Posts tagged neuroimaging
Posts tagged neuroimaging
Chronic trauma can inflict lasting damage to brain regions associated with fear and anxiety. Previous imaging studies of people with post-traumatic stress disorder, or PTSD, have shown that these brain regions can over-or under-react in response to stressful tasks, such as recalling a traumatic event or reacting to a photo of a threatening face. Now, researchers at NYU School of Medicine have explored for the first time what happens in the brains of combat veterans with PTSD in the absence of external triggers.
Their results, published in Neuroscience Letters, and presented today at the annual meeting of the American Psychiatry Association in San Francisco, show that the effects of trauma persist in certain brain regions even when combat veterans are not engaged in cognitive or emotional tasks, and face no immediate external threats. The findings shed light on which areas of the brain provoke traumatic symptoms and represent a critical step toward better diagnostics and treatments for PTSD.
A chronic condition that develops after trauma, PTSD can plague victims with disturbing memories, flashbacks, nightmares and emotional instability. Among the 1.7 million men and women who have served in the wars in Iraq and Afghanistan, an estimated 20% have PTSD. Research shows that suicide risk is higher in veterans with PTSD. Tragically, more soldiers committed suicide in 2012 than the number of soldiers who were killed in combat in Afghanistan that year.
“It is critical to have an objective test to confirm PTSD diagnosis as self reports can be unreliable,” says co-author Charles Marmar, MD, the Lucius N. Littauer Professor of Psychiatry and chair of NYU Langone’s Department of Psychiatry. Dr. Marmar, a nationally recognized expert on trauma and stress among veterans, heads The Steven and Alexandra Cohen Veterans Center for the Study of Post-Traumatic Stress and Traumatic Brain Injury at NYU Langone Medical Center.
The study, led by Xiaodan Yan, a research fellow at NYU School of Medicine, examined “spontaneous” or “resting” brain activity in 104 veterans of combat from the Iraq and Afghanistan wars using functional MRI, which measures blood-oxygen levels in the brain. The researchers found that spontaneous brain activity in the amygdala, a key structure in the brain’s “fear circuitry” that processes fearful and anxious emotions, was significantly higher in the 52 combat veterans with PTSD than in the 52 combat veterans without PTSD. The PTSD group also showed elevated brain activity in the anterior insula, a brain region that regulates sensitivity to pain and negative emotions.
Moreover, the PTSD group had lower activity in the precuneus, a structure tucked between the brain’s two hemispheres that helps integrate information from the past and future, especially when the mind is wandering or disengaged from active thought. Decreased activity in the precuneus correlates with more severe “re-experiencing” symptoms—that is, when victims re-experience trauma over and over again through flashbacks, nightmares and frightening thoughts.
Scientists at Washington University School of Medicine in St. Louis have helped identify many of the biomarkers for Alzheimer’s disease that could potentially predict which patients will develop the disorder later in life. Now, studying spinal fluid samples and health data from 201 research participants at the Charles F. and Joanne Knight Alzheimer’s Disease Research Center, the researchers have shown the markers are accurate predictors of Alzheimer’s years before symptoms develop.
“We wanted to see if one marker was better than the other in predicting which of our participants would get cognitive impairment and when they would get it,” said Catherine Roe, PhD, research assistant professor of neurology. “We found no differences in the accuracy of the biomarkers.”
The study, supported in part by the National Institute on Aging, appears in Neurology.
The researchers evaluated markers such as the buildup of amyloid plaques in the brain, newly visible thanks to an imaging agent developed in the last decade; levels of various proteins in the cerebrospinal fluid, such as the amyloid fragments that are the principal ingredient of brain plaques; and the ratios of one protein to another in the cerebrospinal fluid, such as different forms of the brain cell structural protein tau.
The markers were studied in volunteers whose ages ranged from 45 to 88. On average, the data available on study participants spanned four years, with the longest recorded over 7.5 years.
The researchers found that all of the markers were equally good at identifying subjects who were likely to develop cognitive problems and at predicting how soon they would become noticeably impaired.
Next, the scientists paired the biomarkers data with demographic information, testing to see if sex, age, race, education and other factors could improve their predictions.
“Sex, age and race all helped to predict who would develop cognitive impairment,” Roe said. “Older participants, men and African Americans were more likely to become cognitively impaired than those who were younger, female and Caucasian.”
Roe described the findings as providing more evidence that scientists can detect Alzheimer’s disease years before memory loss and cognitive decline become apparent.
“We can better predict future cognitive impairment when we combine biomarkers with patient characteristics,” she said. “Knowing how accurate biomarkers are is important if we are going to some day be able to treat Alzheimer’s before symptoms and slow or prevent the disease.”
Clinical trials are already underway at Washington University and elsewhere to determine if treatments prior to symptoms can prevent or delay inherited forms of Alzheimer’s disease. Reliable biomarkers for Alzheimer’s should one day make it possible to test the most successful treatments in the much more common sporadic forms of Alzheimer’s.
In a first-of-its-kind effort to illuminate the biochemical impact of trauma, researchers at NYU Langone Medical Center have discovered a connection between the quantity of cannabinoid receptors in the human brain, known as CB1 receptors, and post-traumatic stress disorder, the chronic, disabling condition that can plague trauma victims with flashbacks, nightmares and emotional instability. Their findings, which appear online today in the journal Molecular Psychiatry, will also be presented this week at the annual meeting of the Society of Biological Psychiatry in San Francisco.
CB1 receptors are part of the endocannabinoid system, a diffuse network of chemicals and signaling pathways in the body that plays a role in memory formation, appetite, pain tolerance and mood. Animal studies have shown that psychoactive chemicals such as cannabis, along with certain neurotransmitters produced naturally in the body, can impair memory and reduce anxiety when they activate CB1 receptors in the brain. Lead author Alexander Neumeister, MD, director of the molecular imaging program in the Departments of Psychiatry and Radiology at NYU School of Medicine, and colleagues are the first to demonstrate through brain imaging that people with PTSD have markedly lower concentrations of at least one of these neurotransmitters —an endocannabinoid known as anandamide—than people without PTSD. Their study, which was supported by three grants from the National Institutes of Health, illuminates an important biological fingerprint of PTSD that could help improve the accuracy of PTSD diagnoses, and points the way to medications designed specifically to treat trauma.
“There’s not a single pharmacological treatment out there that has been developed specifically for PTSD,” says Dr. Neumeister. “That’s a problem. There’s a consensus among clinicians that existing pharmaceutical treatments such as antidepressant simple do not work. In fact, we know very well that people with PTSD who use marijuana—a potent cannabinoid—often experience more relief from their symptoms than they do from antidepressants and other psychiatric medications. Clearly, there’s a very urgent need to develop novel evidence-based treatments for PTSD.”
The study divided 60 participants into three groups: participants with PTSD; participants with a history of trauma but no PTSD; and participants with no history of trauma or PTSD. Participants in all three groups received a harmless radioactive tracer that illuminates CB1 receptors when exposed to positron emissions tomography (PET scans). Results showed that participants with PTSD, especially women, had more CB1 receptors in brain regions associated with fear and anxiety than volunteers without PTSD. The PTSD group also had lower levels of the neurotransmitter anandamide, an endocannabinoid that binds to CB1. If anandamide levels are too low, Dr. Neumeister explains, the brain compensates by increasing the number of CB1 receptors. “This helps the brain utilize the remaining endocannabinoids,” he says.
Much is still unknown about the effects of anandamide in humans but in rats the chemical has been shown to impair memory. “What is PTSD? It’s an illness where people cannot forget what they have experienced,” Dr. Neumeister says. “Our findings offer a possible biological explanation for this phenomenon.”
Current diagnostics for PTSD rely on subjective measures and patient recall, making it difficult to accurately diagnose the condition or discern its symptoms from those of depression and anxiety. Biological markers of PTSD, such as tests for CB1 receptors and anandamide levels, could dramatically improve diagnosis and treatment for trauma victims.
Among the 1.7 million men and women who have served in the wars in Iraq and Afghanistan, an estimated 20% have PTSD. But PTSD is not limited to soldiers. Trauma from sexual abuse, domestic violence, car accidents, natural disaster, violent assault or even a life-threatening medical diagnosis can lead to PTSD. The condition affects nearly 8 million Americans annually.
These findings were made possible through the collaborative efforts of researchers at NYU School of Medicine, Yale School of Medicine, Harvard Medical School, the Department of Veterans Affairs National Center for PTSD and the University of California at Irvine.
(Image caption: Hypothetical cannabinoid receptor CB1 binding to anandamide)
Your brain often works on autopilot when it comes to grammar. That theory has been around for years, but University of Oregon neuroscientists have captured elusive hard evidence that people indeed detect and process grammatical errors with no awareness of doing so.
Participants in the study — native-English speaking people, ages 18-30 — had their brain activity recorded using electroencephalography, from which researchers focused on a signal known as the Event-Related Potential (ERP). This non-invasive technique allows for the capture of changes in brain electrical activity during an event. In this case, events were short sentences presented visually one word at a time.
Subjects were given 280 experimental sentences, including some that were syntactically (grammatically) correct and others containing grammatical errors, such as “We drank Lisa’s brandy by the fire in the lobby,” or “We drank Lisa’s by brandy the fire in the lobby.” A 50 millisecond audio tone was also played at some point in each sentence. A tone appeared before or after a grammatical faux pas was presented. The auditory distraction also appeared in grammatically correct sentences.
This approach, said lead author Laura Batterink, a postdoctoral researcher, provided a signature of whether awareness was at work during processing of the errors. “Participants had to respond to the tone as quickly as they could, indicating if its pitch was low, medium or high,” she said. “The grammatical violations were fully visible to participants, but because they had to complete this extra task, they were often not consciously aware of the violations. They would read the sentence and have to indicate if it was correct or incorrect. If the tone was played immediately before the grammatical violation, they were more likely to say the sentence was correct even it wasn’t.”
When tones appeared after grammatical errors, subjects detected 89 percent of the errors. In cases where subjects correctly declared errors in sentences, the researchers found a P600 effect, an ERP response in which the error is recognized and corrected on the fly to make sense of the sentence.
When the tones appear before the grammatical errors, subjects detected only 51 percent of them. The tone before the event, said co-author Helen J. Neville, who holds the UO’s Robert and Beverly Lewis Endowed Chair in psychology, created a blink in their attention. The key to conscious awareness, she said, is based on whether or not a person can declare an error, and the tones disrupted participants’ ability to declare the errors. But, even when the participants did not notice these errors, their brains responded to them, generating an early negative ERP response. These undetected errors also delayed participants’ reaction times to the tones.
“Even when you don’t pick up on a syntactic error your brain is still picking up on it,” Batterink said. “There is a brain mechanism recognizing it and reacting to it, processing it unconsciously so you understand it properly.”
The study was published in the May 8 issue of the Journal of Neuroscience.
The brain processes syntactic information implicitly, in the absence of awareness, the authors concluded. “While other aspects of language, such as semantics and phonology, can also be processed implicitly, the present data represent the first direct evidence that implicit mechanisms also play a role in the processing of syntax, the core computational component of language.”
It may be time to reconsider some teaching strategies, especially how adults are taught a second language, said Neville, a member of the UO’s Institute of Neuroscience and director of the UO’s Brain Development Lab.
Children, she noted, often pick up grammar rules implicitly through routine daily interactions with parents or peers, simply hearing and processing new words and their usage before any formal instruction. She likened such learning to “Jabberwocky,” the nonsense poem introduced by writer Lewis Carroll in 1871 in “Through the Looking Glass,” where Alice discovers a book in an unrecognizable language that turns out to be written inversely and readable in a mirror.
For a second language, she said, “Teach grammatical rules implicitly, without any semantics at all, like with jabberwocky. Get them to listen to jabberwocky, like a child does.”
The pain sensations of others can be felt by some people, just by witnessing their agony, according to new research.
A Monash University study into the phenomenon known as somatic contagion found almost one in three people could feel pain when they see others experience pain. It identified two groups of people that were prone to this response - those who acquire it following trauma, injury such as amputation or chronic pain, and those with the condition present at birth, known as the congenital variant.
Presenting her findings at the Australian and New Zealand College of Anaesthetists’ annual scientific meeting in Melbourne earlier this week, Dr Melita Giummarra, from the School of Psychology and Psychiatry, said in some cases people suffered severe painful sensations in response to another person’s pain.
“My research is now beginning to differentiate between at least these two unique profiles of somatic contagion,” Dr Giummarra said.
“While the congenital variant appears to involve a blurring of the boundary between self and other, with heightened empathy, acquired somatic contagion involves reduced empathic concern for others, but increased personal distress.
“This suggests that the pain triggered corresponds to a focus on their own pain experience rather than that of others.”
Most people experience emotional discomfort when they witness pain in another person and neuroimaging studies have shown that this is linked to activation in the parts of the brain that are also involved in the personal experience of pain.
Dr Giummarra said for some people the pain they ‘absorb’ mirrors the location and site of the pain in another they are witnessing and is generally localised.
“We know that the same regions of the brain are activated for these groups of people as when they experience their own pain. First in emotional regions but then there is also sensory activation. It is a vicarious – it literally triggers their pain, Dr Giummarra said”
Dr Giummarra has developed a new tool to characterise the reactions people have to pain in others that is also sensitive to somatic contagion – the Empathy for Pain Scale.
These two very different tricks have the same effect; they delight and astound, leaving the audience to ponder (usually unsuccessfully):
How did they do that?
How could such a seemingly innocuous form of entertainment affect such diverse areas?
Uncovering magic’s secrets
In 1893, French psychologist Alfred Binet managed to co-opt five of the country’s most prominent magicians to help him understand illusions.
His interest in the development of cinema led him to record and view their performances frame by frame.
He was able to analyse the movement of the magicians as an animated sequence with the hope of understanding how audiences could be deceived by the magic performed right in front of them.
In his 1894 article La Psychologie de la Prestidigitation, Binet concluded that magical illusions were created by so many little optical tricks that:
to perceive them could be quite as difficult as to count with the naked eye the grains of sand on the seashore.
A 2008 article by a group of research psychologists argued that it was time to acknowledge magic’s influence on the cognitive sciences, opening a new field called the “science of magic”.
In 2010, neuroscientists Stephen Macknik and Susana Martinez-Conde coined the term “neuromagic” in their book Sleights of Mind.
The pair published some of their research findings in Nature, co-authored with not one, but four of the world’s leading magicians.
Like Binet more than a century before, they saw the value of working directly with magicians.
Magic has finally emerged from the box labelled “entertainment” and now shines a light on one of the most perplexing areas of mind studies – perception.
Perception is key in many magic techniques. Audience members will follow a magician’s hand when he or she gestures in a curved line – but not when the line is straight, to give just one example.
Scientific attempts to understand perceptual processes have largely relied on functional Magnetic Resonance Imaging (fMRI) – medical imaging techniques that identify brain activity through changes in its blood flow.
Scientists also study eye movements using head-mounted eye trackers to ascertain objects of visual focus.
But much of our visual perception cannot be understood as a direct fit between seeing something and that thing registering in our attention.
Looking but not seeing
Our everyday perception is littered with episodes that psychologists call “inattentional blindness” and “change blindness”.
In other words, something happens in front of us but because our attention is elsewhere, we don’t register having seen it.
If the change occurs abruptly, it’s called inattentional blindness.
But while the colour card changing “trick” and Simons and Chabris’ experiment aren’t technically magic tricks, magic provides an arena for observing how our visual perception is often at odds with the objects and events happening before our very eyes.
Misdirection is a standard technique of the magician’s palette and demonstrates the perceptual rift between looking at something and attending to it and it is this rift that fascinates neuroscientists and neuropsychologists.
Commonly thought to be about speed – isn’t the hand quicker than the eye? – misdirection is actually more about leading us to focus only on a particular area.
When a magician throws a ball into the air and it seemingly vanishes, the trick works because the audience is following the magician’s gaze – not his hand.
After really throwing the ball into the air numerous times and then simply performing the same movement in every way but without the ball, most people will see a ball fly into the air and disappear.
The magician has misdirected your gaze into following his and deployed a combination of inattentional and change blindness.
A neurological perspective
What we also learn from this neurologically is that implied movement stimulates brain functioning in much the same way as watching an actual movement.
That your gaze can differ from your attention is something that magicians have long exploited.
So now neurologists are looking to magic to help answer questions such as:
Why don’t we see always something right in front of us?
Why do our eyes more easily follow curved rather than straight gestures across space?
Magic, which has exploited such aspects of the visual for centuries, offers us a framework to explore perception in an intriguing way, and the potential for understanding our perceptual system by investigating how magic exploits its blindness and gaps is enormous.
It has become a sophisticated research method and field helping to create more intuitive human-computer interface designs and advance rehabilitation techniques for people physically impaired by neurological conditions like strokes.
It is even being used to study problems in social responsiveness across the autism spectrum.
All we need to do now is convince more magicians to give up their secrets – but how easy that will be remains to be seen.
Brain scans are increasingly able to reveal whether or not you believe you remember some person or event in your life. In a new study presented at a cognitive neuroscience meeting today, researchers used fMRI brain scans to detect whether a person recognized scenes from their own lives, as captured in some 45,000 images by digital cameras. The study is seeking to test the capabilities and limits of brain-based technology for detecting memories, a technique being considered for use in legal settings.
“The advancement and falling costs of fMRI, EEG, and other techniques will one day make it more practical for this type of evidence to show up in court,” says Francis Shen of the University of Minnesota Law School, who is chairing a session on neuroscience and the law at a meeting of the Cognitive Neuroscience Society (CNS) in San Francisco this week. “But technological advancement on its own doesn’t necessarily lead to use in the law.” But as the technology has advanced and as the legal system desires to use more empirical evidence, neuroscience and the law are intersecting more often than in previous decades.
In U.S. courts, neuroscientific evidence has been used largely in cases involving brain injury litigation or questions of impaired ability. In some cases outside the United States, however, courts have used brain-based evidence to check whether a person has memories of legally relevant events, such as a crime. New companies also are claiming to use brain scans to detect lies – although judges have not yet admitted this evidence in U.S. courts. These developments have rallied some in the neuroscience community to take a critical look at the promise and perils of such technology in addressing legal questions – working in partnership with legal scholars through efforts such as the MacArthur Foundation Research Network on Law and Neuroscience.
Recognizing your own memories
What inspired Anthony Wagner, a cognitive neuroscientist at Stanford University, to test fMRI uses for memory detection was a case in June 2008 in Mumbai, India, in which a judge cited EEG evidence as indicating that a murder suspect held knowledge about the crime that only the killer could possess. “It appeared that the brain data held considerable sway,” says Wagner, who points out that the methods used in that case have not been subject to extensive peer review.
Since then, Wagner and colleagues have conducted a number of experiments to test whether brain scans can be used to discriminate between stimuli that people perceive as old or new, as well as more objectively, whether or not they have previously encountered a particular person, place, or thing. To date, Wagner and colleagues have had success in the lab using fMRI-based analyses to determine whether someone recognizes a person or perceives them as unfamiliar, but not in determining whether in fact they have actually seen them before.
In a new study presented today, his team sought to take the experiments out of the lab and into the real world by outfitting participants with digital cameras around their necks that automatically took photos of the participants’ everyday experiences. Over a multi-week period, the cameras yielded 45,000 photos per participant.
Wagner’s team then took brief photo sequences of individual events from the participants’ lives and showed them to the participants in the fMRI scanner, along with photo sequences from other subjects as the control stimuli. The researchers analyzed their brain patterns to determine whether or not the participants were recognizing the sequences as their own. “We did quite well with most subjects, with a mean accuracy of 91% in discriminating between event sequences that the participant recognized as old and those that the participant perceived as unfamiliar, ” Wagner says. “These findings indicate that distributed patterns of brain activity, as measured with fMRI, carry considerable information about an individual’s subjective memory experience – that is, whether or not they are remembering the event.”
In another new study, Wagner and colleagues tested whether people can “beat the technology” by using countermeasures to alter their brain patterns. Back in the lab, the researchers showed participants individual faces and later asked them whether the faces were old or new. “Halfway through the memory test, we stopped and told them ‘What we are actually trying to do is read out from your brain patterns whether or not you are recognizing the face or perceiving it as novel, and we’ve been successful with other subjects in doing this in the past. Now we want you to try to beat the system by altering your neural responses.’” The researchers instructed the participants to think about a familiar person or experience when presented with a new face, and to focus on a novel feature of the face when presented a previously encountered face.
“In the first half of the test, during which participants were just making memory decisions, we were well above chance in decoding from brain patterns whether they recognized face or perceived it as novel. However, in the second half of the test, we were unable to classify whether or not they recognized the face nor whether the face was objectively old or new,” Wagner says. Within a forensic setting, Wagner says, it is conceivable that a suspect could use such measures to try to mask the brain patterns associated with memory.
Wagner says that his work to date suggests that the technology may have some utility in reading out brain patterns in cooperative individuals but that the uses are much more uncertain with uncooperative individuals. However, Wagner stresses that the method currently does not distinguish well between whether a person’s memory reflects true or false recognition. He says that it is premature to consider such evidence in the courts because many additional factors await future testing, including the effects of stress, practice, and time between the experience and the memory test.
Overgeneralizing the adolescent brain
A general challenge to the use of neuroscientific evidence in legal settings, Wagner says, is that most studies are at the group rather than the individual level. “The law cares about a particular individual in a particular situation right in front of them,” he says, and the science often cannot speak to that specificity.
Shen cites the challenge of making individualized inference from group-based data as one of the major ones facing use of neuroscience evidence in the court. “This issue has come up in the context of juvenile justice, where the adolescent brain development data confirms behavioral data that on average 17-year-olds are more impulsive than adults, but does not tell us whether a particular 17-year-old, namely the one on trial, was less able to control his/her actions on the day and in the manner in question,” he says.
Indeed, B.J. Casey of the Weill Medical College of Cornell University says that too often we overgeneralize the lack of self control among adolescents. Although adolescents do show poor self control as a group, some situations and individuals are more prone to this breakdown than others.
“It is not that teens can’t make decisions, they can and they can do so efficiently,” Casey says. “It is when they must make decisions in the heat of the moment – in presence of potential or perceived threats, among peers – that the court should consider diminished responsibility of teens while still holding them accountable for their behavior.” Research suggests that this diminished ability is due to the immature development of circuitry involved in processing of negative or positive cues in the environment in the subcortical limbic regions and then in regulating responses to those cues in the prefrontal cortex.
The body of research to date is at the group-level, however, and is not yet able to comment on the neurobiological maturity of an individual adolescent. To help provide more guidance on this issue in legal settings, Casey and colleagues are working alongside legal scholars on a developmental imaging study, funded by the MacArthur Foundation, that is examining behaviors relevant to juvenile criminal behavior, including impulsivity and peer influence.
Making real-world connections
The same type of work – to connect brain imaging to particular behaviors in the real-world – is ongoing in a number of other areas, including fMRI-based lie detection and linking negligence to specific mental states. “It’s a big leap to go from a laboratory setting, in which impulse control may be measured by one’s ability to not press a button in response to a stimulus, to the real-world, where the question is whether someone had requisite self-control not to tie up an innocent person and throw them off a bridge.” Shen says. “I don’t see neuroscience solving these big problems anytime soon, and so the question for law becomes: What do we do with this uncertainty? I think this is where we’re at right now, and where we’ll be for some time.”
“With a few notable exceptions such as death penalty cases, cases where a juvenile is facing a very stiff sentence, and litigating brain injury claims, ‘law and neuroscience’ is not familiar to most lawyers,” Shen says. “But this might change – and soon.” The ongoing work is vital, he says, for laying a foundation for a future that’s yet to come, and he hopes that more neuroscientists will increasingly collaborate with legal scholars.
UK scientists have embarked on a six-year project to map how nerve connections develop in babies’ brains while still in the womb and after birth.
By the time a baby takes its first breath many of the key pathways between nerves have already been made. And some of these will help determine how a baby thinks or sees the world, and may have a role to play in the development of conditions such as autism, scientists say.
But how this rich neural network assembles in the baby before birth is relatively unchartered territory.
Researchers from Guy’s and St Thomas’ Hospital, King’s College London, Imperial College and Oxford University aim to produce a dynamic wiring diagram of how the brain grows, at a level of detail that they say has been impossible until now.
They hope that by charting the journeys of bundles of nerves in the final three months of pregnancy, doctors will be able to understand more about how they can help in situations when this process goes wrong.
Prof David Edwards, director of the Centre for the Developing Brain, who is leading the research, says: “There is a distressing number of children in our society who grow up with problems because of things that happen to them around the time of birth or just before birth.
“It is very important to be able to scan babies before they are born, because we can capture a period when an awful lot is changing inside the brain, and it is a time when a great many of the things that might be going wrong do seem to be going wrong.”
The study - known as the Developing Human Connectome Project - hopes to look at more than 1,500 babies, studying many aspects of their neurological development.
By examining the brains of babies while they are still growing in the womb, as well as those born prematurely and at full term, the scientists will try to define baselines of normal development and investigate how these may be affected by problems around birth.
And they plan to share their map with the wider research community.
Central to this project are advanced MRI scanning techniques, which the scientists say are able to pick up on details of the growing brain that have been difficult to capture until now.
While in the womb, foetuses are free to somersault in their amniotic sacs, and this constant movement has so far hindered clear images of growing brains.
But researchers at the Centre for the Developing Brain have found ways to counter the effects of these movements, building up full three-dimensional pictures while the foetus is in motion.
And by placing the MRI machine in the neonatal intensive care unit at Evelina Children’s Hospital in London they are one of the few centres in the world to have a scanner in such close proximity to the babies who often need it most, Prof Edwards says.
This means the same scanning system can be used to find out more about the brains of the sickest and smallest newborn babies, he says.
Daniel Rueckert, professor of visual information processing at Imperial College London, who is also involved in the research, says: “We are trying to look at brain connectivity in two ways: firstly, from a structural perspective, to find out which parts of the brain are wired to other parts. And secondly we are looking at functional connectivity - how strongly two brain regions are linked across time and activity.”
But Prof Partha Mitra, a neuroscientist at Cold Spring Harbor Laboratory, New York state, says we need to be aware of the limitations of the technology in use.
“It would obviously be a very good thing to know more about the circuits in the developing human brain. Much of what we know hasn’t changed in a hundred years and has come from dissection studies.
“But we need to keep in mind the imaging techniques we have are indirect - we can’t open up a human brain and look at the connections while someone is alive so we rely on these non-invasive methods. But there is a big gap between the real circuits in the brain and what images can show us.”
Prof Rueckert acknowledges that this map will provide a “macro-level” view of the developing brain and not be the “final answer”.
But he points to early results from the adult version of this project - the Human Connectome Project, based in the US: “There is so much evidence already from the adult project that there are significant changes in the brain that can be mapped with the technology we have now.
“It will be incredibly useful to be able to do this with the still growing and developing brain - perhaps giving us more time to intervene when things go wrong.”
Building on their history of innovative brain-imaging techniques, scientists at the U.S. Department of Energy’s Brookhaven National Laboratory and collaborators have developed a new way to use light and chemistry to map brain activity in fully-awake, moving animals. The technique employs light-activated proteins to stimulate particular brain cells and positron emission tomography (PET) scans to trace the effects of that site-specific stimulation throughout the entire brain. As described in a paper published online today in the Journal of Neuroscience, the method will allow researchers to map exactly which downstream neurological pathways are activated or deactivated by stimulation of targeted brain regions, and how that brain activity correlates with particular behaviors and/or disease conditions.
“This technique gives us a new way to look at the function of specific brain cells and map which brain circuits are active in a wide range of neuropsychiatric diseases — from depression to Parkinson’s disease, neurodegenerative disorders, and drug addiction — and also to monitor the effects of various treatments,” said the paper’s lead author, Panayotis (Peter) Thanos, a neuroscientist and director of the Behavioral Neuropharmacology and Neuroimaging Section — part of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) Laboratory of Neuroimaging at Brookhaven Lab — and a professor at Stony Brook University. “Because the animals are awake and able to move during stimulation, we can also directly study how their behavior correlates with brain activity,” he said.
The new brain-mapping method combines very recent advances in a field known as “optogenetics” — the use of optics (light activation) and genetics (genetically coded light-sensitive proteins) to control the activity of individual neurons, or nerve cells — and Brookhaven’s historical development of radioactively labeled chemical tracers to track biological activity with PET scanners.
The scientists used a modified virus to deliver a light-sensitive protein to particular brain cells in rats. Genetic coding can deliver the protein to specifically targeted brain-cell receptors. Then, after stimulating those proteins with light shone through an optical fiber inserted through a tiny tube called a cannula, they monitored overall brain activity using a radiotracer known as 18FDG, which serves as a stand-in for glucose, the body’s (and brain’s) main source of energy.
The unique chemistry of 18FDG causes it to be temporarily “trapped” inside cells that are hungry for glucose — those activated by the brain stimulation — and remain there long enough for the detectors of a PET scanner to pick up the radioactive signal, even after the animals are anesthetized to ensure they stay still for scanning. But because the animals were awake and moving when the tracer was injected and the brain cells were being stimulated, the scans reveal what parts of the brain were activated (or deactivated) under those conditions, giving scientists important information about how those brain circuits function and correlate with the animals’ behaviors.
“In this paper, we wanted to stimulate the nucleus accumbens, a key part of the brain involved in reward that is very important to understanding drug addiction,” Thanos said. “We wanted to activate the cells in that area and see which brain circuits were activated and deactivated in response.”
The scientists used the technique to trace activation and deactivation in number of key pathways, and confirmed their results with other analysis techniques.
The method can reveal even more precise effects.
“If we want to know more about the role played by specific types of receptors — say the dopamine D1 or D2 receptors involved in processing reward — we could tailor the light-sensitive protein probe to specifically stimulate one or the other to tease out those effects,” he said.
Another important aspect is that the technique does not require the scientists to identify in advance the regions of the brain they want to investigate, but instead provides candidate brain regions involved anywhere in the brain – even regions not well understood.
“We look at the whole brain,” Thanos said. “We take the PET images and co-register them with anatomical maps produced with magnetic resonance imaging (MRI), and use statistical techniques to do comparisons voxel by voxel. That allows us to identify which areas are more or less activated under the conditions we are exploring without any prior bias about what regions should be showing effects.”
After they see a statistically significant effect, they use the MRI maps to identify the locations of those particular voxels to see what brain regions they are in.
“This opens it up to seeing an effect in any region in the brain — even parts where you would not expect or think to look — which could be a key to new discoveries,” he said.
Today the White House announced its goal to fund Brain Research, in hopes of furthering understanding of brain disorders and degenerative diseases such as Alzheimer’s.
Two years ago Scientific American magazine sent me to the University of Texas at Austin to borrow a human brain. They needed me to photograph a normal, adult, non-dissected brain that the university had obtained by trading a syphilitic lung with another institution. The specimen was waiting for me, but before I left they asked if I’d like to see their collection.
I walked into a storage closet filled with approximately one-hundred human brains, none of them normal, taken from patients at the Texas State Mental Hospital. The brains sat in large jars of fluid, each labeled with a date of death or autopsy, a brief description in Latin, and a case number. These case numbers corresponded to micro film held by the State Hospital detailing medical histories. But somehow, regardless of how amazing and fascinating this collection was, it had been largely untouched, and unstudied for nearly three decades.
Driving back to my studio with a brain snugly belted into the passenger seat, I quickly became obsessed with the idea of photographing the collection, preserving the already decaying brains, and corresponding the images to their medical histories. I met with my friend Alex Hannaford, a features journalist, to help me find the collection’s history dating back to the 1950s.
Over the past year while working this idea into a book, we’ve learned how heavily storied the collection is. That it was originally intended to be displayed and studied, but without funding it instead stagnated. And that the microfilm histories of each brain had been destroyed years ago.
My original vision of a photo book accompanied by medical data and a comprehensive essay turned into a story of loss and neglect. But Alex continued to pursue some scientific hope for the collection. After discussions with various neuroscientists we learned that through MRI technology and special techniques in DNA scanning there is still hope. And with the new possibilities of federal brain research funding, this collection’s secrets may yet be unlocked.
As we begin the hunt for someone to publish my 230 images accompanied by Alex’s 14,000 word essay, the University has found new interest in the collection. They currently are planning to make MRI scans of the brains.