good reader, it’s assumed their comprehension is on track. But 3 to 10 percent of those children don’t understand most of what they’re reading. By the time the problem is recognized, often closer to third or fourth grade, the disorder is disrupting their learning process.”

Researchers have been able to pinpoint brain activity and understand its role in dyslexia, but no functional magnetic resonance imaging or fMRI studies, until now, have examined the neurobiological profile of those who exhibit poor reading comprehension despite intact word-level abilities.

Neuroimaging of children showed that the brain function of those with S-RCD while reading is quite different and distinct from those with dyslexia. Those with dyslexia exhibited abnormalities in a specific region in the occipital-temporal cortex, a part of the brain that is associated with successfully recognizing words on a page.

But those with S-RCD did not show abnormalities in this region, instead showing specific abnormalities in regions typically associated with memory.

“It may be that these individuals have a whole different neurobiological signature associated with how they read that is not efficient for supporting comprehension,” Cutting said. “We want to understand the different systems that support reading and see which ones help different types of difficulties, and how we can target the cognitive systems that support those skills.”

The study, an ongoing 10-year effort supported by National Institutes of Health grant No. M01-RR000052, has enrolled more than 300 children to date.

Voices may not trigger brain’s reward centers in children with autism

In autism, brain regions tailored to respond to voices are poorly connected to reward-processing circuits, according to a new study by scientists at the Stanford University School of Medicine.

The research could help explain why children with autism struggle to grasp the social and emotional aspects of human speech. “Weak brain connectivity may impede children with autism from experiencing speech as pleasurable,” said Vinod Menon, PhD, senior author of the study, published online June 17 in Proceedings of the National Academy of Sciences. Menon is a professor of psychiatry and behavioral sciences at Stanford and a member of the Child Health Research Institute at Lucile Packard Children’s Hospital.

"The human voice is a very important sound; it not only conveys meaning but also provides critical emotional information to a child," said Daniel Abrams, PhD, a postdoctoral scholar in psychiatry and behavioral sciences who was the study’s lead author. Insensitivity to the human voice is a hallmark of autism, Abrams said, adding, "We are the first to show that this insensitivity may originate from impaired reward circuitry in the brain."

The study focused on children with a high-functioning form of autism. They had IQ scores in the normal range and could speak and read, but had difficulty holding a back-and-forth conversation or understanding emotional cues in another person’s voice.

The scientists compared functional magnetic resonance imaging brain scans from 20 of these children with scans from 19 typically developing children, paying particular attention to a portion of the brain that responds selectively to the sound of human voices. Prior research has shown that adults with autism had low voice-selective cortex activity in response to speech. But until this study by Menon and his colleagues, no one had looked at connections between the voice-selective cortex and other brain regions in individuals with autism.

The new study found that in children with a high-functioning form of autism, the voice-selective cortex on the left side of the brain was weakly connected to the nucleus accumbens and the ventral tegmental area — brain structures that release dopamine in response to rewards. The voice-selective cortex on the right side of the brain, which specializes in detecting vocal cues such as intonation and pitch, was weakly connected to the amygdala, which processes emotional cues.

The weaker these connections in children with autism, the worse their communication deficits, the study showed. The researchers were able to predict the children’s scores on the verbal portion of a standard test of autism severity by looking at the degree of impairment in these brain connections.

The findings may help to validate some autism therapies already in use, said co-author Jennifer Phillips, PhD, a clinical associate professor of psychiatry and behavioral sciences at Stanford who also treats children with autism at Packard Children’s. For instance, pivotal-response training aims to increase social use of language in children who can speak some words but who usually do not talk to others.

"Pivotal-response training goes after ways to naturally motivate kids to start using language and other forms of social interaction," Phillips said. Future studies could test whether brain connections leading from voice to reward centers are strengthened by autism therapies, she added.

The findings also help resolve a long-standing debate about why individuals with autism show less-than-normal interest in human voices. The team investigated two competing theories to explain the phenomenon: that individuals with autism have a deficit in their social motivation, or, alternatively, that they have sensory-processing deficits which impair their ability to fully hear human voices. The new study found normal connections between voice-selective cortex and primary auditory brain regions in children with high-functioning autism, suggesting that these children do not have sensory-processing deficits.

The next steps for researchers include studying the consequences of the weak voice-to-reward circuit in autism. “It is likely that children with autism don’t attend to voices because they are not rewarding or emotionally interesting, impacting the development of their language and social communication skills,” Menon said. “We have discovered an aberrant brain circuit underlying a core deficit in autism; our findings may aid the development of new treatments for this disorder.”

(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.”

Evidence from a quiet MRI: Breastfeeding benefits babies’ brains

A study using brain images from “quiet” MRI machines adds to the growing body of evidence that breastfeeding improves brain development in infants. Breastfeeding alone produced better brain development than a combination of breastfeeding and formula, which produced better development than formula alone.

A new study by researchers from Brown University finds more evidence that breastfeeding is good for babies’ brains.

The study made use of specialized, baby-friendly magnetic resonance imaging (MRI) to look at the brain growth in a sample of children under the age of 4. The research found that by age 2, babies who had been breastfed exclusively for at least three months had enhanced development in key parts of the brain compared to children who were fed formula exclusively or who were fed a combination of formula and breastmilk. The extra growth was most pronounced in parts of the brain associated with language, emotional function, and cognition, the research showed.

This isn’t the first study to suggest that breastfeeding aids babies’ brain development. Behavioral studies have previously associated breastfeeding with better cognitive outcomes in older adolescents and adults. But this is the first imaging study that looked for differences associated with breastfeeding in the brains of very young and healthy children, said Sean Deoni, assistant professor of engineering at Brown and the study’s lead author.

“We wanted to see how early these changes in brain development actually occur,” Deoni said. “We show that they’re there almost right off the bat.”

The findings are in press in the journal NeuroImage and available now online.

Deoni leads Brown’s Advanced Baby Imaging Lab. He and his colleagues use quiet MRI machines that image babies’ brains as they sleep. The MRI technique Deoni has developed looks at the microstructure of the brain’s white matter, the tissue that contains long nerve fibers and helps different parts of the brain communicate with each other. Specifically, the technique looks for amounts of myelin, the fatty material that insulates nerve fibers and speeds electrical signals as they zip around the brain.

Deoni and his team looked at 133 babies ranging in ages from 10 months to four years. All of the babies had normal gestation times, and all came from families with similar socioeconomic statuses. The researchers split the babies into three groups: those whose mothers reported they exclusively breastfed for at least three months, those fed a combination of breastmilk and formula, and those fed formula alone. The researchers compared the older kids to the younger kids to establish growth trajectories in white matter for each group.

The study showed that the exclusively breastfed group had the fastest growth in myelinated white matter of the three groups, with the increase in white matter volume becoming substantial by age 2. The group fed both breastmilk and formula had more growth than the exclusively formula-fed group, but less than the breastmilk-only group.

“We’re finding the difference [in white matter growth] is on the order of 20 to 30 percent, comparing the breastfed and the non-breastfed kids,” said Deoni. “I think it’s astounding that you could have that much difference so early.”

Deoni and his team then backed up their imaging data with a set of basic cognitive tests on the older children. Those tests found increased language performance, visual reception, and motor control performance in the breastfed group.

The study also looked at the effects of the duration of breastfeeding. The researchers compared babies who were breastfed for more than a year with those breastfed less than a year, and found significantly enhanced brain growth in the babies who were breastfed longer — especially in areas of the brain dealing with motor function.

Deoni says the findings add to a substantial body of research that finds positive associations between breastfeeding and children’s brain health.

“I think I would argue that combined with all the other evidence, it seems like breastfeeding is absolutely beneficial,” he said.

Pioneering Study Demonstrates Benefit of Imaging Technique in Identifying Mental Illness

MRI may be an effective way to diagnose mental illnesses such as bipolar disorder, according to experts from the Icahn School of Medicine at Mount Sinai. In a landmark study using advanced techniques, the researchers were able to correctly distinguish bipolar patients from healthy individuals based on their brain scans alone. The data are published in the journal Psychological Medicine.

Currently, most mental illnesses are diagnosed based on symptoms only, creating an urgent need for new approaches to diagnosis. In bipolar disorder, there may be a significant delay in diagnosis due to the complex clinical presentation of the illness. In this study, Sophia Frangou, MD, Professor of Psychiatry and Chief of the Psychosis Research Program at the Icahn School of Medicine at Mount Sinai teamed up with Andy Simmons, MD, of the Kings College London and Janaina Mourao-Miranda, MD, of University College London, to explore whether brain imaging could help correctly identify patients with bipolar disorder.

“Bipolar disorder affects patients’ ability to regulate their emotions successfully, which puts them at great disadvantage in their lives,” said Dr. Frangou. “The situation is made worse by unacceptably long delays, sometimes of up to 10 years, in making the correct diagnosis. Bipolar disorder may be easily misdiagnosed for other disorders, such as depression or schizophrenia. This is why bipolar disorder ranks among the top ten disorders causing significant disability worldwide.”

Dr. Frangou and her team used MRI to scan the brains of people with bipolar disorder and of healthy individuals. Using advanced computational models, they were successful in correctly separating people with bipolar disorder from healthy individuals with 73 percent accuracy using their brain imaging scans alone. They replicated their finding in a separate group of patients and healthy individuals and found a 72 percent accuracy rate.

Dr. Simmons added, “The level of accuracy we achieved is comparable to that of many other tests used in medicine. Additionally, brain scanning is very acceptable to patients as most people consider it a routine diagnostic test.”

“This approach does not undermine the importance of rigorous clinical assessment and the importance of building relationships with patients but provides biological justification for the type of diagnosis made,” said Dr. Frangou. “However, diagnostic imaging for psychiatry is still under investigation and not ready for widespread use. Nonetheless, our results together with those from other labs are a harbinger of a major shift in the way we approach diagnosis in psychiatry.”