Posts tagged neuroscience
Articles and news from the latest research reports.
The brain processes complex stimuli more cumulatively than we thought
A new study reveals that the representation of complex features in the brain may begin earlier—and play out in a more cumulative manner—than previously thought.
The finding represents a new view of how the brain creates internal representations of the visual world. “We are excited to see if this novel view will dominate the wider consensus” said senior author Dr. Miyashita, who is also Professor of Physiology at the University of Tokyo’s School of Medicine, “and also about the potential impact of our new computational principle on a wide range of views on human cognitive abilities.”
The brain recalls the patterns and objects we observe by developing distinct neuronal representations that go along with them (this is the same way it recalls memories). Scientists have long hypothesized that these neuronal representations emerge in a hierarchical process limited to the same cortical region in which the representations are first processed.
Because the brain perceives and recognizes the external world through these internal images, any new information about the process by which this takes place has the power to inform our understanding of related functions, including knowledge acquisition and memory.
However, studies attempting to uncover the functional hierarchy involved in the cortical process of visual stimuli have tried to characterize this hierarchy by analyzing the activity of single nerve cells, which are not necessarily correlated with neurons nearby, thus leaving these analyses lacking.
In a new study appearing in the 12 July issue of the journal Science, lead author Toshiyuki Hirabayashi and colleagues focus not on single neurons but instead on the relationship between neuron pairs, testing the possibility that the representation of an object in a single brain region emerges in a hierarchically lower brain area.
"I became interested in this work," said Dr. Hirabayashi, "because I was impressed by the elaborate neuronal circuitry in the early visual system, which is well-studied, and I wanted to explore the circuitry underlying higher-order visual processing, which is not yet fully understood."
Hirabayashi and colleagues analyzed nerve cell pairs in cortical areas TE and 36, the latter of which is hierarchically higher, in two adult macaques. After these animals looked at six sets of paired stimuli for several months to learn to associate related objects (a process that can lead to pair-coding neurons in the brain), the researchers recorded neuron responses in areas TE and 36 of both animals as they again performed this task.
The neurons exhibited pair association, but not where the researchers would have thought. “The most surprising result,” said senior author Dr. Yasushi Miyashita “was that the neuronal circuit that generated pair-association was found only in area TE, not in area 36.” Indeed, based on previous studies, which indicated that the number of pair-coding neurons in area TE is much smaller, the researchers would have expected the opposite.
During their study, Miyashita and other team members observed that in region TE of the macaque cortex, unit 1 neurons (or source neurons) provided input to unit 2 neurons (or target neurons), which—unlike unit 1 neurons—responded to both members of a stimulus pair.
"The representations generated in area TE did not reflect a mere random fluctuation of response patterns," explained Dr. Miyashita, "but rather, they emerged as a result of circuit processing inherent to that area of the brain."
In area 36, meanwhile, members of neuron pairs behaved differently; on average, unit 1 as well as unit 2 neurons responded to both members of a stimulus pair. Neurons in area 36 received input from area TE, but only from its unit 2 neurons.
Taken together, these findings lead the authors to hypothesize the existence of a hierarchical relationship between regions TE and 36, in which paired associations first established in the former region are propagated to the latter one. Here, area 36 represents the next level of a so-called feed forward hierarchy.
The work by Hirabayashi and colleagues suggests that the detailed representations of objects commonly observed in the brain are attained not by buildup of representations in a single area, but by emergence of these representations in a hierarchically prior area and their subsequent transfer to the brain region that follows. There, they become sufficiently prevalent for the brain to register. The work also reveals that the brain activity involved in recreating visual stimuli emerges in a hierarchically lower brain area than previously thought.
Moving forward, the Japanese research team has plans to expand upon this research, thus continuing to contribute to studies worldwide that aim to give scientists the best possible tools with which to obtain a dynamic picture of the brain. As a next step, the team hopes to further elucidate interactions between the various cortical microcircuits that operate in memory encoding. Dr. Miyashita has conjectured that these microcircuits are manipulated by a global brain network. Using the results of this latest study, he and colleagues are poised to further evaluate this assumption.
"It will also be important to weave the neuronal circuit mechanisms into a unified framework," said Dr. Hirabayashi," and to examine the effects of learning on these circuit organizations."
Equipped with their new view of cortical processing, the team also hopes to trace the causal chain of memory retrieval across different areas of the cortex. “I am excited by the recent development of genetic tools that will allow us to do this,” said Dr. Miyashita. A better understanding of object representations from one area of the brain to the next will shed even greater light on elusive aspects of this hierarchical organ.
(Source: eurekalert.org)
Daydreaming simulated by computer model
Scientists have created a virtual model of the brain that daydreams like humans do.
Researchers created the computer model based on the dynamics of brain cells and the many connections those cells make with their neighbors and with cells in other brain regions. They hope the model will help them understand why certain portions of the brain work together when a person daydreams or is mentally idle. This, in turn, may one day help doctors better diagnose and treat brain injuries.
“We can give our model lesions like those we see in stroke or brain cancer, disabling groups of virtual cells to see how brain function is affected,” said senior author Maurizio Corbetta, MD, the Norman J. Stupp Professor of Neurology at Washington University School of Medicine in St. Louis. “We can also test ways to push the patterns of activity back to normal.”
The study is now available online in The Journal of Neuroscience.
The model was developed and tested by scientists at Washington University School of Medicine in St. Louis, Universitat Pompeu Fabra in Barcelona, Spain, and several other European universities including ETH Zurich, Switzerland; University of Oxford, United Kingdom; Institute of Advanced Biomedical Technologies, Chieti, Italy; and University of Lausanne, Switzerland.
Scientists first recognized in the late 1990s and early 2000s that the brain stays busy even when it’s not engaged in mental tasks. Researchers have identified several “resting state” brain networks, which are groups of different brain regions that have activity levels that rise and fall in sync when the brain is at rest. They have also linked disruptions in networks associated with brain injury and disease to cognitive problems in memory, attention, movement and speech.
The new model was developed to help scientists learn how the brain’s anatomical structure contributes to the creation and maintenance of resting state networks. The researchers began with a process for simulating small groups of neurons, including factors that decrease or increase the likelihood that a group of cells will send a signal.
“In a way, we treated small regions of the brain like cognitive units: not as individual cells but as groups of cells,” said Gustavo Deco, PhD, professor and head of the Computational Neuroscience Group in Barcelona. “The activity of these cognitive units sends out excitatory signals to the other units through anatomical connections. This makes the connected units more or less likely to synchronize their signals.”
Based on data from brain scans, researchers assembled 66 cognitive units in each hemisphere, and interconnected them in anatomical patterns similar to the connections present in the brain.
Scientists set up the model so that the individual units went through the signaling process at random low frequencies that had previously been observed in brain cells in culture and in recordings of resting brain activity.
Next, researchers let the model run, slowly changing the coupling, or the strength of the connections between units. At a specific coupling value, the interconnections between units sending impulses soon began to create coordinated patterns of activity.
“Even though we started the cognitive units with random low activity levels, the connections allowed the units to synchronize,” Deco said. “The spatial pattern of synchronization that we eventually observed approximates very well—about 70 percent—to the patterns we see in scans of resting human brains.”
Using the model to simulate 20 minutes of human brain activity took a cluster of powerful computers 26 hours. But researchers were able to simplify the mathematics to make it possible to run the model on a typical computer.
“This simpler whole brain model allows us to test a number of different hypotheses on how the structural connections generate dynamics of brain function at rest and during tasks, and how brain damage affects brain dynamics and cognitive function,” Corbetta said.
Extroverts have more sensitive brain-reward system
Extroverts may be more outgoing and cheerful in part because of their brain chemistry, reports a study by Cornell neuroscientists.
People’s brains respond differently to rewards, say the neuroscientists. Some people’s brains release more of the neurotransmitter dopamine, which ultimately gives them more reasons to be excited and engaged with the world, says Richard Depue, professor of human development in the College of Human Ecology, who co-authored the study with graduate student Yu Fu.
Their study, published in Frontiers in Human Neuroscience in June, sheds new light on how differences in the way the brain responds to reward translate into extraverted behavior, the authors say.
“Rewards like food, sex and social interactions as well as more abstract goals such as money or getting a degree trigger the release of dopamine in the brain, producing positive emotions and feelings of desire that motivate us to work toward obtaining those goals. In extroverts, this dopamine response to rewards is more robust so they experience more frequent activation of strong positive emotions,” Depue says.
“Dopamine also facilitates memory for circumstances that are associated with the reward. Our findings suggest this plays a significant role in sustaining extroverted behavior,” Depue adds. “The extroverts in our study showed greater association of context with reward than introverts, which means that over time, extroverts will acquire a more extensive network of reward-context memories that activate their brain’s reward system.”
Over a week, the researchers engaged 70 young adult males – a mix of introverts and extroverts according to a standard personality test – in a set of laboratory tasks that included viewing brief video clips of several aspects of the lab environment. On the first four days, some participants received a low dose of the stimulant methylphenidate (MP), also known as Ritalin, which triggers the release of dopamine in the brain; the others received either a placebo or MP in a different lab location. The team tested how strongly participants associated contextual cues in the lab (presented in video clips) with reward (the dopamine rush induced by MP) by assessing changes in their working memory, motor speed at a finger-tapping task and positive emotions (all known to be influenced by dopamine).
Participants who had unconsciously associated contextual cues in the lab with the reward were expected to have greater dopamine release/reward system activation on day 4 compared with day 1 when shown the same video clips. This so-called “associative conditioning” response is exactly what the team found in the extroverts. The extroverts strongly associated the lab context with reward feelings, whereas the introverts showed little to no evidence of associative conditioning.
“At a broader level, the study begins to illuminate how individual differences in brain functioning interact with environmental influences to create behavioral variation. This knowledge may someday help us to understand how such interactions create more extreme forms of emotional behavior, such as personality disorders,” says Depue.
Study Finds Factors That May Cause Fluctuations in Deep Brain Stimulation Levels Over Time
Deep brain stimulation therapy blocks or modulates electrical signals in the brain to improve symptoms in patients suffering from movement disorders such as Parkinson’s disease, essential tremor and dystonia, but a new study suggests that several factors may cause electrical current to vary over time.
Led by Michele Tagliati, MD, director of Cedars-Sinai Medical Center’s Movement Disorders Program, the study identified variables that affect impedance – resistance in circuits that affect intensity and wavelength of electrical current. Doctors who specialize in programming DBS devices fine-tune voltage, frequency and other parameters for each patient; deviations from these settings may have the potential to alter patient outcomes.
“Deep brain stimulation devices are currently designed to deliver constant, steady voltage, and we believe consistency and reliability are critical in providing therapeutic stimulation. But we found that we cannot take impedance stability for granted over the long term,” said Tagliati, the senior author of a journal article that reveals the study’s findings.
“Doctors with experience in DBS management can easily make adjustments to compensate for these fluctuations, and future devices may do so automatically,” he added. “Although our study was not designed to link changes in impedance and voltage with clinical outcomes, we believe it is important for patients to have regular, ongoing clinic visits to be sure they receive a steady level of stimulation to prevent the emergence of side effects or the re-emergence of symptoms.”
Findings of the study – one of the largest of its kind and possibly the first to follow patients for up to five years – were published online ahead of print in Brain Stimulation. Researchers collected 2,851 impedance measurements in 94 patients over a period of six months to five years, evaluating fluctuations in individual patients and in individual electrodes. They looked at a variety of factors, including how long a patient had undergone treatment, the position of the implanted electrode, the side of the brain where the electrode was implanted, and even placement and function of contact positions along electrodes.
Medications usually are the first line of treatment for movement disorders, but if drugs fail to provide adequate relief or side effects are excessive, neurologists and neurosurgeons may supplement them with deep brain stimulation. Electrical leads are implanted in the brain, and an electrical pulse generator is placed near the collarbone. The device is then programmed with a remote, hand-held controller.
(Source: newswise.com)
Cry analyzer seeks clues to babies’ health
Researchers at Brown University and Women & Infants Hospital have developed a new tool that analyzes the cries of babies, searching for clues to potential health or developmental problems. Slight variations in cries, mostly imperceptible to the human ear, can be a “window into the brain” that could allow for early intervention.
To parents, a baby’s cry is a signal of hunger, pain, or discomfort. But to scientists, subtle acoustic features of a cry, many of them imperceptible to the human ear, can hold important information about a baby’s health.
A team of researchers from Brown University and Women & Infants Hospital of Rhode Island has developed a new computer-based tool to perform finely tuned acoustic analyses of babies’ cries. The team hopes their baby cry analyzer will lead to new ways for researchers and clinicians to use cry in identifying children with neurological problems or developmental disorders.
“There are lots of conditions that might manifest in differences in cry acoustics,” said Stephen Sheinkopf, assistant professor of psychiatry and human behavior at Brown, who helped develop the new tool. “For instance, babies with birth trauma or brain injury as a result of complications in pregnancy or birth or babies who are extremely premature can have ongoing medical effects. Cry analysis can be a noninvasive way to get a measurement of these disruptions in the neurobiological and neurobehavioral systems in very young babies.”
The new analyzer is the result of a two-year collaboration between faculty in Brown’s School of Engineering and hospital-based faculty at Women & Infants Hospital. A paper describing the tool is in press in the Journal of Speech, Language and Hearing Research.
The system operates in two phases. During the first phase, the analyzer separates recorded cries into 12.5-millisecond frames. Each frame is analyzed for several parameters, including frequency characteristics, voicing, and acoustic volume. The second phase uses data from the first to give a broader view of the cry and reduces the number of parameters to those that are most useful. The frames are put back together and characterized either as an utterance — a single “wah” — or silence, the pause between utterances. Longer utterances are separated from shorter ones and the time between utterances is recorded. Pitch, including the contour of pitch over time, and other variables can then be averaged across each utterance.
In the end, the system evaluates for 80 different parameters, each of which could hold clues about a baby’s health.
“It’s a comprehensive tool for getting as much important stuff out of a baby cry that we can,” said Harvey Silverman, professor of engineering and director of Brown’s Laboratory for Engineering Man/Machine Systems.
To understand what important stuff to look for, Silverman and his graduate students Brian Reggiannini and Xiaoxue Li worked closely with Sheinkopf and Barry Lester, director of Brown’s Center for the Study of Children at Risk.
“We looked at them as the experts about the kinds of signals we might want to get,” Silverman said, “and we engineers were the experts on what we might actually be able to implement and methods to do so. So working together worked quite well.”
Lester, who has studied baby cries for years, says this vein of research goes back to the 1960s and a disorder called Cri du chat syndrome.
Cri du chat (cry of the cat) is caused by a genetic anomaly similar to Down syndrome. Babies who have it have a distinct, high-pitched cry. While the Cri du chat is unmistakable even without sensitive machinery, Lester and others wondered whether subtler differences in cry could also be indicators of a child’s health.
“The idea is that cry can be a window into the brain,” Lester said.
If neurological deficits change the way babies are able to control their vocal chords, those tiny differences might manifest themselves in differences in pitch and other acoustic features. Lester has published several papers showing that differences in cry are linked to medical problems stemming from malnutrition, prenatal drug exposure, and other risks.
“Cry is an early warning sign that can be used in the context of looking at the whole baby,” Lester said.
The tools used in those early studies, however, are primitive by today’s standards, Lester said. In early work, recorded cries were converted to spectrograms, visual readouts of pitch changes over time. Research technicians then read and coded each spectrogram by hand. Later systems automated the process somewhat, but the research was still slow and cumbersome.
This new automated analyzer enables researchers to evaluate cries much more quickly and in much greater detail. The Brown team plans to make it available to researchers around the world in the hopes of developing new avenues of cry research.
Sheinkopf, who specializes in developmental disorders, plans to use the tool to look for cry features that might correlate with autism.
“We’ve known for a long time that older individuals with autism produce sounds or vocalizations that are unusual or atypical,” Sheinkopf said. “So vocalizations in babies have been discussed as being useful in developing early identification tools for autism. That’s been a major challenge. How do you find signs of autism in infancy?”
The answer could be encoded in a cry.
“Early detection of developmental disorders is critical,” Lester added. “It can lead to insights into the causes of these disorders and interventions to prevent or reduce the severity of impairment.”
Autism Speaks Collaborative Releases First Full Genome Sequencing for Autism Spectrum Disorders
A collaborative formed by Autism Speaks, the world’s leading autism science and advocacy organization, has found full genome sequencing examining the entire DNA code of individuals with autism spectrum disorder (ASD) and their family members to provide the definitive look at the wide ranging genetic variations associated with ASD. The study published online today in American Journal of Human Genetics, reports on full genome sequencing on 32 unrelated Canadian individuals with autism and their families, participants in the Autism Speaks Autism Genetic Resource Exchange (AGRE). The results include both inherited as well as spontaneous or de novo, genetic alterations found in one half of the affected families sequenced.
This dramatic finding of genetic risk variants associated with clinical manifestation of ASD or accompanying symptoms in 50 percent of the participants tested is promising, as current diagnostic technology has only been able to determine a genetic basis in about 20 percent of individuals with ASD tested. The large proportion of families identified with genetic alterations of concern is in part due to the comprehensive and uniform ability to examine regions of the genome possible with whole genome sequencing missed in other lower resolution genome scanning approaches.
"From diagnosis to treatment to prevention, whole genome sequencing efforts like these hold the potential to fundamentally transform the future of medical care for people with autism," stated Autism Speaks Chief Science Officer and study co-author Robert Ring, Ph.D.
The study identified genetic variations associated with risk for ASD including de novo, X-linked and other inherited DNA lesions in four genes not previously recognized for ASD; nine genes previously determined to be associated with ASD risk; and eight candidate ASD risk genes. Some families had a combination of genes involved. In addition, risk alterations were found in genes associated with fragile X or related syndromes (CAPRIN1 and AFF2), social-cognitive deficits (VIP), epilepsy (SCN2A and KCNQ2) as well as NRXN1 and CHD7, which causes ASD-associated CHARGE syndrome.
“Whole genome sequencing offers the ultimate tool to advance the understanding of the genetic architecture of autism,” added lead author Dr. Stephen Scherer, senior scientist and director of the Centre for Applied Genomics at The Hospital for Sick Children (SickKids) and director of the McLaughlin Centre at the University of Toronto. “In the future, results from whole genome sequencing could highlight potential molecular targets for pharmacological intervention, and pave the way for individualized therapy in autism. It will also allow for earlier diagnosis of some forms of autism, particularly among siblings of children with autism where recurrence is approximately 18 per cent.”
This $1 million collaboration of Autism Speaks, SickKids, BGI and Duke University piloted Autism Speaks’ initiative to generate the world’s largest library of sequenced genomes of individuals with ASD announced in late 2011. “As we continue to test more individuals and their family members from the AGRE cohort, we expect to discover and study additional genetic variants associated with autism. This collaboration will accelerate basic and translational research in autism and related developmental disabilities,” concluded Autism Speaks Vice President for Scientific Affairs Andy Shih, Ph.D. who oversees the collaboration, “and this collection of sequenced genomes will facilitate new collaborations engaging researchers around the world, and enable public and private entities to pursue pivotal research.”
In this pilot effort, a total of 99 individuals were tested, including the 32 individuals with ASD (25 males and seven females) and their two parents, as well as three members of one control family not on the autism spectrum. Using families in the Autism Speaks AGRE collection, this Autism Speaks initiative will ultimately perform whole genome sequencing on more than 2,000 participating families who have two or more children on the autism spectrum. The data from the 10,000 AGRE participants will enable new research in the genomics of ASD, and significantly enhance the science and technology networks of Autism Speaks and its collaborators.
(Source: autismspeaks.org)
The Brain on Stress: Vulnerability and Plasticity of the Prefrontal Cortex over the Life Course
The prefrontal cortex (PFC) is involved in working memory and self-regulatory and goal-directed behaviors and displays remarkable structural and functional plasticity over the life course. Neural circuitry, molecular profiles, and neurochemistry can be changed by experiences, which influence behavior as well as neuroendocrine and autonomic function. Such effects have a particular impact during infancy and in adolescence. Behavioral stress affects both the structure and function of PFC, though such effects are not necessarily permanent, as young animals show remarkable neuronal resilience if the stress is discontinued. During aging, neurons within the PFC become less resilient to stress. There are also sex differences in the PFC response to stressors. While such stress and sex hormone-related alterations occur in regions mediating the highest levels of cognitive function and self-regulatory control, the fact that they are not necessarily permanent has implications for future behavior-based therapies that harness neural plasticity for recovery.
Females Respond Better to Stress Because of Estrogen in the Brain, Animal Study Finds
The idea that females are more resilient than males in responding to stress is a popular view, and now University at Buffalo researchers have found a scientific explanation. The paper describing their embargoed study will be published July 9 online, in the high-impact journal, Molecular Psychiatry.
“We have examined the molecular mechanism underlying gender-specific effects of stress,” says senior author Zhen Yan, PhD, a professor in the Department of Physiology and Biophysics in the UB School of Medicine and Biomedical Sciences. “Previous studies have found that females are more resilient to chronic stress and now our research has found the reason why.”
The research shows that in rats exposed to repeated episodes of stress, females respond better than males because of the protective effect of estrogen.
In the UB study, young female rats exposed to one week of periodic physical restraint stress showed no impairment in their ability to remember and recognize objects they had previously been shown. In contrast, young males exposed to the same stress were impaired in their short-term memory.
An impairment in the ability to correctly remember a familiar object signifies some disturbance in the signaling ability of the glutamate receptor in the prefrontal cortex, the brain region that controls working memory, attention, decision-making, emotion and other high-level “executive” processes.
Last year, Yan and UB colleagues published in Neuron a paper showing that repeated stress results in loss of the glutamate receptor in the prefrontal cortex of young males.
The current paper shows that the glutamate receptor in the prefrontal cortex of stressed females is intact. The findings provide more support for a growing body of research demonstrating that the glutamate receptor is the molecular target of stress, which mediates the stress response.
The stressors used in the experiments mimic challenging and stressful, but not dangerous, experiences that humans face, such as those causing frustration and feelings of being under pressure, Yan says.
By manipulating the amount of estrogen produced in the brain, the UB researchers were able to make the males respond to stress more like females and the females respond more like males.
“When estrogen signaling in the brains of females was blocked, stress exhibited detrimental effects on them,” explains Yan. “When estrogen signaling was activated in males, the detrimental effects of stress were blocked.
“We still found the protective effect of estrogen in female rats whose ovaries were removed,” says Yan. “It suggests that it might be estrogen produced in the brain that protects against the detrimental effects of stress.”
In the current study, Yan and her colleagues found that the enzyme aromatase, which produces estradiol, an estrogen hormone, in the brain, is responsible for female stress resilience. They found that aromatase levels are significantly higher in the prefrontal cortex of female rats.
“If we could find compounds similar to estrogen that could be administered without causing hormonal side effects, they could prove to be a very effective treatment for stress-related problems in males,” she says.
She notes that while stress itself is not a psychiatric disorder, it can be a trigger for the development of psychiatric disorders in vulnerable individuals.
(Source: newswise.com)
Children who were later diagnosed with autism spectrum disorder had excessive cerebrospinal fluid and enlarged brains in infancy, a study by a multidisciplinary team of researchers with the UC Davis MIND Institute has found, raising the possibility that those brain anomalies may serve as potential biomarkers for the early identification of the neurodevelopmental disorder.
The study is the first to follow the brain-growth trajectories from infancy in children who later develop autism and the first to associate excessive cerebrospinal fluid during infancy with autism. “Early Brain Development and Elevated Extra-Axial Fluid in Infants who Develop Autism Spectrum Disorder,” is published online today in the neurology journal Brain, published by Oxford University Press.
"This is the first report of an infant brain anomaly associated with autism that is detectable by using conventional structural MRI,” said MIND Institute Director of Research David Amaral, who co-led the study.
"This study raises the potential of developing a very early method of detecting autism spectrum disorder. Early detection is critical, because early intervention can decrease the cognitive and behavioral impairments associated with autism and may result in more positive long-term outcomes for the child,” Amaral said.
The study was conducted in 55 infants between 6 and 36 months of age, 33 of whom had an older sibling with autism. Twenty-two infants were children with no family history of the condition.
The researchers reported that the brain anomaly was detected significantly more often in the high-risk infants who were later diagnosed with autism between 24 and 36 months. Prior research by Sally Ozonoff, the vice chair for research and professor in the Department of Psychiatry and Behavioral Sciences, who co-led the study, has shown that the risk of autism is nearly 20 times greater in siblings of children with autism than in the general population. The U. S. Centers for Disease Control and Prevention puts the overall incidence of autism at 1 in 88.
The excessive cerebrospinal fluid and enlarged brain volume were detected by periodically measuring the infants’ brain growth and development using magnetic resonance imaging (MRI), and by regularly assessing their cognitive, social, communication and motor development. Both the high- and low-risk infants underwent their first MRI scans at 6 to 9 months. The second MRI scans occurred when they were 12 to 15 months old. The third was conducted between 18 and 24 months. The MRIs were conducted while the infants were sleeping naturally, without the need for sedation or anesthesia.
At 6 months, the researchers began intensive behavioral assessments of the infants’ development. Their parents also periodically completed questionnaires about their babies’ behaviors. These tests were conducted until the infants were 24 to 36 months old, when each child was evaluated as having autism spectrum disorder, other developmental delays, or typical development.
In addition to the 10 children diagnosed with autism, 24 percent of the high-risk and 13.5 percent of the low-risk infants were classified as having other developmental delays. Some 45.5 percent of high-risk and over 86 percent of low-risk babies were found to be developing normally.
The researchers found that by 6 to 9 months of age, the children who developed autism had elevated cerebrospinal fluid levels in the “extra-axial” space above and surrounding the brain, and that those fluid levels remained abnormally elevated between 18 to 24 months of age. The more fluid during early infancy, the more severe were the child’s autism symptoms when diagnosed, the study found.
In the infants who would go on to be diagnosed with autism, the ”extra-axial” fluid volume was, on average, 33 percent greater at 12 to 15 months and 22 percent greater at 18 to 24 months, when compared with typically developing infants. At 6 to 9 months, the extra-axial fluid volume was 20 percent greater, when compared with typically developing infants.
The study also provided the first MRI evidence of brain enlargement in autism prior to 24 months. The infants in the study diagnosed with autism had, on average, 7 percent larger brain volumes at 12 months, compared with the typically developing infants.
The excessive extra-axial fluid and enlarged brain volume were detected by brain imaging before behavioral signs of autism were evident. “The cause of the increased extra-axial fluid and enlarged brain size is currently unknown”, Amaral said.
Early diagnosis may be of particular benefit to infants whose older siblings have been diagnosed with autism, but the researchers caution that this finding must be replicated before it could aid in the early diagnosis of ASD. The MIND Institute is currently collaborating with other research institutions to replicate these findings and to evaluate how well the potential biomarker can accurately predict a later diagnosis of ASD.
“It is critical to understand how often this brain finding is present in children who do not develop autism, as well,” said Ozonoff. “For a biomarker to be useful in predicting autism outcomes, we want to be sure it does not produce an unacceptable level of false positives.”
“If this finding of elevated extra-axial fluid is replicated in a larger sample of infants who develop autism, and it accurately distinguishes between infants who do not develop autism, it has the potential of becoming a noninvasive biomarker that would aid in early detection, and ultimately improve the long-term outcomes of these children through early intervention,” said Mark Shen, UC Davis graduate student and the study’s lead author.
The brain’s response to sweets may indicate risk for development of alcoholism
Several human and animal studies have shown a relationship between a preference for highly sweet tastes and alcohol use disorders. Furthermore, the brain mechanisms of sweet-taste responses may share common neural pathways with responses to alcohol and other drugs. A new study using functional magnetic resonance imaging (fMRI) has found that recent drinking is related to the orbitofrontal-region brain response to an intensely sweet stimulus, a brain response that may serve as an important phenotype, or observable characteristic, of alcoholism risk.
Results will be published in the December 2013 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.
"It has long-been known that animals bred to prefer alcohol also drink considerably greater quantities of sweetened water than do animals without this selective breeding for alcohol preference," explained David A. Kareken, deputy director of the Indiana Alcohol Research Center, a professor in the department of neurology at Indiana University School of Medicine, and corresponding author for the study. "More recently, it has become clear that animals bred to prefer the artificial sweetener, saccharin, also drink more alcohol. Although the data in humans are somewhat more variable, some studies do show that alcoholics, or even non-alcoholics with a family history of alcoholism, have a preference for unusually sweet tastes. Thus, while the precise reasons remain unclear, there does seem to be significant evidence suggesting some link between the rewarding properties of both sweet tastes and alcohol."
Kareken added that this is the first study to examine the extent to which regions of the brain’s reward system, as they respond to an intensely sweet taste, are related to human drinking patterns.
Kareken and his colleagues recruited 16 (12 males, 4 females) right-handed, non-treatment seeking, healthy volunteers with a mean age of 26 years from the community. All participants underwent a taste test using a range of sucrose concentrations, and their blood oxygen dependent (BOLD) activation was measured during an fMRI scan while receiving small squirts of either water or an intensely sweet mixture of sugar in water. All were asked about their drinking patterns.
"Our study was designed to determine which brain areas responded to sweet taste – as compared to plain water – and the extent to which these brain responses were related to subjects’ binge-drinking patterns, the number of alcoholic drinks subjects consumed per day when drinking," explained Kareken.
"In addition to ‘activating’ the brain’s gustatory or taste circuits, the sugared water also activated key elements of what neuroscientists consider to be part of the brain’s reward system, including the ventral striatum, amygdala, and parts of the orbitofrontal cortex – the inferior frontal lobe surface just above the eyes – that respond to ingested rewards," Kareken said. "We refer to these as ‘primary’ rewards, being distinct from secondary rewards, like money, which can be used to obtain primary rewards."
What the researchers found was that the response to this intensely sweet taste in the left orbitofrontal area correlated significantly with subjects’ drinking patterns.
"Specifically, the trend was such that those who drank more alcohol on drinking days had stronger left orbitofrontal responses to the intensely sweet water," said Kareken. "Subjects’ subjectively rated liking of the sweetened water also contributed to this relationship, so that both the brain response itself, as well as liking of the sugared water, collectively correlated with drinking behavior."
While previous human and animal research has noted this association between preferences for both sweet tastes and alcohol intoxication, Kareken believes that this is the first study to examine the human brain mechanism behind this association.
"While much more research needs to be done to truly understand the commonalities between sweet-liking and alcoholism, and while alcoholism itself is likely the product of several mechanisms, our findings may implicate a particular brain region that is more generally involved in coding for the value of ‘primary’ rewards such as pleasures," he said. "In a more practical sense, the findings are compelling evidence that the brain response to an intensely sweet taste may be used in future research to test for differences in the reward circuits of those at risk for alcoholism. This may be particularly useful since alcohol itself is not an easy drug to work with in this kind of human imaging, and since alcohol exposure is not ethically appropriate for use in all at-risk subjects, or in subjects trying to abstain from drinking."
(Source: eurekalert.org)