Posts tagged brain scans
Articles and news from the latest research reports.
Optical brain scanner goes where other brain scanners can’t
Scientists have advanced a brain-scanning technology that tracks what the brain is doing by shining dozens of tiny LED lights on the head. This new generation of neuroimaging compares favorably to other approaches but avoids the radiation exposure and bulky magnets the others require, according to new research at Washington University School of Medicine in St. Louis.
The new optical approach to brain scanning is ideally suited for children and for patients with electronic implants, such as pacemakers, cochlear implants and deep brain stimulators (used to treat Parkinson’s disease). The magnetic fields in magnetic resonance imaging (MRI) often disrupt either the function or safety of implanted electrical devices, whereas there is no interference with the optical technique.
The new technology is called diffuse optical tomography (DOT). While researchers have been developing it for more than 10 years, the method had been limited to small regions of the brain. The new DOT instrument covers two-thirds of the head and for the first time can image brain processes taking place in multiple regions and brain networks such as those involved in language processing and self-reflection (daydreaming).
The results are now available online in Nature Photonics.
“When the neuronal activity of a region in the brain increases, highly oxygenated blood flows to the parts of the brain doing more work, and we can detect that,” said senior author Joseph Culver, PhD, associate professor of radiology. “It’s roughly akin to spotting the rush of blood to someone’s cheeks when they blush.”
The technique works by detecting light transmitted through the head and capturing the dynamic changes in the colors of the brain tissue.
Although DOT technology now is used in research settings, it has the potential to be helpful in many medical scenarios as a surrogate for functional MRI, the most commonly used imaging method for mapping human brain function. Functional MRI also tracks activity in the brain via changes in blood flow. In addition to greatly adding to our understanding of the human brain, fMRI is used to diagnose and monitor brain disease and therapy.
Another commonly used method for mapping brain function is positron emission tomography (PET), which involves radiation exposure. Because DOT technology does not use radiation, multiple scans performed over time could be used to monitor the progress of patients treated for brain injuries, developmental disorders such as autism, neurodegenerative disorders such as Parkinson’s, and other diseases.
Unlike fMRI and PET, DOT technology is designed to be portable, so it could be used at a patient’s beside or in the operating room.
“With the new improvements in image quality, DOT is moving significantly closer to the resolution and positional accuracy of fMRI,” said first author Adam T. Eggebrecht, PhD, a postdoctoral research fellow. “That means DOT can be used as a stronger surrogate in situations where fMRI cannot be used.”
The researchers have many ideas for applying DOT, including learning more about how deep brain stimulation helps Parkinson’s patients, imaging the brain during social interactions, and studying what happens to the brain during general anesthesia and when the heart is temporarily stopped during cardiac surgery.
For the current study, the researchers validated the performance of DOT by comparing its results to fMRI scans. Data was collected using the same subjects, and the DOT and fMRI images were aligned. They looked for Broca’s area, a key area of the frontal lobe used for language and speech production. The overlap between the brain region identified as Broca’s area by DOT data and by fMRI scans was about 75 percent.
In a second set of tests, researchers used DOT and fMRI to detect brain networks that are active when subjects are resting or daydreaming. Researchers’ interests in these networks have grown enormously over the past decade as the networks have been tied to many different aspects of brain health and sickness, such as schizophrenia, autism and Alzheimer’s disease. In these studies, the DOT data also showed remarkable similarity to fMRI — picking out the same cluster of three regions in both hemispheres.
“With the improved image quality of the new DOT system, we are getting much closer to the accuracy of fMRI,” Culver said. “We’ve achieved a level of detail that, going forward, could make optical neuroimaging much more useful in research and the clinic.”
While DOT doesn’t let scientists peer very deeply into the brain, researchers can get reliable data to a depth of about one centimeter of tissue. That centimeter contains some of the brain’s most important and interesting areas with many higher brain functions, such as memory, language and self-awareness represented.
During DOT scans, the subject wears a cap composed of many light sources and sensors connected to cables. The full-scale DOT unit takes up an area slightly larger than an old-fashioned phone booth, but Culver and his colleagues have built versions of the scanner mounted on wheeled carts. They continue to work to make the technology more portable.
Low-fat diet helps fatigue in people with MS
People with multiple sclerosis who for one year followed a plant-based diet very low in saturated fat had much less MS-related fatigue at the end of that year — and significantly less fatigue than a control group of people with MS who didn’t follow the diet, according to an Oregon Health & Science University study being presented today at the American Academy of Neurology’s annual meeting in Philadelphia, Pa.
The study was the first randomized-controlled trial to examine the potential benefits of the low fat diet on the management of MS. The study found no significant differences between the two groups in brain lesions detected on MRI brain scans or on other measures of MS. But while the number of trial participants was relatively small, study leaders believe the significantly improved fatigue symptoms merited further and larger studies of the diet.
"Fatigue can be a debilitating problem for many people living with relapsing-remitting MS," said Vijayshree Yadav, M.D., an associate professor of neurology in the OHSU School of Medicine and clinical medical director of the OHSU Multiple Sclerosis Center. "So this study’s results — showing some notable improvement in fatigue for people who follow this diet — are a hopeful hint of something that could help many people with MS."
The study investigated the effects of following a diet called the McDougall Diet, devised by John McDougall, M.D. The diet is partly based on an MS-fighting diet developed in the 1940s and 1950s by the late Roy Swank, M.D., a former head of the division of neurology at OHSU. The McDougall diet, very low in saturated fat, focuses on eating starches, fruits and vegetables and does not include meat, fish or dairy products.
The study, which began in 2008, looked at the diet’s effect on the most common form of MS, called relapsing-remitting MS. About 85 percent of people with MS have relapsing-remitting MS, characterized by clearly defined attacks of worsening neurological function followed by recovery periods when symptoms improve partially or completely.
The study measured indicators of MS among a group of people who followed the McDougall Diet for 12 months and a control group that did not. The study measured a range of MS indicators and symptoms, including brain lesions on MRI brain scans of study participants, relapse rate, disabilities caused by the disease, body weight and cholesterol levels.
It found no difference between the diet group and the control group in the number of MS-caused brain lesions detected on the MRI scans. It also found no difference between the two groups in relapse rate or level of disability caused by the disease. People who followed the diet did lose significantly more weight than the control group and had significantly lower cholesterol levels. People who followed the diet also had higher scores on a questionnaire that measured their quality of life and overall mood.
The study’s sample size was relatively small. Fifty-three people completed the study, with 27 in the control group and 22 people in the diet group who complied with the diet’s restrictions.
"This study showed the low-fat diet might offer some promising help with the fatigue that often comes with MS," said Dennis Bourdette, M.D., F.A.A.N., chair of OHSU’s Department of Neurology, director of OHSU’s MS Center and a study co-author. "But further study is needed, hopefully with a larger trial where we can more closely look at how the diet might help fatigue and possibly affect other symptoms of MS."
(Source: eurekalert.org)
Brain scans show what makes us drink water and what makes us stop drinking
Drinking water when you’re thirsty is a pleasurable experience. Continuing to drink when you’re not, however, can be very unpleasant. To understand why your reaction to water drinking changes as your thirst level changes, Pascal Saker of the University of Melbourne and his colleagues performed fMRI scans on people as they drank water. They found that regions of the brain associated with positive feelings became active when the subjects were thirsty, while regions associated with negative feelings and with controlling and coordinating movement became active after the subjects were satiated. The research appears in the Proceedings of the National Academy of Sciences.
Brain Scans Show We Take Risks Because We Can’t Stop Ourselves
A new study correlating brain activity with how people make decisions suggests that when individuals engage in risky behavior, such as drunk driving or unsafe sex, it’s probably not because their brains’ desire systems are too active, but because their self-control systems are not active enough.
This might have implications for how health experts treat mental illness and addiction or how the legal system assesses a criminal’s likelihood of committing another crime.
Researchers from The University of Texas at Austin, UCLA and elsewhere analyzed data from 108 subjects who sat in a magnetic resonance imaging (MRI) scanner — a machine that allows researchers to pinpoint brain activity in vivid, three-dimensional images — while playing a video game that simulates risk-taking.
The researchers used specialized software to look for patterns of activity across the whole brain that preceded a person’s making a risky choice or a safe choice in one set of subjects. Then they asked the software to predict what other subjects would choose during the game based solely on their brain activity. The software accurately predicted people’s choices 71 percent of the time.
“These patterns are reliable enough that not only can we predict what will happen in an additional test on the same person, but on people we haven’t seen before,” said Russell Poldrack, director of UT Austin’s Imaging Research Center and professor of psychology and neuroscience.
When the researchers trained their software on much smaller regions of the brain, they found that just analyzing the regions typically involved in executive functions such as control, working memory and attention was enough to predict a person’s future choices. Therefore, the researchers concluded, when we make risky choices, it is primarily because of the failure of our control systems to stop us.
“We all have these desires, but whether we act on them is a function of control,” said Sarah Helfinstein, a postdoctoral researcher at UT Austin and lead author of the study that appears online this week in the journal Proceedings of the National Academy of Sciences.
Helfinstein said that additional research could focus on how external factors, such as peer pressure, lack of sleep or hunger, weaken the activity of our brains’ control systems when we contemplate risky decisions.
“If we can figure out the factors in the world that influence the brain, we can draw conclusions about what actions are best at helping people resist risks,” said Helfinstein.
To simulate features of real-world risk-taking, the researchers used a video game called the Balloon Analogue Risk Task (BART) that past research has shown correlates well with self-reported risk-taking such as drug and alcohol use, smoking, gambling, driving without a seatbelt, stealing and engaging in unprotected sex.
While playing the BART, the subject sees a balloon on the screen and is asked to make either a risky choice (inflate the balloon a little and earn a few cents) or a safe choice (stop the round and “cash out,” keeping whatever money was earned up to that point). Sometimes inflating the balloon causes it to burst and the player loses all the cash earned from that round. After each successful balloon inflation, the game continues with the chance of earning another standard-sized reward or losing an increasingly large amount. Many health-relevant risky decisions share this same structure, such as when deciding how many alcoholic beverages to drink before driving home or how much one can experiment with drugs or cigarettes before developing an addiction.
The data for this study came from the Consortium for Neuropsychiatric Phenomics at UCLA, which recruited adults from the Los Angeles area for researchers to examine differences in response inhibition and working memory between healthy adults and patients diagnosed with bipolar disorder, schizophrenia, or adult attention deficit hyperactivity disorder (ADHD). Only data collected from healthy participants were included in the present analyses.
Computer can read letters directly from the brain
By analysing MRI images of the brain with an elegant mathematical model, it is possible to reconstruct thoughts more accurately than ever before. In this way, researchers from Radboud University Nijmegen have succeeded in determining which letter a test subject was looking at. The journal Neuroimage has accepted the article, which will be published soon. A preliminary version of the article can be read online.
Functional MRI scanners have been used in cognition research primarily to determine which brain areas are active while test subjects perform a specific task. The question is simple: is a particular brain region on or off? A research group at the Donders Institute for Brain, Cognition and Behaviour at Radboud University has gone a step further: they have used data from the scanner to determine what a test subject is looking at. The researchers ‘taught’ a model how small volumes of 2x2x2 mm from the brain scans - known as voxels - respond to individual pixels. By combining all the information about the pixels from the voxels, it became possible to reconstruct the image viewed by the subject. The result was not a clear image, but a somewhat fuzzy speckle pattern. In this study, the researchers used hand-written letters.
Prior knowledge improves model performance
‘After this we did something new’, says lead researcher Marcel van Gerven. ‘We gave the model prior knowledge: we taught it what letters look like. This improved the recognition of the letters enormously. The model compares the letters to determine which one corresponds most exactly with the speckle image, and then pushes the results of the image towards that letter. The result was the actual letter, a true reconstruction.’
‘Our approach is similar to how we believe the brain itself combines prior knowledge with sensory information. For example, you can recognise the lines and curves in this article as letters only after you have learned to read. And this is exactly what we are looking for: models that show what is happening in the brain in a realistic fashion. We hope to improve the models to such an extent that we can also apply them to the working memory or to subjective experiences such as dreams or visualisations. Reconstructions indicate whether the model you have created approaches reality.’
Improved resolution; more possibilities
‘In our further research we will be working with a more powerful MRI scanner,’ explains Sanne Schoenmakers, who is working on a thesis about decoding thoughts. ‘Due to the higher resolution of the scanner, we hope to be able to link the model to more detailed images. We are currently linking images of letters to 1200 voxels in the brain; with the more powerful scanner we will link images of faces to 15,000 voxels.’
Brain scans could predict response to antipsychotic medication
Researchers from King’s College London and the University of Nottingham have identified neuroimaging markers in the brain which could help predict whether people with psychosis respond to antipsychotic medications or not.
In approximately half of young people experiencing their first episode of a psychosis (FEP), the symptoms do not improve considerably with the initial medication prescribed, increasing the risk of subsequent episodes and worse outcome. Identifying individuals at greatest risk of not responding to existing medications could help in the search for improved medications, and may eventually help clinicians personalize treatment plans.
In a study published today in JAMA Psychiatry, researchers used structural Magnetic Resonance Imaging (MRI) to scan the brains of 126 individuals – 80 presenting with FEP, and 46 healthy controls. Participants had an MRI scan shortly after their FEP, and another assessment 12 weeks later, to establish whether symptoms had improved following the first treatment with antipsychotic medications.
The researchers examined a particular feature of the brain called “cortical gyrification” - the extent of folding of the cerebral cortex and a marker of how it has developed. They found that the individuals who did not respond to treatment already had a significant reduction in gyrification across multiple brain regions, compared to patients who did respond and to individuals without psychosis. This reduced gyrification was particularly present in brain areas considered important in psychosis, such as the temporal and frontal lobes. Those who responded to treatment were virtually indistinguishable from the healthy controls.
The researchers also investigated whether the differences could be explained by the type of diagnosis of psychosis (eg. with or without affective symptoms, such as depression or elated mood). They found that reduced gyrification predicted non-response to treatment independently of the diagnosis.
Dr Paola Dazzan from the Department of Psychosis Studies at King’s College London’s Institute of Psychiatry, and senior author of the paper, says: “Our study provides crucial evidence of a neuroimaging marker that, if validated, could be used early in psychosis to help identify those people less likely to respond to medications. It is possible that the alterations we observed are due to differences in the way the brain has developed early on in people who do not respond to medication compared to those who do.”
She continues:”There have been few advances in developing novel anti-psychotic drugs over the past 50 years and we still face the same problems with a sub-group of people who do not respond to the drugs we currently use. We could envisage using a marker like this one to identify people who are least likely to respond to existing medications and focus our efforts on developing new medication specifically adapted to this group. In the longer term, if we were able to identify poor responders at the outset, we may be able to formulate personalized treatment plans for that individual patient.”
Dr Lena Palaniyappan from the University of Nottingham adds: “All of us have complex and varying patterns of folding in our brains. For the first time we are showing that the measurement of these variations could potentially guide us in treating psychosis. It is possible that people with specific patterns of brain structure respond better to treatments other than antipsychotics that are currently in use. Clearly, the time is ripe for us to focus on utilising neuroimaging to guide treatment decisions.”
Psychosis is a term used to indicate mental health disorders that present with symptoms like hallucinations (such as hearing voices) or delusions (unshakeable beliefs based on the person’s altered perception of reality, which may not correspond to the way others see the world). Psychotic episodes are present in conditions such as schizophrenia and bipolar disorder.
Approximately 1 in 100 people in England have at least one episode of psychosis throughout their lives. In most cases, psychosis develops during late adolescence (15 or above) or adulthood. Treatment involves a combination of antipsychotic medication, psychological therapies and social support. Many people with psychosis go on to lead ordinary lives and for about 60% of people, the symptoms disappear within 12 months from onset. However, for others, treatment is less straightforward and many do not respond to the initial antipsychotic treatment prescribed by their doctor. Early response to antipsychotic medication is known to be associated with better outcome and fewer subsequent episodes, and intervening early with effective treatments is therefore important.
(Source: kcl.ac.uk)
Centers throughout the brain work together to make reading possible
A combination of brain scans and reading tests has revealed that several regions in the brain are responsible for allowing humans to read.
The findings open up the possibility that individuals who have difficulty reading may only need additional training for specific parts of the brain — targeted therapies that could more directly address their individual weaknesses.
“Reading is a complex task. No single part of the brain can do all the work,” said Qinghua He, postdoctoral research associate at the USC Brain and Creativity Institute, based at the USC Dornsife College of Letters, Arts and Sciences, and first author of a study on this research that was published in The Journal of Neuroscience on July 31.
The study looked at the correlation between reading ability and brain structure revealed by high-resolution magnetic resonance imaging (MRI) scans of more than 200 participants.
To control for external factors, the participants were about the same age and education level (college students); right-handed (lefties use the opposite hemisphere of their brain for reading); and all had about the same language skills (Chinese-speaking, with English as a second language for more than nine years). Their IQ, response speed and memory were also tested.
The study first collected data for seven different reading tests of a sample of more than 400 participants. These tests were intended to explore three aspects of their reading ability: phonological decoding ability (the ability to sound out printed words); form-sound association (how well participants could make connections between a new word and sound); and naming speed (how quickly participants were able to read out loud).
Each of these aspects, it turned out, was related to the gray matter volume — the amount of neurons — in different parts of the brain.
The MRI analysis showed that phonological decoding ability was strongly connected with gray matter volume in the left superior parietal lobe (around the top/rear of the brain); form-sound association was strongly connected with the hippocampus and cerebellum; and naming speed lit up a variety of locations around the brain.
“Our results strongly suggest that reading consists of unique capacities and is supported by distinct neural systems that are relatively independent of general cognitive abilities,” said Gui Xue, corresponding author of the study. Xue was formerly a research assistant professor at USC and now is a professor and director of the Center for Brain and Learning Sciences at Beijing Normal University.
“Although there is no doubt that reading has to build up existing neural systems due to the short history of written language in human evolution, years of reading experiences might have finely tuned the system to accommodate the specific requirement of a given written system,” Xue said.
He and Xue collaborated with Chunhui Chen and Qi Dong of Beijing Normal University; Chuansheng Chen of the University of California, Irvine; and Zhong-Lin Lu of Ohio State University.
One of the top features of this study was its unusually wide sample size, according to researchers. Typically, MRI studies test a relatively small sample of individuals — perhaps around 20 to 30 — because of the high cost of using the MRI machine. Testing a single individual can cost about $500, depending on the nature of the research.
The team had the good fortune of receiving access to Beijing Normal University’s new MRI center — the BNU Imaging Center for Brain Research — just before it opened to the public. With support from several grants, the researchers were able to conduct MRI tests on 233 individuals.
Next, the group will explore how to combine data from other factors, such as white matter, resting and task functional MRI, as well as more powerful machine-learning techniques, to improve the accuracy of individuals’ reading abilities.
“Research along this line will enable the early diagnosis of reading difficulties and the development of more targeted therapies,” Xue said.
Could the Government Get a Search Warrant for Your Thoughts?
We don’t have a mind reading machine. But what if we one day did? The technique of functional MRI (fMRI), which measures changes in localized brain activity over time, can now be used to infer information regarding who we are thinking about, what we have seen, and the memories we are recalling. As the technology for inferring thought from brain activity continues to improve, the legal questions regarding its potential application in criminal and civil trials are gaining greater attention.
Last year, a Maryland man on trial for murdering his roommate tried to introduce results from an fMRI-based lie detection test to bolster his claim that the death was a suicide. The court ruled (PDF) the test results inadmissible, noting that the “fMRI lie detection method of testing is not yet accepted in the scientific community.” In a decision last year to exclude fMRI lie detection test results submitted by a defendant in a different case, the Sixth Circuit was even more skeptical, writing (PDF) that “there are concerns with not only whether fMRI lie detection of ‘real lies’ has been tested but whether it can be tested.”
So far, concerns regarding reliability have kept thought-inferring brain measurements out of U.S. (but not foreign) courtrooms. But is technology the only barrier? Or, if more mature, reliable brain scanning methods for detecting truthfulness and reading thoughts are developed in the future, could they be employed not only by defendants hoping to demonstrate innocence but also by prosecutors attempting to establish guilt? Could prosecutors armed with a search warrant compel an unwilling suspect to submit to brain scans aimed at exploring his or her innermost thoughts?
The answer surely ought to be no. But getting to that answer isn’t as straightforward as it might seem. The central constitutional question relates to the Fifth Amendment, which states that “no person … shall be compelled in any criminal case to be a witness against himself.” In interpreting the Fifth Amendment, courts have distinguished between testimonial evidence, which is protected from compelled self-incriminating disclosure, and physical evidence, which is not. A suspected bank robber cannot refuse to participate in a lineup or provide fingerprints. But he or she can decline to answer a detective who asks, “Did you rob the bank last week?”
So is the information in a brain scan physical or testimonial? In some respects, it’s a mix of both. As Dov Fox wrote in a 2009 law review article, “Brain imaging is difficult to classify because it promises distinctly testimonial-like information about the content of a person’s mind that is packaged in demonstrably physical-like form, either as blood flows in the case of fMRI, or as brainwaves in the case of EEG.” Fox goes on to conclude that the compelled use of brain imaging techniques would “deprive individuals of control over their thoughts” and be a violation of the Fifth Amendment.
But there is an alternative view as well, under which the Fifth Amendment protects only testimonial communication, leaving the unexpressed thoughts in a suspect’s head potentially open to government discovery, technology permitting. In a recent law review article titled “A Modest Defense of Mind Reading,” Kiel Brennan-Marquez writes that “at least some mind-reading devices almost certainly would not” elicit “communicative acts” by the suspect, “making their use permissible under the Fifth Amendment.” Brennan-Marquez acknowledges that compelled mind-reading would raise privacy concerns, but argues that those should be addressed by the Fourth Amendment, which prohibits unreasonable searches and seizures.
That doesn’t seem right. It would make little sense to provide constitutional protection to a suspected bank robber’s refusal to answer a detective’s question if the thoughts preceding the refusal—e.g., “since I’m guilty, I’d better not answer this question”—are left unprotected. Stated another way, the right to remain silent would be meaningless if not accompanied by protection for the thinking required to exercise it.
And if that weren’t enough, concluding that compelled brain scans don’t violate the Fifth Amendment would raise another problem as well: In a future that might include mature mind-reading technology, it would leave the Fourth Amendment as the last barrier protecting our thoughts from unwanted discovery. That, in turn, would raise the possibility that the government could get a search warrant for our thoughts. It’s a chilling prospect, and one that we should hope never comes to pass.
![The Search for the Best Depression Treatment
Brain scans, blood samples, and other diagnostic tests could one day direct doctors to the best treatments for depression patients and uncover the biological basis of the condition.
When someone is diagnosed with depression, patient and doctor often begin a long trial-and-error process of testing different treatments. Sometimes they work, sometimes they don’t, so patients may try several options before finding the best one. But in the future, a brain scan, blood test, or some combination could help guide doctors to the best drugs, or lead them to suggest talk therapy.
Recently, Emory University researcher Helen Mayberg reported that a PET scan, a commonly used imaging method, can reveal whether a patient will respond better to an antidepressant or cognitive behavioral therapy. And in May, Medscape reported that David Mischoulon of Massachusetts General Hospital presented findings that the amount of a particular protein in the blood of depression patients could indicate whether a patient would do better by adding a form of folic acid to his or her treatment.
A key goal of such research is to distinguish between causes of depression. “The presence of certain biomarkers might give us a clue whether [a particular patient’s] depression is truly biologically driven, or whether it is depression like sadness over an event,” says Mischoulon. “If we can identify people who have these biological bases, it might suggest these patients might do better with medications, as opposed to psychotherapies or meditation.”
According to the World Health Organization, depression is the leading cause of disability globally. Many people do not seek or do not have access to treatment, and among those who do, fewer than 40 percent of depression patients improve with the first type of treatment they try. The problem is not that treatments like antidepressants and cognitive behavioral therapy don’t work, it’s that no one treatment works for every patient. Researchers from many disciplines, from neuroscience to genomics, are studying this complex disorder, which likely represents many different conditions with unique origins and treatments. Large clinical trials to predict a patient’s response to therapy or drugs based on brain or body biomarkers could improve treatment for future patients and perhaps uncover a clearer understanding of depression’s origins.
“You see now a number of big studies on predictive biomarkers,” says Mayberg, who has pioneered pacemaker-like implants as a treatment for severe cases of depression. She’s also involved in a large study of patients who will be treated with antidepressants or cognitive behavioral therapy based on brain scans. “It’s going to be interesting over the next year or two to see how this plays out,” she says. One question will be whether researchers will be able to identify markers that are both unambiguous but also practical to test. Brain scans may be the best place to start, she says, because they focus on the origin of the condition, but once good biomarkers are identified via brain scan, surrogates found in the blood may provide a simpler and more affordable option.
One challenge for researchers is that depression is probably a conglomeration of many diseases, says Madhukar Trivedi, a University of Texas Southwestern researcher heading a large trial that is trying to distinguish patients who respond better to one type of antidepressant compared to another. “There are a lot of subtypes in depression, so any given marker, whether genetic, protein, imaging, or EEG, ends up accounting for only a small percentage of variance for any group of patients,” says Trivedi.
If these researchers are successful, they could dramatically change how depression is treated and perhaps diagnosed. Doctors in the United States use the Diagnostic and Statistical Manual of Mental Disorders, or DSM, to diagnose depression. The diagnoses are largely based on the collection of symptoms presented or described by patients. In May, the head of the National Institute of Mental Health, Thomas Insel, announced that his institution would focus its research in areas other than the categories presented by the DSM. “Patients with mental disorders deserve better,” he said.
Bruce Cuthbert is heading the NIMH’s project to establish new ways of studying mental illness and potentially to improve future versions of the DSM by more precisely identifying the brain abnormalities in various diseases, including depression. The idea behind the project is to map out the genetic, circuit, and cognitive aspects of mental illness and to focus on individual features of disorders instead of clinical diagnoses. It could provide the information necessary to improve the DSM so that it is based on neuroscience and not just collections of symptoms. “In the future, we might define the disorders differently, or we might not. But this project will provide a framework to look at neural systems and how they operate and how that contributes to disease,” says Cuthbert.
Perhaps more immediately, the NIMH project could help researchers tune clinical trials of drugs to the right patients by focusing on discrete symptoms. For example, anhedonia, the inability to feel pleasure or seek pleasure, is a major symptom of depression, but it is also found in other patients, such as those with schizophrenia. By recruiting patients with measurable anhedonia, drug developers may be more likely to succeed in clinical trials than if they focused only on depression patients, says Cuthbert.
The NIMH project could also help to identify biomarkers of depression. “It could give us a structure to look at the pathology through different markers of the disease,” says Trivedi. “The goal is fantastic, but the proof is going to come in doing it.”](http://40.media.tumblr.com/2cee06d8ba637a69d1ed2f2d29d4c882/tumblr_mr0drrDP3b1rog5d1o1_500.jpg)
The Search for the Best Depression Treatment
Brain scans, blood samples, and other diagnostic tests could one day direct doctors to the best treatments for depression patients and uncover the biological basis of the condition.
When someone is diagnosed with depression, patient and doctor often begin a long trial-and-error process of testing different treatments. Sometimes they work, sometimes they don’t, so patients may try several options before finding the best one. But in the future, a brain scan, blood test, or some combination could help guide doctors to the best drugs, or lead them to suggest talk therapy.
Recently, Emory University researcher Helen Mayberg reported that a PET scan, a commonly used imaging method, can reveal whether a patient will respond better to an antidepressant or cognitive behavioral therapy. And in May, Medscape reported that David Mischoulon of Massachusetts General Hospital presented findings that the amount of a particular protein in the blood of depression patients could indicate whether a patient would do better by adding a form of folic acid to his or her treatment.
A key goal of such research is to distinguish between causes of depression. “The presence of certain biomarkers might give us a clue whether [a particular patient’s] depression is truly biologically driven, or whether it is depression like sadness over an event,” says Mischoulon. “If we can identify people who have these biological bases, it might suggest these patients might do better with medications, as opposed to psychotherapies or meditation.”
According to the World Health Organization, depression is the leading cause of disability globally. Many people do not seek or do not have access to treatment, and among those who do, fewer than 40 percent of depression patients improve with the first type of treatment they try. The problem is not that treatments like antidepressants and cognitive behavioral therapy don’t work, it’s that no one treatment works for every patient. Researchers from many disciplines, from neuroscience to genomics, are studying this complex disorder, which likely represents many different conditions with unique origins and treatments. Large clinical trials to predict a patient’s response to therapy or drugs based on brain or body biomarkers could improve treatment for future patients and perhaps uncover a clearer understanding of depression’s origins.
“You see now a number of big studies on predictive biomarkers,” says Mayberg, who has pioneered pacemaker-like implants as a treatment for severe cases of depression. She’s also involved in a large study of patients who will be treated with antidepressants or cognitive behavioral therapy based on brain scans. “It’s going to be interesting over the next year or two to see how this plays out,” she says. One question will be whether researchers will be able to identify markers that are both unambiguous but also practical to test. Brain scans may be the best place to start, she says, because they focus on the origin of the condition, but once good biomarkers are identified via brain scan, surrogates found in the blood may provide a simpler and more affordable option.
One challenge for researchers is that depression is probably a conglomeration of many diseases, says Madhukar Trivedi, a University of Texas Southwestern researcher heading a large trial that is trying to distinguish patients who respond better to one type of antidepressant compared to another. “There are a lot of subtypes in depression, so any given marker, whether genetic, protein, imaging, or EEG, ends up accounting for only a small percentage of variance for any group of patients,” says Trivedi.
If these researchers are successful, they could dramatically change how depression is treated and perhaps diagnosed. Doctors in the United States use the Diagnostic and Statistical Manual of Mental Disorders, or DSM, to diagnose depression. The diagnoses are largely based on the collection of symptoms presented or described by patients. In May, the head of the National Institute of Mental Health, Thomas Insel, announced that his institution would focus its research in areas other than the categories presented by the DSM. “Patients with mental disorders deserve better,” he said.
Bruce Cuthbert is heading the NIMH’s project to establish new ways of studying mental illness and potentially to improve future versions of the DSM by more precisely identifying the brain abnormalities in various diseases, including depression. The idea behind the project is to map out the genetic, circuit, and cognitive aspects of mental illness and to focus on individual features of disorders instead of clinical diagnoses. It could provide the information necessary to improve the DSM so that it is based on neuroscience and not just collections of symptoms. “In the future, we might define the disorders differently, or we might not. But this project will provide a framework to look at neural systems and how they operate and how that contributes to disease,” says Cuthbert.
Perhaps more immediately, the NIMH project could help researchers tune clinical trials of drugs to the right patients by focusing on discrete symptoms. For example, anhedonia, the inability to feel pleasure or seek pleasure, is a major symptom of depression, but it is also found in other patients, such as those with schizophrenia. By recruiting patients with measurable anhedonia, drug developers may be more likely to succeed in clinical trials than if they focused only on depression patients, says Cuthbert.
The NIMH project could also help to identify biomarkers of depression. “It could give us a structure to look at the pathology through different markers of the disease,” says Trivedi. “The goal is fantastic, but the proof is going to come in doing it.”
The Anorexic Brain
Neuroimaging improves understanding of eating disorder
In a spacious hotel room not far from the beach in La Jolla, Calif., Kelsey Heenan gripped her fiancé’s hand. Heenan, a 20-year-old anorexic woman, couldn’t believe what she was hearing. Walter Kaye, director of the eating disorders program at the University of California, San Diego, was telling a handful of rapt patients and their family members what the latest brain imaging research suggested about their disorder.
It’s not your fault, he told them.
Heenan had always assumed that she was to blame for her illness. Kaye’s data told a different story. He handed out a pile of black-and-white brain scans — some showed the brains of healthy people, others were from people with anorexia nervosa. The scans didn’t look the same. “People were shocked,” Heenan says. But above all, she remembers, the group seemed to sigh in relief, breathing out years of buried guilt about the disorder. “It’s something in the way I was wired — it’s something I didn’t choose to do,” Heenan says. “It was pretty freeing to know that there could be something else going on.”
Years of psychological and behavioral research have helped scientists better understand some signs and triggers of anorexia. But that knowledge hasn’t straightened out the disorder’s tangled roots, or pointed scientists to a therapy that works for everyone. “Anorexia has a high death rate, it’s expensive to treat and people are chronically ill,” says Kaye.
Kaye’s program uses a therapy called family-based treatment, or FBT, to teach adolescents and their families how to manage anorexia. A year after therapy, about half of the patients treated with FBT recover. In the world of eating disorders, that’s success: FBT is considered one of the very best treatments doctors have. To many scientists, that just highlights how much about anorexia remains unknown.
Kaye and others are looking to the brain for answers. Using brain imaging tools and other methods to explore what’s going on in patients’ minds, researchers have scraped together clues that suggest anorexics are wired differently than healthy people. The mental brakes people use to curb impulsive instincts, for example, might get jammed in people with anorexia. Some studies suggest that just a taste of sugar can send parts of the brain barrelling into overdrive. Other brain areas appear numb to tastes — and even sensations such as pain. For people with anorexia, a sharp pang of hunger might register instead as a dull thud.
The mishmash of different brain imaging data is just beginning to highlight the neural roots of anorexia, Kaye says. But because starvation physically changes the brain, researchers can run into trouble teasing out whether glitchy brain wiring causes anorexia, or vice versa. Still, Kaye thinks understanding what’s going on in the brain may spark new treatment ideas. It may also help the eating disorder shake off some of its noxious stereotypes.
“One of the biggest problems is that people do not take this disease seriously,” says James Lock, an eating disorders researcher at Stanford University who cowrote the book on family-based treatment. “No one gets upset at a child who has cancer,” he says. “If the treatment is hard, parents still do it because they know they need to do it to make their child well.”
Pop culture often paints anorexics as willful young women who go on diets to be beautiful, he says. But, “you can’t just choose to be anorexic,” Lock adds. “The brain data may help counteract some of the mythology.”
Beyond dieting
A society that glamorizes thinness can encourage unhealthy eating behaviors in kids, scientists have shown. A 2011 study of Minnesota high school students reported that more than half of girls had dieted within the past year. Just under a sixth had used diet pills, vomiting, laxatives or diuretics.
But a true eating disorder goes well beyond an unhealthy diet. Anorexia involves malnutrition, excessive weight loss and often faulty thinking about one of the body’s most basic drives: hunger. The disorder is also rare. Less than 1 percent of girls develop anorexia. The disease crops up in boys too, but adolescent girls — especially in wealthy countries such as the U.S., Australia and Japan — are most likely to suffer from the illness.
As the disease progresses, people with anorexia become intensely afraid of getting fat and stick to extreme diets or exercise schedules to drop pounds. They also misjudge their own weight. Beyond these diagnostic hallmarks, patients’ symptoms can vary. Some refuse to eat, others binge and purge. Some live for years with the illness, others yo-yo between weight gain and loss. Though most anorexics gain back some weight within five years of becoming ill, anorexia is the deadliest of all mental disorders.
Though anorexia tends to run in families, scientists haven’t yet hammered out the suite of genes at play. Some individuals are particularly vulnerable to developing an eating disorder. In these people, stressful life changes, such as heading off to college, can tip the mental scales toward anorexia.
For decades, scientists have known that anorexic children behave a little differently. In school and sports, anorexic kids strive for perfection. Though Heenan, a former college basketball player, didn’t notice her symptoms creeping in until the end of high school, she remembers initiating strict practice regimens as a child. Starting in second grade, Heenan spent hours perfecting her jump shot, shooting the ball again and again until she had the technique exactly right — until her form was flawless.
“It’s very rare for me to see a person with anorexia in my office who isn’t a straight-A student,” Lock says. Even at an early age, people who later develop the eating disorder tend to exert an almost superhuman ability to practice, focus or study. “They will work and work and work,” says Lock. “The problem is they don’t know when to stop.”
In fact, many scientists think anorexics’ brains might be wired for willpower, for good and ill. Using new imaging tools that let scientists watch as a person’s mental gears grind through different tasks, researchers are starting to pin down how anorexic brains work overtime.
Different wiring: Studies of the brains of people with anorexia have revealed a number of complex brain circuits that show changes in activity compared with healthy people. Medical RF, adapted by M. Atarod
Control signs
To glimpse the circuits that govern self-control, experimental neuropsychologist Samantha Brooks uses functional magnetic resonance imaging, or fMRI, a tool that measures and maps brain activity. Last year, she and colleagues scanned volunteers as they imagined eating high-calorie foods, such as chocolate cake and French fries, or using inedible objects such as clothespins piled on a plate. One result gave Brooks a jolt. A center of self-control in anorexics’ brains sprung to life when the volunteers thought about food — but only in the women who severely restricted their calories, her team reported March 2012 in PLOS ONE.
The control center, two golf ball–sized chunks of tissue called the dorsolateral prefrontal cortex, or DLPFC, helps stamp out primitive urges. “They put a brake on your impulsive behaviors,” says Brooks, now at the University of Cape Town in South Africa.
For Brooks, discovering the DLPFC data was like finding a tiny vein of gold in a heap of granite. The control center could be the nugget that reveals how anorexics clamp down on their appetites. So she and her colleagues devised an experiment to test anorexics’ DLPFC. Using a memory task known to engage the brain region, the researchers quizzed volunteers while showing them subliminal images. The quizzes tested working memory, the mental tool that lets people hold phone numbers in their heads while hunting for a pen and paper. Compared with healthy people, anorexics tended to get more answers right, Brooks’ team wrote June 2012 in Consciousness and Cognition. “The patients were really good,” Brooks says. “They hardly made any mistakes.”
A turbocharged working memory could help anorexics hold on to rules they set for themselves about food. “It’s like saying ‘I will only eat a salad at noon, I will only eat a salad at noon,’ over and over in your mind,” says Brooks. These mantras may become so ingrained that an anorexic person can’t escape them.
But looking at subliminal images of food distracted anorexics from the memory task. “Then they did just as well as the healthy people,” Brooks says. The results suggest that anorexic people might tap into their DLPFC control circuits when faced with food.
James Lock has also seen signs of self-control circuits gone awry in people with eating disorders. In 2011, he and colleagues scanned the brains of teenagers with different eating disorders while signaling them to push a button. While volunteers lay inside the fMRI machine, researchers flashed pictures of different letters on an interior screen. For every letter but “X,” Lock’s group told the teens to push a button. During the task, anorexic teens who obsessively cut calories tended to have more active visual circuits than healthy teens or those with bulimia, a disorder that compels people to binge and purge. The result isn’t easy to explain, says Lock. “Anorexics may just be more focused in on the task.”
Bulimics’ brains told a simpler story. When teens with bulimia saw the letter “X,” broad swaths of their brains danced with activity — more so than the healthy or calorie-cutting anorexic volunteers, Lock’s team reported in the American Journal of Psychiatry. For bulimics, controlling the impulse to push the button may take more brain power than for others, Lock says.
Though the data don’t reveal differences in self-control between anorexics and healthy people, Lock thinks that anorexics’ well-documented ability to swat away urges probably does have signatures in the brain. He notes that his study was small, and that the “healthy” people he used as a control group might have shared similarities with anorexics. “The people who tend to volunteer are generally pretty high performers,” he says. “The chances are good that my controls are a little bit more like anorexics than bulimics.”
Still, Lock’s results offered another flicker of proof that people with eating disorders might have glitches in their self-control circuits. A tight rein on urges could help steer anorexics toward illness, but the parts of their brain tuned into rewards, such as sugary snacks, may also be a little off track.
Sugar low
When an anorexic woman unexpectedly gets a taste of sugar (yellow) or misses out on it (blue), her brain’s reward circuitry shows more activity than a healthy-weight or obese woman’s. Anorexics’ reward-processing systems may be out of order. Credit: G. Frank et al/ Neuropsychopharmacology 2012
For many anorexics, food just doesn’t taste very good. A classic symptom of the disorder is anhedonia, or trouble experiencing pleasure. Parts of Heenan’s past reflect the symptom. When she was ill, she had trouble remembering favorite dishes from childhood, for example — a blank spot common to anorexics. “I think I enjoyed some things,” she says. Beyond frozen yogurt, she can’t really rattle off a list.
After Heenan started seriously restricting her calories in college, only one aspect of food made her feel satisfied. Skipping, rather than eating, meals felt good, she says. Some of Heenan’s symptoms may have stemmed from frays in her reward wiring, the brain circuitry connecting food to pleasure. In the past few years, researchers have found that the chemicals coursing through healthy people’s reward circuits aren’t quite the same in anorexics. And studies in rodents have linked chemical changes in reward circuitry to under- and overeating.
To find out whether under- and overweight people had altered brain chemistry, eating disorder researcher Guido Frank of the University of Colorado Denver studied anorexic, healthy-weight and obese women. He and his colleagues trained volunteers to link images, such as orange or purple shapes, with the taste of a sweet solution, slightly salty water or no liquid. Then, the researchers scanned the women’s brains while showing them the shapes and dispensing tiny squirts of flavors. But the team threw in a twist: Sometimes the flavors didn’t match up with the right images.
When anorexics got an unexpected hit of sugar, a surge of activity bloomed in their brains. Obese people had the opposite response: Their brains didn’t register the surprise. Healthy-weight women fit somewhere in the middle, Frank’s team reported August 2012, in Neuropsychopharmacology. While obese people might not be sensitive to sweets anymore, a little sugar rush goes a long way for anorexics. “It’s just too much stimulation for them,” Frank says.
One of the lively regions in anorexics’ brains was the ventral striatum, a lump of nerve cells that’s part of a person’s reward circuitry. The lump picks up signals from dopamine, a chemical that rushes in when most people see a sugary treat.
Frank says that it’s possible cutting calories could sculpt a person’s brain chemistry, but he thinks some young people are just more likely to become sugar-sensitive than others. Frank suspects anorexics’ dopamine-sensing equipment might be out of alignment to begin with. And he may be onto something. Recently, researchers in Kaye’s lab at UCSD showed that the same chemical that makes people perk up when a coworker brings in a box of doughnuts might actually trigger anxiety in anorexics.
Mixed signals
Usually a rush of dopamine triggers euphoria or a boost of energy, says Ursula Bailer, a psychiatrist and neuroimaging researcher at UCSD. Anorexics don’t seem to pick up those good feelings.
When Bailer and colleagues gave volunteers amphetamine, a drug known to trigger dopamine release, and then asked them to rate their feelings, healthy people stuck to a familiar script. The drug made them feel intensely happy, Bailer’s team described March 2012 in the International Journal of Eating Disorders. Researchers linked the volunteers’ happy feelings to a wave of dopamine flooding the brain, using an imaging technique to track the chemical’s levels.
But anorexics said something different. “People with anorexia didn’t feel euphoria — they got anxious,” Bailer says. And the more dopamine coursing through anorexics’ brains, the more anxious they felt. Anorexics’ reaction to the chemical could help explain why they steer clear of food — or at least foods that healthy people find tempting. “Anorexics don’t usually get anxious if you give them a plate of cucumbers,” Bailer says.
Beyond the anxiety finding, one other aspect of the study sticks out: Instead of examining sick patients, Bailer, Kaye and colleagues recruited women who had recovered from anorexia. By studying people whose brains are no longer starving, Kaye’s team hopes to sidestep the chicken-and-egg question of whether specific brain signatures predispose people to anorexia or whether anorexia carves those signatures in the brain.
Though Kaye says that there’s still a lot scientists don’t know about anorexia, he’s convinced it’s a disorder that starts in the brain. Compared with healthy children, anorexic children’s brains are getting different signals, he says. “Parents have to realize that it’s very hard for these kids to change.”
Kaye thinks imaging data can help families reframe their beliefs about anorexia, which might help them handle tough treatments. He thinks the data can also offer new insights into therapies tailored for anorexics’ specific traits.
Sensory underload
One trait Kaye has focused on is anorexics’ sense of awareness of their bodies. Peel back the outer lobes of the brain by the temples, and the bit that handles body awareness pops into view. These regions, little islands of tissue called the insula, are one of the first brain areas to register pain, taste and other sensations. When people hold their breath, for example, and feel the panicky claws of air hunger, “the insula lights up like crazy,” Kaye says.
Kaye and colleagues have shown that the insulas of people with anorexia seem to be somewhat dulled to sensations. In a recent study, his team strapped heat-delivering gadgets to volunteers’ arms and cranked the devices to painfully hot temperatures while measuring insula activity via fMRI.
Compared with healthy volunteers, bits of recovered anorexics’ insulas dimmed when the researchers turned up the heat. But when researchers simply warned that pain was coming, other parts of the brain region flared brightly, Kaye’s team reported in January in the International Journal of Eating Disorders. For people who have had anorexia, actually feeling pain didn’t seem as bad as anticipating it. “They don’t seem to be sensing things correctly,” says Kaye.
If anorexics can’t detect sensations like pain properly, they may also have trouble picking up other signals from the body, such as hunger. Typically when people get hungry, their insulas rev up to let them know. And in healthy hungry people, a taste of sugar really gets the insula excited. For anorexics, this hunger-sensing part of the brain seems numb. Parts of the insula barely perked up when recovered anorexic volunteers tasted sugar, Kaye’s team showed this June in the American Journal of Psychiatry. The findings “may help us understand why people can starve themselves and not get hungry,” Kaye says.
Though the brain region that tells people they’re hungry might have trouble detecting sweet signals, some reward circuits seem to overreact to the same cues. Combined with a tendency to swap happiness for anxiety, and a mental vise grip on behavior, anorexics might have just enough snags in their brain wiring to tip them toward disease.
Now, Kaye’s group hopes to tap neuroimaging data for new treatment ideas. One day, he thinks doctors might be able to help anorexics “train” their insulas using biofeedback. With real-time brain scanning, patients could watch as their insulas struggle to pick up sugar signals, and then practice strengthening the response. More effective treatment options could potentially spare anorexics the relapses many patients suffer.
Heenan says she’s one of the lucky ones. Four years have passed since she first saw the anorexic brain images at UCSD. In the months following her treatment, Heenan and her family worked together to rebuild her relationship with food. At first, her fiancé picked out all her meals, but step by step, Heenan earned autonomy over her diet. Today, Heenan, a coordinator for Minneapolis’ public schools, is married and has a new puppy. “Life can be good,” she says. “Life can be fun. I want other people to know the freedom that I do.”
Searching for treatments
The bowl of pasta sitting in front of Kelsey Heenan didn’t look especially scary.
Spaghetti, chopped asparagus and chunks of chicken glistened in an olive oil sauce. Usually, such savory fare might make a person’s mouth water. But when Heenan’s fiancé served her a portion, she started sobbing. “You can’t do this to me,” she told him. “I thought you loved me!”
Heenan was confronting her “fear foods” at the Eating Disorders Center for Treatment and Research at UCSD. Therapists in her treatment program, Intensive Multi-Family Therapy, spend five days teaching anorexic patients and families about the disorder and how to encourage healthy eating. “There’s no blame,” says Christina Wierenga, a clinical neuropsychologist at UCSD. “The focus is just on having the parent refeed the child.” Therapists lay out healthy meals and portion sizes for teens, bolster parents’ self-confidence and hammer home the dangers of not eating. Heenan compares the experience to boot camp. But by the end of her time at the center, she says, “I was starting to see glimpses of what life could be like as a healthy person.”
Treatment options for anorexia include a broad mix of behavioral and medication-based therapies. Most don’t work very well, and many lack the support of evidence-based trials. Hospitalizing patients can boost short-term weight gain, “but when people go home they lose all the weight again,” says Stanford University’s James Lock, one of the architects of family-based treatment. That treatment is currently considered the most effective therapy for adolescent anorexics.
In a 2010 clinical trial, half of teens who underwent FBT maintained a normal weight a year after therapy. In contrast, only a fifth of teens treated with adolescent-focused individual therapy, which aims to help kids cope with emotions without using starvation, hit the healthy weight goal.
Few good options exist for adult anorexics, a group notorious for dropping out of therapy. New work hints that cognitive remediation therapy, or CRT, which uses cognitive exercises to change anorexics’ behaviors, has potential. After two months of CRT, only 13 percent of patients abandoned treatment, and most regained some weight, Lock and colleagues reported in the April International Journal of Eating Disorders. Researchers still need to find out, however, if CRT helps patients keep weight on long-term.
(Source: sciencenews.org)