Migraine and Depression Together May Be Linked with Brain Size

Older people with a history of migraines and depression may have smaller brain tissue volumes than people with only one or neither of the conditions, according to a new study in the May 22, 2013, online issue of Neurology®, the medical journal of the American Academy of Neurology.

“Studies show that people with migraine have double the risk of depression compared to people without migraine,” said study author Larus S. Gudmundsson, PhD, with the National Institute on Aging and the Uniformed Services University of the Health Sciences, in Bethesda, Md. Gudmundsson is also a member of the American Academy of Neurology. “We wanted to find out whether having both conditions together possibly affected brain size.”

For the study, 4,296 people with an average age of 51 were tested for migraine headache from 1967 to 1991; they were later assessed from 2002 to 2006 at an average age of 76 for a history of major depressive disorder (depression). Participants also underwent MRI, from which brain tissue volumes were estimated. A total of 37 participants had a history of both migraine and depression, while 2,753 had neither condition.

The study found that people with both migraine and depression had total brain tissue volumes an average of 19.2 milliliters smaller than those without either condition. There was no difference in the total brain volume when comparing people with only one of the conditions to people with neither condition.

“It is important to note that participants in this study were imaged using MRI once, so we cannot say that migraine and depression resulted in brain atrophy. In future studies, we need to examine at what age participants develop both migraine and depression and measure their brain volume changes over time in order to determine what comes first,” said Gudmundsson.

Gudmundsson noted that some of the factors leading to a joint effect of migraine and depression on brain volume may include pain, brain inflammation, genetics and differences in a combination of social and economic factors. “Our study suggests that people with both migraine and depression may represent a unique group from those with only one of these conditions and may also require different strategies for long-term treatment.”

‘Revealing the scientific secrets of why people can’t stop after eating one potato chip

The scientific secrets underpinning that awful reality about potato chips — eat one and you’re apt to scarf ’em all down — began coming out of the bag today in research presented at the 245^th National Meeting & Exposition of the American Chemical Society, the world’s largest scientific society. The meeting, which news media have termed “The World Series of Science,” features almost 12,000 presentations on new discoveries and other topics. It continues here through today.

Tobias Hoch, Ph.D., who conducted the study, said the results shed light on the causes of a condition called “hedonic hyperphagia” that plagues hundreds of millions of people around the world.

“That’s the scientific term for ‘eating to excess for pleasure, rather than hunger,’” Hoch said. “It’s recreational over-eating that may occur in almost everyone at some time in life. And the chronic form is a key factor in the epidemic of overweight and obesity that here in the United States threatens health problems for two out of every three people.”

The team at FAU Erlangen-Nuremberg, in Erlangen, Germany, probed the condition with an ingenious study in which scientists allowed one group of laboratory rats to feast on potato chips. Another group got bland old rat chow. Scientists then used high-tech magnetic resonance imaging (MRI) devices to peer into the rats’ brains, seeking differences in activity between the rats-on-chips and the rats-on-chow.

With recent studies showing that two-thirds of Americans are obese or overweight, this kind of recreational over-eating continues to be a major problem, health care officials say.

Among the reasons why people are attracted to these foods, even on a full stomach, was suspected to be the high ratio of fats and carbohydrates, which send a pleasing message to the brain, according to the team. In the study, while rats also were fed the same mixture of fat and carbohydrates found in the chips, the animals’ brains reacted much more positively to the chips.

“The effect of potato chips on brain activity, as well as feeding behavior, can only partially be explained by its fat and carbohydrate content,” explained Tobias Hoch, Ph.D. “There must be something else in the chips that make them so desirable,” he said.

In the study, rats were offered one out of three test foods in addition to their standard chow pellets: powdered standard animal chow, a mixture of fat and carbs, or potato chips. They ate similar amounts of the chow as well as the chips and the mixture, but the rats more actively pursued the potato chips, which can be explained only partly by the high energy content of this snack, he said. And, in fact, they were most active in general after eating the snack food.

Although carbohydrates and fats also were a source of high energy, the rats pursued the chips most actively and the standard chow least actively. This was further evidence that some ingredient in the chips was sparking more interest in the rats than the carbs and fats mixture, Hoch said.

Hoch explained that the team mapped the rats’ brains using Manganese-Enhanced Magnetic Resonance Imaging (MEMRI) to monitor brain activity. They found that the reward and addiction centers in the brain recorded the most activity. But the food intake, sleep, activity and motion areas also were stimulated significantly differently by eating the potato chips.

“By contrast, significant differences in the brain activity comparing the standard chow and the fat carbohydrate group only appeared to a minor degree and matched only partly with the significant differences in the brain activities of the standard chow and potato chips group,” he added.

Since chips and other foods affect the reward center in the brain, an explanation of why some people do not like snacks is that “possibly, the extent to which the brain reward system is activated in different individuals can vary depending on individual taste preferences,” according to Hoch. “In some cases maybe the reward signal from the food is not strong enough to overrule the individual taste.” And some people may simply have more willpower than others in choosing not to eat large quantities of snacks, he suggested.

If scientists can pinpoint the molecular triggers in snacks that stimulate the reward center in the brain, it may be possible to develop drugs or nutrients to add to foods that will help block this attraction to snacks and sweets, he said. The next project for the team, he added, is to identify these triggers. He added that MRI studies with humans are on the research agenda for the group.

On the other hand, Hoch said there is no evidence at this time that there might be a way to add ingredients to healthful, albeit rather unpopular, foods like Brussels sprouts to affect the rewards center in the brain positively.

New minimally invasive, MRI-guided laser treatment for brain tumor found to be promising in study

The first-in-human study of the NeuroBlate™ Thermal Therapy System finds that it appears to provide a new, safe and minimally invasive procedure for treating recurrent glioblastoma (GBM), a malignant type of brain tumor. The study, which appears April 5 in the Journal of Neurosurgery online, was written by lead author Andrew Sloan, MD, Director of Brain Tumor and Neuro-Oncology Center at University Hospitals (UH) Case Medical Center and Case Comprehensive Cancer Center, who also served as co-Principal Investigator, as well as Principal Investigator Gene Barnett, MD, Director of the Brain Tumor and Neuro-Oncology Center at Cleveland Clinic and Case Comprehensive Cancer Center, and colleagues from UH, Cleveland Clinic, Cleveland Clinic Florida, University of Manitoba and Case Western Reserve University.

NeuroBlate™ is a device that “cooks” brain tumors in a controlled fashion to destroy them. It uses a minimally invasive, MRI-guided laser system to coagulate, or heat and kill, brain tumors. The procedure is conducted in an MRI machine, enabling surgeons to plan, steer and see in real-time the device, the heat map of the area treated by the laser and the tumor tissue that has been coagulated.

"This technology is unique in that it allows the surgeon not only to precisely control where the treatment is delivered, but the ability to visualize the actual effect on the tissue as it is happening," said Dr. Sloan. "This enables the surgeon to adjust the treatment continuously as it is delivered, which increases precision in treating the cancer and avoiding surrounding healthy brain tissue."

The study was a Phase I clinical trial investigating the safety and performance of NeuroBlate™ (formerly known as AutoLITT™), a specially-designed laser probe system. The FDA gave the system’s developer Monteris Medical and the Case Comprehensive Cancer Center, (comprised of the UH Case Medical Center, Cleveland Clinic, and Case Western Reserve University School of Medicine), an investigatory device exemption (IDE) to study the system in patients with GBMs. The device has recently been cleared by the FDA due, in part, to the results of the study.

The paper describes the treatment of the first 10 patients with this technology. These patients, who had a median age of 55, had tumors which were diagnosed to be inoperable or “high risk” for open surgical resection because of their location close to vital areas in the brain, or difficult to access with conventional surgery.

"Overall the NeuroBlate™ procedure was well-tolerated," said Dr. Sloan. "All 10 patients were alert and responsive within one to two hours post-operatively and nine out of the 10 patients were ambulatory within hours. Response and survival was also nearly 10 ½ months, better than expected for patients with such advanced disease."

"Previous attempts using less invasive approaches such as brachytherapy and stereotactic radiosurgery have proven ineffective in recent meta-analysis and randomized trials," said Dr. Barnett. "However, unlike therapies using ionizing radiation, NeuroBlate™ therapy results in tumor death at the time of the procedure. A larger national study will be developed, as a result of this initial success."

Path Found to a Combined MRI and CT Scanner

A technology that better targets an X-ray imager’s field of view could allow various medical imaging technologies to be integrated into one. This could produce sharper, real-time pictures from inside the human body, says a researcher who hopes to one day build such a unified imager.


Ge Wang, the director of Rensselaer Polytechnic Institute’s Biomedical Imaging Center, in Troy, N.Y., calls his vision omni-tomography. Mixing and matching imaging techniques, such as computed tomography, magnetic resonance imaging, and single-photon emission computed tomography, could improve biomedical research and facilitate personalized medicine, says Wang, an IEEE Fellow.


To fit these imaging methods together, Wang and his collaborators have been developing a technology called interior tomography. In standard CT, X‑rays pass through two-dimensional slices of the body, and then a computer processes the data to build up a picture. If the scanner is trying to image the aorta, for instance, it will X-ray a whole section of the chest, including the points where the body ends and the open air begins. That boundary provides the image-building algorithm with defined edges and the background information it needs to operate. But interior tomography focuses only on structures inside the body, which reduces the patient’s radiation exposure. “If you’re only interested in the heart, why bother to cover your whole chest with X-rays?” says Wang.

Narrowing the view, however, eliminates the usual reference points needed to create an image conventionally. Interior tomography relies on a different set of hints. The new technique uses information about how substances within the body (such as blood) and air pockets alter X-rays to provide the algorithm with a base for reconstructing the image. It can even use old X-ray images of the same patient to help out.

Focusing on a specific region has advantages, particularly with patients too big for conventional scanners. “If an object is wider than the X-ray beam width, classic theory says you cannot do an accurate reconstruction,” says Wang. That’s not a concern with interior tomography, he says.

What’s more, Wang’s team has shown that this concept can be generalized for use in imaging methods other than CT scanning, including MRI. And that could lead to a true fusion of major medical imaging techniques. In part that’s because the technique allows the use of smaller X-ray detectors, which in turn makes it possible to fit more scanners into the same machine. 


There are already systems that combine two imaging methods—PET and CT or SPECT and CT, for instance. But those systems usually apply different methods in sequence rather than simultaneously, making it harder to see biological processes in action. The combination of CT and MRI has never been attempted before, but Wang says it’s possible now.


In fact, he and his collaborators in Australia, China, and the United States recently came up with a top-level engineering design for a CT-MRI scanner. They hope to present their design in June at the International Meeting on Fully Three-Dimensional Image Reconstruction in Radiology and Nuclear Medicine, in California. Applying interior tomography to MRI imaging allows the use of a weaker magnetic field, which is one way the design compensates for the incompatibility between powerful magnets in the MRI and rotating metal parts in the CT scanner. 


Wang’s team does not yet have the funding to build a combination CT-MRI scanner, but putting the two technologies together could prove useful. MRI gives high contrast and allows doctors to measure functional and even molecular changes; CT provides greater structural detail. Together, they might allow doctors to get a superior picture of processes in action, such as changes during a heart attack, or serve as a guide to a surgical procedure. The technology would be ideal for imaging vulnerable plaques, suggests Michael Vannier, one of Wang’s collaborators and a radiology professor at the University of Chicago. Vulnerable plaques are buildups on artery walls that are particularly unstable and prone to causing heart attack or stroke. A combination of structural, functional, and molecular information is needed to tell just how dangerous the plaque may be. “In the long run, we think putting many imaging modes together will give you more information,” Wang says.


Interior tomography “is certainly an interesting concept that takes the interest in combining modalities to the ‘ultimate’ level of a single device,” says Simon Cherry, director of the Center for Molecular and Genomic Imaging at the University of California, Davis. While omni-tomography is technically feasible, Cherry wonders whether it will make sense from a clinical and economic perspective. “There are some that say too many of our health-care dollars are spent on imaging, especially in the pursuit of defensive medicine. This will be an expensive machine,” he says. “These are the issues that may well determine whether this approach is successful.” 


Pig brain models provide insights into human cognitive development

A mutual curiosity about patterns of growth and development in pig brains has brought two University of Illinois research groups together. Animal scientists Rod Johnson and Ryan Dilger have developed a model of the pig brain that they plan to use to answer important questions about human brain development.

“It is important to characterize the normal brain growth trajectory from the neonatal period to sexual maturity,” said Johnson.

“Until we know how the brain grows, we don’t know what is going to change,” added Dilger.

In cooperation with the Beckman Institute, they performed MRI scans on the brains of 16 piglets, starting at the age of 2 weeks, then at 4 weeks, and then at 4-week intervals up to 24 weeks.

“We have world-class people at the Beckman Institute who are pushing and developing the next generation of neuroimaging technology, so we’re able to connect with them and take advantage of their expertise,” said Johnson.

Matt Conrad, a student in Johnson’s lab, used three-dimensional visualization software on over 200 images to manually segment each region on three planes. The software put the information together into a three-dimensional image of the pig brain. This is used to determine the volume of the different structures.

When the piglets were at Beckman for their imaging sessions, Dilger performed other tests, including diffusion tensor imaging (DTI), which shows how neural tracks develop, allowing the exploration of brain complexity and of how neurons form. It was also possible to measure neurochemicals, including creatine and acetylcholine, in the brain, which provides a unique insight into brain metabolism.

The end result of this work is what they call the deformable pig brain atlas.

“We are taking 16 pigs and averaging them, so it’s more representative of all pigs,” said Dilger. “You can then apply it to any individual pig to see how it’s different.”

“It’s called a deformable brain atlas because the software takes information from an individual and deforms it until it fits the template, and then you know how much it had to be deformed to fit,” Johnson explained. “So from that, you can tell whether a brain region is larger or smaller compared to the average.”

Johnson and Dilger said that the goal is to develop a tool for pigs that is equivalent to what is available for the mouse brain and make it publicly available. But they don’t want to stop with tool development.

“We want to use this to address important questions,” Johnson said.

One research direction being pursued in Johnson’s lab is to induce viral pneumonia in piglets at the point in the post-natal period when the brain is undergoing massive growth to see how it alters brain growth and development. They are also looking at effects of prenatal infections in the mother to see if that alters the trajectory of normal brain growth in the offspring. The risk for behavioral disorders and reduced stress resilience is increased by pre- and post-natal infection, but the developmental origins are poorly understood.

Dilger’s group is interested in the effects of early-life nutrition on the brain. They are looking at the effects of specific fatty acids as primary structural components of the human brain and cerebral cortex, and at choline, a nutrient that is important for DNA production and normal functioning of neurons.

“Choline deficiency has been tied to cognitive deficits in the mouse and human, and we’re developing a pig model to study the direct effects choline deficiency has on brain structure and function,” Dilger said. “Many women of child-bearing age may not be receiving enough choline in their diets, and recent evidence suggests this may ultimately affect learning and memory ability in their children. Luckily, choline can be found in common foods, especially eggs and meat products, including bacon.”

New MRI method fingerprints tissues and diseases

A new method of magnetic resonance imaging (MRI) could routinely spot specific cancers, multiple sclerosis, heart disease and other maladies early, when they’re most treatable, researchers at Case Western Reserve University and University Hospitals (UH) Case Medical Center suggest in the journal Nature.

Each body tissue and disease has a unique fingerprint that can be used to quickly diagnose problems, the scientists say.

By using new MRI technologies to scan for different physical properties simultaneously, the team differentiated white matter from gray matter from cerebrospinal fluid in the brain in about 12 seconds, with the promise of doing this much faster in the near future.

The technology has the potential to make an MRI scan standard procedure in annual check-ups, the authors believe. A full-body scan lasting just minutes would provide far more information and require no radiologist to interpret the data, making diagnostics cheap, compared to today’s scans, they contend.

"The overall goal is to specifically identify individual tissues and diseases, to hopefully see things and quantify things before they become a problem," said Mark Griswold, a radiology professor at Case Western Reserve School of Medicine and UH Case Medical Center. "But to try to get there, we’ve had to give up everything we knew about the MRI and start over."

Griswold has been working on this goal with Case Western Reserve’s Vikas Gulani, MD, an assistant professor of radiology, and Nicole Seiberlich, assistant professor of biomedical engineering, for a decade. During the last three years, they developed the technology and proved the concept with graduate student Dan Ma; Kecheng Liu, PhD, collaborations manager from Siemens Medical Solutions Inc.; Jeffrey L. Sunshine, MD, professor of radiology and a radiologist at UH Case Medical Center; and Jeffrey L. Duerk, dean of Case School of Engineering and professor of biomedical engineering.

(Image: Rex Features)

Scientists Find Way to Image Brain Waste Removal Process Which May Lead to Alzheimer’s Diagnostic

A novel way to image the entire brain’s glymphatic pathway, a dynamic process that clears waste and solutes from the brain that otherwise might build-up and contribute to the development of Alzheimer’s disease, may provide the basis for a new strategy to evaluate disease susceptibility, according to a research paper published online in The Journal of Clinical Investigation. Through contrast enhanced magnetic resonance imaging (MRI) and other tools, a Stony Brook University-led research team successfully mapped this brain-wide pathway and identified key anatomical clearance routes of brain waste.

In their article titled “Brain-wide pathway for waste clearance captured by contrast enhanced MRI,” Principal Investigator Helene Benveniste, MD, PhD, a Professor in the Departments of Anesthesiology and Radiology at Stony Brook University School of Medicine, and colleagues built upon a previous finding by Jeffrey Iliff, PhD, and Maiken Nedergaard, MD, PhD, from University of Rochester that initially discovered and defined the glymphatic pathway, where cerebral spinal fluid (CSF) filters through the brain and exchanges with interstitial fluid (ISF) to clear waste, similar to the way lymphatic vessels clear waste from other organs of the body. Despite the discovery of the glymphatic pathway, researchers could not visualize the brain wide flow of this pathway with previous imaging techniques.

“Our experiments showed proof of concept that the glymphatic pathway function can be measured using a simple and clinically relevant imaging technique,” said Dr. Benveniste. “This technique provides a three-dimensional view of the glymphatic pathway that captures movement of waste and solutes in real time. This will help us to define the role of the pathway in clearing matter such as amyloid beta and tau proteins, which affect brain processes if they build up.”

Dr. Benveniste said that the pathology of certain neurological conditions is associated with the accumulation of these proteins and other large extracellular aggregates. In particular, she explained that plaque deposits of these proteins are implicated in the development of Alzheimer’s disease, as well as chronic traumatic encephalopathy that occurs after repetitive mild traumatic brain injuries.