Category: Autism

An investigational compound that targets the core symptoms of fragile X syndrome is effective for addressing the social withdrawal and challenging behaviors characteristic of the condition, making it the first such discovery for fragile X syndrome and, potentially, the first for autism spectrum disorder, a study by researchers at the UC Davis MIND Institute and Rush University Medical Center, Chicago, has found.

The finding is the result of a clinical trial in adult and pediatric subjects with fragile X syndrome. It suggests, however, that the compound may have treatment implications for at least a portion of the growing population of individuals with autism spectrum disorder, as well as for those with other conditions defined by social deficits. The study is published online today in the journal Science Translational Medicine. A second study by the manufacturer of the compound is included in the same issue.

The "first-in-patient" drug trial was led by internationally recognized fragile X researchers Elizabeth Berry-Kravis of Rush University Medical Center and Randi Hagerman of the UC Davis MIND Institute. It examined the effects of the compound STX 209, also known by the name arbaclofen.

The study was conducted collaboratively with Seaside Therapeutics, a Cambridge, Mass., pharmaceutical company that is focused on translating bench research on fragile X and autism into therapeutic interventions. Seaside Therapeutics produces the compound.

"This study shows that STX 209 is an important part of the treatment for fragile X syndrome, because it improved symptoms in those with significant social deficits or autism as well as fragile X syndrome," said Hagerman, medical director of the MIND Institute. "Additional studies also are suggesting that STX 209 can be helpful for autism without fragile X syndrome. Until now, there have been no targeted treatments available for autism. This appears to be the first."

Fragile X syndrome is the most common known cause of inherited intellectual impairment, formerly referred to as mental retardation, and the leading known single-gene cause of autism. Social impairment is one of the core deficits in both fragile X and autism. The U.S. Centers for Disease Control and Prevention (CDC) estimates that about 1 in 4,000 males and 1 in 6,000 to 8,000 females have the disorder. An estimated 1 in 88 children born today will be diagnosed with autism, according to the CDC.

"There are no Food and Drug Administration-approved treatments for fragile X syndrome, and the available options help secondary symptoms, but do not effectively address the core impairments in fragile X. This is the first large-scale study that is based on the molecular understanding of fragile X and suggests that the core symptoms may be amenable to pharmacologic treatment," said lead study author Elizabeth Berry-Kravis, professor of pediatrics, neurological sciences and biochemistry at Rush University Medical Center.

"This study will help to signal the beginning of a new era of targeted treatments for genetic disorders that have historically been regarded as beyond the reach of pharmacotherapy," Berry-Kravis said. "It will be a model for treatment of autism, intellectual disability and developmental brain disorders based on understanding of dysfunction in brain pathways, as opposed to empiric treatment of symptoms. We hope mechanistically based treatments like STX209 ultimately will be shown to improve cognitive functioning in longer-term trials."

Studies in mice genetically engineered to exhibit features of fragile X, including social impairment, have suggested that the behavioral abnormalities in fragile X result from deficiencies in the neurotransmitter gamma-amino butyric acid (GABA). Decreased GABA has been observed in a mouse model of fragile X in many areas of the brain including the hippocampus, and has been hypothesized to be a basis of the social anxiety and avoidance characteristic of fragile X sufferers, the study says.

Arbaclofen is an agonist for gamma-amino butyric acid type B, or GABA-B, receptors. An agonist is a chemical that effectively combines with a receptor on a synapse to effect a physiologic reaction typical of a naturally occurring substance. Anxiety-driven repetitive behavior and social avoidance have been reduced in fragile X-engineered mice treated with arbaclofen. The current, first-of-its-kind study investigated whether arbaclofen would produce similar results in human subjects.

The double-blind, placebo-controlled clinical trial initially recruited 63 male and female subjects at 12 sites across the United States for the research, conducted between December 2008 and March 2010. The participants ranged in age from 6 to 39 years. Of the initial participants, 56 completed the clinical trial. There were no withdrawals related to drug tolerability. The majority of the subjects were treated with what was assessed as the optimum tolerated dosage of the study drug, 10 milligrams twice a day in younger patients and three times a day in adults. Compliance was monitored by patient guardians, who filled out a dosing form on a daily basis.

The study subjects returned for evaluations at two- and four-week intervals after beginning the six-week-long treatment. The drug then was tapered down over a one- to two-week period.

The effects of the medication were scored on variables of the Aberrant Behavior Checklist (ABC), a behavior-rating scale for the assessment of drug-treatment effects. The checklist includes variables for irritability, lethargy/withdrawal, stereotypic (repetitive) behavior and hyperactivity, among other factors.

The study found improvement for the full study population on the social-avoidance subscale, an analysis validated by secondary ratings from parent observation of improvement in subjects' three most problematic behaviors. It found that the medication was the same as placebo, however, on the subscale for irritability.

The study is one of several at the MIND Institute aiming to help improve behavior and cognition for individuals with fragile X syndrome and autism spectrum disorder.

"We are looking forward to further studies utilizing STX 209 in both autism and fragile X syndrome because the fragile X mouse studies demonstrate long-term strengthening of synaptic connections with continued use of this medication," Hagerman said.

Other study authors include David R. Hessl, Yi Mu and Danh V. Nguyen of UC Davis; Barbara Rathmell, Peter Zarevics, Maryann Cherubini, Karen Walton-Bowen, Paul P. Wang and Randall L. Carpenter of Seaside Therapeutics; Joseph Gonzalez-Heydrich of Boston Children's Hospital; and Mark F. Bear of the Massachusetts Institute of Technology.

Parents should not worry that proposed changes to the medical criteria redefining a diagnosis of autism will leave their children excluded and deemed ineligible for psychiatric and medical care, says a team of researchers led by psychologists at Weill Cornell Medical College.

Their new study, published in the October 1 issue of the American Journal of Psychiatry, is the largest to date that has tried to unpack the differences between the diagnostic criteria for autism spectrum disorders in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and the proposed revision in the fifth edition (DSM-5), which is expected to be published in May 2013. These manuals provide diagnostic criteria for people seeking mental-health-related medical services.

"I know that parents worry, but I don't believe there is any substantial reason to fear that children who need to be diagnosed with autism spectrum disorders, and provided with vital services, will not be included in the new criteria in this updated manual," says the study's senior investigator, Dr. Catherine Lord, director of the Center for Autism and the Developing Brain at NewYork-Presbyterian Hospital's Westchester campus, along with its affiliated medical schools Weill Cornell Medical College and Columbia University College of Physicians and Surgeons.

At issue is whether DSM-5 will "capture" the same individuals diagnosed with different forms of autism by the DSM-IV. The DSM-5 proposal redefines autism as a single category — autism spectrum disorder (ASD) — whereas DSM-IV had multiple categories and included Autistic Disorder, Asperger's Disorder, and Pervasive Developmental Disorder, Not Otherwise Specified (PDD-NOS).

Critics have particularly worried that among the excluded will be children now diagnosed with PPD-NOS and Asperger's disorder. That isn't the case, says Dr. Lord, who is also a DeWitt Wallace Senior Scholar at Weill Cornell and an attending psychologist at NewYork-Presbyterian Hospital. The study, the largest to date and arguably, the most rigorous, finds that when relying on parent report, 91 percent of the 4,453 children in the sample currently diagnosed with a DSM-IV autism spectrum disorder would be diagnosed with ASD using DSM-V.

Many of the remaining nine percent would likely be reincluded once a clinician can offer input, says Dr. Lord, who is also a member of the American Psychiatric Association's DSM-5 Neurodevelopmental Disorders Work Group.

The study researchers also concluded that DSM-5 has higher specificity than DSM-IV–in their study, DSM-5 criteria resulted in fewer misclassifications.

Improving the Diagnostic Criteria

The study used three large databases to evaluate DSM-5 criteria in groups of children with DSM-IV clinical diagnoses. The analysis, which included a team of independent reviewers led by the study's lead author, Dr. Marisela Huerta of NewYork-Presbyterian/Weill Cornell Medical Center, relied on a standardized 96-item parent report and a clinician-based measure of autism spectrum disorder impairments.

"These two instruments were particularly well-suited for the current study because they include items based on history and current behavior, and they take into account developmental level in their design," says Dr. Huerta, an instructor of psychology at Weill Cornell and a professional associate at NewYork-Presbyterian Hospital. "This is consistent with DSM-5 criteria, which operationalize symptoms differently for individuals of different ages in order to account for the effect of development on ASD symptoms."

The changes proposed by DSM-5 are designed to better identify autism spectrum disorders and distinguish them from other conditions. According to Dr. Huerta, "The criteria for DSM-5 are actually more inclusive." For example, while DSM-IV criteria require evidence of difficulties related to autism prior to age 3, "DSM-5 says that a child has to show examples of unusual behavior in early childhood, with the idea that there is nothing sacrosanct about your third birthday."

Other changes proposed by DSM-5 include defining autism spectrum disorders by two sets of core features — impaired social communication and social interactions, and restricted and repetitive behavior and interests. DSM-5 reorganizes the symptoms in these domains and includes those not previously included in DSM-IV, such as sensory interests and aversions.

The overall issue with DSM-IV was "not that a lot of people are diagnosed with autism who shouldn't be, but that there is a lot of confusion because the criteria were not very accurate," says Dr. Lord.

"DSM-5 deliberately added and organized things to try to bring in and better address the needs of people with autism spectrum disorders of all developmental levels and ages — including girls, who were not represented as well as they should be in DSM-IV," Dr. Lord says. "The goal of DSM-5 is to better describe who has ASD in a way that matches up with what we know from research, which predicts who has the disorder and also reflects what clinicians are actually looking at."

Because of the newness of the proposed criteria, only a few studies have attempted to compare the criteria between the two DSM versions. "Our study is much broader, and it is important to note that we get very similar results when looking at three large data sets that were collected for different purposes, with diverse populations, and for various reasons," says Dr. Lord.

The study's other contributing authors are Dr. Somer L. Bishop of NewYork-Presbyterian/Weill Cornell Medical Center, Dr. Amie Duncan from Cincinnati Children's Hospital Medical Center, and graduate student Vanessa Hus from the University of Michigan.

The research was supported by grants from the National Institute of Mental Health and the National Institute of Child Health and Human Development.

Dr. Catherine Lord was involved in the development of some of the instruments used in this research and receives royalty income from the sale of those instruments.

A new study published October 8 in the journal Pediatrics found that nearly half of children with autism spectrum disorders (ASD) are reported to wander or "bolt," and more than half of these children go missing. Led by researchers from the Interactive Autism Network (IAN), the nation's largest online autism research initiative and a project of the Kennedy Krieger Institute, this study provides the most comprehensive estimate of elopement occurrence in a United States community-based sample of more than 1,200 children with ASD.

"Since the launch of IAN, we have heard from families of children with autism that their children often place themselves in danger by wandering or eloping," says Dr. Paul Law, senior author and director of the IAN Project at the Kennedy Krieger Institute. "These are the first published findings in the U.S. that provide an estimate of the number of children with ASD who not only wander or elope, but go missing long enough to cause real concern."

Participants in the study included families of 1,218 children with ASD and 1,076 of their siblings without ASD recruited through an online questionnaire. The primary outcome measured by researchers was elopement status beginning at age 4, when elopement and wandering are increasingly atypical behaviors. "Missing" status was a secondary outcome; a child who eloped and had gone missing long enough to cause concern was coded as missing, whereas those who had not were coded as non-missing. The study's findings on elopement prevalence, characteristics correlated with elopement and qualitative measures of family stress are presented below.

Elopement Prevalence

• 49 percent of children with ASD attempted to elope at least once after age 4.
• Of those who attempted to elope, 53 percent of children with ASD went missing long enough to cause concern.
• From age 4 to 7, 46 percent of children with ASD eloped, which is four times the rate of unaffected siblings.
• From age 8 to 11, 27 percent of affected children elopedcompared with 1 percent of unaffected siblings.

Elopement Behavior

• When eloping, 74 percent of affected children eloped from their own home or someone else's home. Children also eloped from stores (40 percent) and classroom or schools (29 percent).
• Close calls with traffic injury were reported for 65 percent of the missing children.
• Close calls with drowning were reported for 24 percent of the missing children.
• Elopement attempts peaked at age 5.4 years. Of parents reporting on the "worst year ever," 29 percent saidthat their child attempted to elope multiple times a day; an additional 35 percent reported that attempts occurred at least once per week.
• While eloping, children with Asperger disorder were more frequently described by their parents as anxious; children with ASD were more frequently described as happy, playful or exhilarated. In either case, elopement was goal oriented, with the intent to go somewhere or do something.

Characteristics of Eloping

• Children who have eloped are older, more likely to have an ASD, present more severe autism symptoms and have lower intellectual and communication scores than non-elopers.
• Children who were reported as missing were older, more likely to have experienced skill loss and less likely to respond to their name. They were also more likely to have lower intellectual and communication scores than non-missing children.
• On average, children were missing for 41.5 minutes.

Impact of Elopement on Family

• 56 percent of parents reported elopement as one of the most stressful behaviors they had to cope with as caregivers of a child with ASD.
• 50 percent of parents reported receiving no guidance from anyone on preventing or addressing their child's elopement behavior.
• After children went missing, parents most frequently contacted neighbors (57 percent). Parents also called police (35 percent), school (30 percent) and store personnel (26 percent).

"We hope that the results of this study will inform families, physicians, educators and first responders of the real consequences of elopement," says Dr. Law. "Parents often fear being viewed as neglectful when their children leave from safe places. This study demonstrates that we urgently need interventions to address elopement and provide support to affected families."

Future research is needed to determine whether there are different types of elopement, requiring different prevention strategies. With a greater understanding of elopement, researchers will have the ability to develop more targeted interventions to assist parents in coping with this extremely stressful behavior.

This research was funded by the Autism Research Institute, Autism Science Foundation, Autism Speaks, Global Autism Collaboration, and National Autism Association.

A promising study out October 3 in the Journal of Neuroscience showed that in a mouse model of Rett syndrome, researchers were able to reverse abnormalities in brain activity and improve neurological function by treating the animals with an FDA-approved anesthesia drug, ketamine. Rett syndrome is among the most severe autism-related disorders, affecting about one in 10,000 female births per year, with no effective treatments available.

"These studies provide new evidence that drug treatment can reverse abnormalities in brain function in Rett syndrome mice," says David Katz, PhD, professor of neurosciences, Case Western Reserve University School of Medicine and senior author of the study. "They also provide new leads as to what kinds of drugs might be effective in individuals with Rett syndrome."

Neuroscientists at Case Western Reserve University School of Medicine were able to successfully map differences in the brain activity of normal mice and those with a genetic mutation that mirrors the cause of Rett syndrome in humans. They found that — compared to normal mice — Rett syndrome mice showed regions of abnormally low activity in the front of the brain (forebrain) and regions of abnormally high activity in the back of the brain (brainstem). Importantly, they found that the regions of low activity overlap with regions of the brain that are also under-active in humans with classic autism. This indicates there may be common mechanisms underlying abnormal behaviors in the two diseases.

The identification of these brain regions provided clues into specific areas to target for treatment. Based on previously published findings that ketamine activated neurons in the forebrain, the researchers gave the drug to the Rett syndrome mice and found it increased levels of brain activity in those regions and improved neurological function. Importantly, the drug was effective at a low dose that did not produce anesthesia.

Katz strongly cautioned that, because ketamine can have potent anesthetic effects and is a controlled substance, further work is needed to establish the safety of ketamine in patients with Rett syndrome. Moreover, ketamine has never been used to treat a chronic condition, and additional studies are required to determine whether or not this is feasible and safe. However, safer drugs acting in the same pathways as ketamine may be available.

Unlike most disorders on the autism spectrum, researchers know the cause of Rett syndrome — a genetic change on the X chromosome, which helps explain why it affects girls almost exclusively. Families don't usually know if a newborn has Rett syndrome because affected children can appear normal for the first six to 18 months after birth. Then, parents start to notice the infant losing the ability to speak, move, eat or even breathe normally. Many girls with Rett syndrome can live into adulthood and are so disabled that they require round-the-clock care.

One in 88 Americans is affected by an autism-related disorder, according to the Centers for Disease Control. Those affected by Rett syndrome can lose — to varying degrees — the ability for normal human interaction. They can be socially withdrawn, struggle to communicate and tend to engage in repetitive behaviors — all hallmarks of disorders that fall within the autism spectrum.

Katz's team in the School of Medicine included post-doctoral fellows Miriam Kron, PhD and Michael Ogier, PhD, research assistants C. James Howell and Ian Adams and undergraduate students Michael Ransbottom and Diana Christian. Kron and Howell are the lead authors on the Journal of Neuroscience paper.

The findings were supported by grants from the National Institute of Neurological Diseases and Stroke at the National Institutes of Health (NS-057398), the International Rett Syndrome Foundation and the first ever grant awarded in Northeast Ohio by Autism Speaks, the world's leading autism science and advocacy organization.

New results by GIGA-Neurosciences researchers (University of Liège, Belgium) increase our understanding of the mechanisms that drive neuronal migration in the cerebral cortex. Disruption of neuronal migration is associated with various neurological disorders characterized by mental retardation, epilepsy, learning disabilities, or autism.

In a study published in Developmental Cell, the group of Laurent Nguyen, Research Associate of the FRS-FNRS and WELBIO investigator at GIGA-Neurosciences (University of Liège) has discovered a novel function for p27 in the control of interneuron migration in the developing cerebral cortex.

The cerebral cortex is one of the most intricate region of the brain whose formation requires migration and integration of two classes of neurons, the projection neurons and the interneurons. These neurons are born in different places and use distinct migration modes to reach the cortex. While several signalling pathways involving various molecules have already been associated with projection neuron migration, the molecular mechanisms that control interneurons migration remain so far elusive.

In this study, the Nguyen's group unveiled a novel activity of p27, a protein initialy described for its activity as cell cycle regulator, in dynamic remodelling of the cell skeleton, named cytoskeleton, that underlies tangential migration of interneurons in the cerebral cortex. The first author of the paper, Juliette Godin who is an EMBO postdoctoral fellow in the Nguyen lab, declared : " At the molecular level, p27 acts on two cytoskeletal components, the actin and the microtubules. It promotes nucleokinesis and branching of the growth cone through regulation of actine. In addition, it promotes microtubule polymerisation in extending neurites. Both activities are required for proper tangential migration of interneurons in the cortex."

It is worth noting that microtubules are ubiquitous components of the cytoskeleton that contribute to cell integrity as well as cell migration and cell division. These cellular processes are impaired in various neurological disorders as well as in most cancers. " Our results are of particular significance because they demonstrate for the first time that p27 is a microtubule-associated protein that promote their polymerisation," said Laurent Nguyen.

Overall, these results increase our understanding of the mechanisms that drive neuronal migration in the cerebral cortex. Disruption of neuronal migration is associated with various neurological disorders characterized by mental retardation, epilepsy, learning disabilities, or autism.

The causes of autism and autism spectrum disorder (ASD) are complex, and contain elements of both nature (genes) and the environment. New research published in BioMed Central's open access journal Molecular Autism shows that common genetic polymorphisms (genetic variation) can add up to an increased risk of ASD.

The contribution of inheritance and genetic mutation versus environmental factors to the risk of ASD is hotly debated. Most twin studies show the contribution heavily tilted toward inheritance, but the exact amount of involvement of genes in ASD risk is less apparent. This is because, while the impact of rare genetic variations on ASD risk is becoming clear, the role of more common variations, so called single nucleotide polymorphisms (SNP), remains unresolved.

In a vast project involving researchers across the USA, genetic data from families in the Simons Simplex Collection (where one child, but neither parent or any brothers or sisters, have ASD) and the Autism Genome Project (where one or more children were affected), was compared to families from the HealthABC program a cross section of the population).

By analyzing one million of the common variations in each participant's genome, it became clear that, in families where only one child is affected, 40% of the risk of ASD is inherited. In families where more than one child is affected this increased to over 60%. By looking in more detail at the unaffected parents and siblings of children with ASD it appeared that the inherited risk was additive.

Prof Bernie Devlin, from the University of Pittsburgh, explained, "Each of the common variations involved in ASD has little effect on its own, however our results show that they add up. This could explain why, while the parents might each not show any symptoms, their children receive enough of the risk versions to be affected."

Overall these results suggest that there are a large number of common variants each with a very small effect. Prof Devlin continued, "This is a large step forward in our understanding of ASD. The genetic components alone are far more complex than many imagined a decade ago, including the additive effects we have found, rare inherited mutations, and new mutations arising spontaneously before conception."

Editors-in-Chief, Drs. Buxbaum and Baron-Cohen noted that this study represents "An exceptionally important breakthrough in our understanding of autism risk." They also note that, "The interplay between common SNP and rare risk variants could be key to understanding the considerable differences in presentation seen among individuals with an autism spectrum condition."

An increased risk of autism spectrum disorders (ASD) could result from an accumulation of many small, common genetic variations rather than large-effect, rare changes in the genetic code, according to a multicenter team led by researchers at the University of Pittsburgh School of Medicine. Their findings, published today in Molecular Autism, provide new insights into the genetic factors that underlie the neurodevelopmental condition.

Scientists have debated about the genetic contributions that lead to ASD in families where only one individual is affected, called simplex, versus those that have multiple affected family members, called multiplex, said senior author Bernie Devlin, Ph.D., associate professor, Department of Psychiatry, University of Pittsburgh School of Medicine.

"Our team compared simplex, multiplex and unaffected families using sophisticated quantitative genetic techniques," he said. "In families where only one child has an ASD, 40 percent of the risk is inherited while in families with more than one affected child, the risk rises to 60 percent."

For the project, the team examined thousands of DNA samples from families in the Simons Simplex Collection, in which one child but no parent or sibling had an ASD; the Autism Genome Project, in which more than one child had an ASD; and unaffected families enrolled in the HealthABC Program.

In addition to reviewing nearly 1 million gene variations, called single nucleotide polymorphisms (SNPs), to look for inheritance patterns associated with ASD, they also ran computer simulations to plot family trees using 1,000 SNPs that appear to impact the risk of ASD.

"These small gene changes can add up even though individually they do little harm," Dr. Devlin said. "This might explain why parents who do not have autism traits can have children who do."

Other research has shown that autism and related disorders also can arise from spontaneous variations in parental genes prior to conception as well as rare mutations of larger effect that are passed on, he noted. The multiple inheritance patterns could help explain the range of symptoms in the disorder.

The team included researchers from Yale University, the University of Michigan, University of California Los Angeles, Emory University, Harvard University and others. The effort was funded by grants from the Simons Foundation and National Institutes of Health grant MH057881.

Children with autism have difficulty identifying inappropriate social behavior, and even when successful, they are often unable to justify why the behavior seemed inappropriate. New brain imaging studies show that children with autism may recognize socially inappropriate behavior, but have difficulty using spoken language to explain why the behavior is considered inappropriate, according to research published Oct. 17 in the open access journal PLOS ONE by Elizabeth Carter from Carnegie Mellon University and colleagues.

The authors say the results of their functional MRI studies support previous behavioral studies that reached similar conclusions about language impairment in children with autism. In the current study, the researchers asked children with autism and children with typical development to identify in which of two pictures a boy was being bad (social judgment), or which of two pictures was outdoors (physical judgment). Both groups successfully performed the task, but the children with autism showed activity in fewer brain regions involving social and language networks while performing the task. Even though language was not required for the task, the children with typical development recruited language areas of the brain while making their decisions.

According to the authors, their results support the hypothesis that children with autism may recognize socially inappropriate behavior, but have difficulty using spoken language to explain why the behavior is considered wrong. They suggest that this decreased use of language may also make generalization of the knowledge more difficult.

"These results indicate that it is important to work with these children on translating their knowledge into language," says Carter.

New insights into the wiring and firing of the "social brain" in humans and primates reveals the brain areas important in altruistic motives and behavior, and the brain regions that respond to the pain of discrimination. The findings were presented at Neuroscience 2012, the annual meeting of the Society for Neuroscience and the world's largest source of emerging news about brain science and health.

The social brain consists of the structures and circuits that help people understand others' intentions, beliefs, and desires, and how to behave appropriately. Its smooth functioning is essential to humans' ability to cooperate. Its dysfunction is implicated in a range of disorders, from autism, to psychopathology, to schizophrenia.

Today's new findings show that:

• Primates employ three different parts of the prefrontal cortex in decisions about whether to give or keep prized treats. These findings illuminate a poorly understood brain circuit, and offer possible insights into human sharing and other social behavior (Steve Chang, PhD, abstract 129.10).
• Different brain regions are engaged in altruistic behavior that is motivated by genuine caring versus altruistic behavior motivated by a concern for reputation or self-image (Cendri Hutcherson, PhD, abstract 129.06).
• The experience of racial discrimination triggers activity in the same brain regions that respond to pain, social rejection, and other stressful experiences (Arpana Gupta, PhD, abstract 402.06).

Another recent finding discussed shows that:

• Competition against a human opponent or a computer engages the same parts of the brain, with one exception: the temporal parietal junction is used to predict only a human's upcoming actions (Ronald Carter, PhD).

"Whenever we engage with others — or even anticipate others' responses to us — the social brain is at work, shaping our actions, reactions, and interactions," said press conference moderator Anna Rose Childress, PhD, of the University of Pennsylvania, an expert in neuroimaging and addiction research. "The more we understand the brain processes that underlie basic social emotions, the better we will be able to address conditions that involve social dysfunctions."

This research was supported by national funding agencies such as the National Institutes of Health, as well as private and philanthropic organizations.

A team led by MIT neuroscientists has developed a way to monitor how brain cells coordinate with each other to control specific behaviors, such as initiating movement or detecting an odor.

The researchers' new imaging technique, based on the detection of calcium ions in neurons, could help them map the brain circuits that perform such functions. It could also provide new insights into the origins of autism, obsessive-compulsive disorder and other psychiatric diseases, says Guoping Feng, senior author of a paper appearing in the Oct. 18 issue of the journal Neuron.

"To understand psychiatric disorders we need to study animal models, and to find out what's happening in the brain when the animal is behaving abnormally," says Feng, the James W. and Patricia Poitras Professor of Neuroscience and a member of the McGovern Institute for Brain Research at MIT. "This is a very powerful tool that will really help us understand animal models of these diseases and study how the brain functions normally and in a diseased state."

Lead author of the Neuron paper is McGovern Institute postdoc Qian Chen.

Performing any kind of brain function requires many neurons in different parts of the brain to communicate with each other. They achieve this communication by sending electrical signals, triggering an influx of calcium ions into active cells. Using dyes that bind to calcium, researchers have imaged neural activity in neurons. However, the brain contains thousands of cell types, each with distinct functions, and the dye is taken up nonselectively by all cells, making it impossible to pinpoint calcium in specific cell types with this approach.

To overcome this, the MIT-led team created a calcium-imaging system that can be targeted to specific cell types, using a type of green fluorescent protein (GFP). Junichi Nakai of Saitama University in Japan first developed a GFP that is activated when it binds to calcium, and one of the Neuron paper authors, Loren Looger of the Howard Hughes Medical Institute, modified the protein so its signal is strong enough to use in living animals.

The MIT researchers then genetically engineered mice to express this protein in a type of neuron known as pyramidal cells, by pairing the gene with a regulatory DNA sequence that is only active in those cells. Using two-photon microscopy to image the cells at high speed and high resolution, the researchers can identify pyramidal cells that are active when the brain is performing a specific task or responding to a certain stimulus.

In this study, the team was able to pinpoint cells in the somatosensory cortex that are activated when a mouse's whiskers are touched, and olfactory cells that respond to certain aromas.

This system could be used to study brain activity during many types of behavior, including long-term phenomena such as learning, says Matt Wachowiak, an associate professor of physiology at the University of Utah. "These mouse lines should be really useful to many different research groups who want to measure activity in different parts of the brain," says Wachowiak, who was not involved in this research.

The researchers are now developing mice that express the calcium-sensitive proteins and also exhibit symptoms of autistic behavior and obsessive-compulsive disorder. Using these mice, the researchers plan to look for neuron firing patterns that differ from those of normal mice. This could help identify exactly what goes wrong at the cellular level, offering mechanistic insights into those diseases.

"Right now, we only know that defects in neuron-neuron communications play a key role in psychiatric disorders. We do not know the exact nature of the defects and the specific cell types involved," Feng says. "If we knew what cell types are abnormal, we could find ways to correct abnormal firing patterns."

The researchers also plan to combine their imaging technology with optogenetics, which enables them to use light to turn specific classes of neurons on or off. By activating specific cells and then observing the response in target cells, they will be able to precisely map brain circuits.

The research was funded by the Poitras Center for Affective Disorders Research, the National Institutes of Health and the McNair Foundation.

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Journal Reference:

1. Qian Chen, Joseph Cichon, Wenting Wang, Li Qiu, Seok-Jin R. Lee, Nolan R. Campbell, Nicholas DeStefino, Michael J. Goard, Zhanyan Fu, Ryohei Yasuda, Loren L. Looger, Benjamin R. Arenkiel, Wen-Biao Gan, Guoping Feng. Imaging Neural Activity Using Thy1-GCaMP Transgenic Mice. Neuron, 2012; 76 (2): 297 DOI: 10.1016/j.neuron.2012.07.011