Before the cardiologist goes nuclear w/ stress #AHA17

Measuring troponin in CAD patients before embarking on stress testing may provide Read more

Virus hunting season open

Previously unknown viruses, identified by Winship + UCSF scientists, come from a patient with a melanoma that had metastasized to the Read more

#AHA17 highlight: cardiac pacemaker cells

Highlighting new research on engineering induced pacemaker cells from Hee Cheol Cho's Read more

brain imaging

Imaging sleep drunkenness: #IHAW2017

At some point, everyone has experienced a temporary groggy feeling after waking up called sleep inertia. Scientists know a lot about sleep inertia already, including how it impairs cognitive and motor abilities, and how it varies with the time of day and type of sleep that precedes it. They even have pictures of how the brain wakes up piece by piece.

People with idiopathic hypersomnia or IH display something that seems stronger, termed “sleep drunkenness,” which can last for hours. Czech neurologist Bedrich Roth, the first to identify IH as something separate from other sleep disorders, proposed sleep drunkenness as IH’s defining characteristic.

Note: Emory readers may recall the young Atlanta lawyer treated for IH by David Rye, Kathy Parker and colleagues several years ago. Our post today is part of IH Awareness Week® 2017.

Sleep drunkenness is what makes IH distinctive in comparison to narcolepsy, especially narcolepsy with cataplexy, whose sufferers tend to fall asleep quickly. Those with full body cataplexy can collapse on the floor in response to emotions such as surprise or amusement. In contrast, people with IH tend not to doze off so suddenly, but they do identify with the statement “Waking up is the hardest thing I do all day.”

At Emory, neurologist Lynn Marie Trotti and colleagues are in the middle of a brain imaging study looking at sleep drunkenness.

“We want to find out if sleep drunkenness in IH is the same as what happens to healthy people with sleep inertia and is more pronounced, or whether it’s something different,” Trotti says. Read more

Posted on by Quinn Eastman in Neuro Leave a comment

Sidestepping the placebo effect when studying depression

Research on depression must deal with a major obstacle: the placebo effect. This is the observation that patients improve in response to the sugar pills given as controls in clinical studies.

Clinical trial designers can incorporate various clever strategies to minimize the placebo effect, which is actually comprised of several statistical and psychological factors. Investigators can try to enhance, dissect or even “harness” them. [A recent piece in the New York Times from Jo Marchant focuses on the placebo effect in studies of pain relief.]

Emory psychiatrist Andrew Miller and his team have been developing a different approach over the last few years: studying symptoms of depression in people who are being treated for something else. This allows them to sidestep, at least partially, the cultural construct of depression, from William Styron to Peter Kramer to direct-to-consumer television ads.

Interferon alpha, a treatment used against hepatitis C virus infection and some forms of cancer, is a protein produced by the immune system that spurs inflammation. It also can induce symptoms of depression, such as fatigue and malaise. There are some slight differences with psychiatric depression, which Miller’s team describes here (less guilt!), but they conclude that there is a “high degree of overlap.”

Miller and his colleagues, including Jennifer Felger and Ebrahim Haroon, have documented how interferon-alpha-induced inflammation affects the brains of hepatitis C and cancer patients in several papers. That research, in turn, informs their more recent fruitful investigations of inflammation in the context of major depression. More on that soon.

Posted on by Quinn Eastman in Immunology, Neuro Leave a comment

Inflammation linked to weakened reward circuits in depression

About one third of people with depression have high levels of inflammation markers in their blood. New research indicates that persistent inflammation affects the brain in ways that are connected with stubborn symptoms of depression, such as anhedonia, the inability to experience pleasure.

The results were published online on Nov. 10 in Molecular Psychiatry.

The findings bolster the case that the high-inflammation form of depression is distinct, and are guiding researchers’ plans to test treatments tailored for it.

Anhedonia is a core symptom of depression that is particularly difficult to treat, says lead author Jennifer Felger, PhD, assistant professor of psychiatry and behavioral sciences at Emory University School of Medicine and Winship Cancer Institute.

“Some patients taking antidepressants continue to suffer from anhedonia,” Felger says. “Our data suggest that by blocking inflammation or its effects on the brain, we may be able to reverse anhedonia and help depressed individuals who fail to respond to antidepressants.”

In a study of 48 patients with depression, high levels of the inflammatory marker CRP (C-reactive protein) were linked with a “failure to communicate”, seen through brain imaging, between regions of the brain important for motivation and reward.

Emory researchers have found that high inflammation in depression is linked to a "failure to communicate" between two parts of the brain: the ventral striatum (VS, vertical cross section) and the ventromedial prefrontal cortex (vmPFC, horizontal).

Emory researchers have found that high inflammation in depression is linked to a “failure to communicate” between two parts of the brain: the ventral striatum (VS, vertical cross section) and the ventromedial prefrontal cortex (vmPFC, horizontal). Images from Felger et al, Molecular Psychiatry (2015).

Neuroscientists can infer that two regions of the brain talk to each other by watching whether they light up in magnetic resonance imaging at the same times or in the same patterns, even when someone is not doing anything in particular. They describe this as “functional connectivity.”

More here.

Posted on by Quinn Eastman in Neuro Leave a comment

Redrawing the brain’s motor map

Neuroscientists at Emory have refined a map showing which parts of the brain are activated during head rotation, resolving a decades-old puzzle. Their findings may help in the study of movement disorders affecting the head and neck, such as cervical dystonia and head tremor.

The results were published in Journal of Neuroscience.

In landmark experiments published in the 1940s and 50s, Canadian neurosurgeon Wilder Penfield and colleagues determined which parts of the motor cortex controlled the movements of which parts of the body.

Penfield stimulated the brain with electricity in patients undergoing epilepsy surgery, and used the results to draw a “motor homunculus”: a distorted representation of the human body within the brain. Penfield assigned control of the neck muscles to a region between those that control the fingers and face, a finding inconsistent with some studies that came later.

Using modern functional MRI (magnetic resonance imaging), researchers at Emory University School of Medicine have shown that the neck’s motor control region in the brain is actually between the shoulders and trunk, a location that more closely matches the arrangement of the body itself.

“We can’t be that hard on Penfield, because the number of cases where he was able to study head movement was quite limited, and studying head motion as he did, by applying an electrode directly to the brain, creates some challenges,” says lead author Buz Jinnah, MD, professor of neurology, human genetics and pediatrics at Emory University School of Medicine. Read more

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Going meta

Just before Thanksgiving, Slate writer Katy Waldman had a piece summarizing the growing body of evidence that linguistic metaphors reflect how we actually use our brains.

Emory neuroscientist Krish Sathian and his colleagues have been major contributors to this field (“conceptual metaphor theory”). In 2012, he and Simon Lacey published their brain imaging study, which found that when people listened to sentences involving touch metaphors (“having a rough day”), the parts of the brain involved in the sense of touch were activated. NPR’s Jon Hamilton talked about these findings with him in 2013.

At the recent Society for Neuroscience meeting, Sathian discussed his team’s ongoing work on how the brain processes metaphors that make references to body parts (head, face, arm, hand, leg, foot), as part of a nano symposium on language.

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Depression imaging test cited as real deal

Tired of hearing neuroscience, and brain imaging in particular, dismissed as trendy and overblown?

In this Sunday’s review section of the New York Times, Nobel Prize winner Eric Kandel cited research by Emory psychiatrist Helen Mayberg and colleagues (published in JAMA Psychiatry) as a good example of research with potential for substantive impact for the treatment of mental illness:

 In a recent study of people with depression, Professor Mayberg gave each person one of two types of treatment: cognitive behavioral therapy, a form of psychotherapy that trains people to view their feelings in more positive terms, or an antidepressant medication. She http://www.raybani.com/ found that people who started with below-average baseline activity in the right anterior insula responded well to cognitive behavioral therapy, but not to the antidepressant. People with above-average activity responded to the antidepressant, but not to cognitive behavioral therapy. Thus, Professor Mayberg found that she could predict a depressed person’s response to specific treatments from the baseline activity in the right anterior insula.

These results show us four very important things about the biology of mental disorders. First, the neural circuits disturbed by psychiatric disorders are likely to be very complex. Second, we can identify specific, measurable markers of a mental disorder, and those biomarkers can predict the outcome of two different treatments: psychotherapy and medication. Third, psychotherapy is a biological treatment, a brain therapy. It produces lasting, detectable physical changes in our brain, much as learning does. And fourth, the effects of psychotherapy can be studied empirically…

National Institutes of Mental Health director Thomas Insel also has commented on the technique’s clinical potential.

“For the treatment of mental disorders, brain imaging Ray Ban outlet remains primarily a research tool, yet these results demonstrate how it may be on the cusp of aiding in clinical decision-making,” Insel said in a NIMH press release earlier this summer.

In addition, author David Dobbs and blogger Neurocritic both delve into the details of Mayberg’s work.

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Alzheimer’s expert weighs in on proposed guidelines

Scans can show beta amyloid, a protein associated with Alzheimer’s disease (right)

For the first time in 25 years, medical experts are proposing new diagnostic criteria aimed at better and earlier detection of Alzheimer’s disease (AD).

The guidelines, proposed by the National Institute on Aging (NIA) and the Alzheimer’s Association, update and revise the current Alzheimer’s criteria with modern technologies and the latest research advances.

According to the Alzheimer’s Association, an estimated 5.3 million Americans have AD, most of them 65 and older. The disease is thought to begin years, possibly even decades, before symptoms are noticeable. But there is no single, generally accepted way to identify the disease in its earliest stages before symptoms are evident.

The new diagnostic guidelines focus on advances in detecting biomarkers for the disease, such as substances found in spinal fluid or appearing on cutting-edge brain imaging scans conducted with PET or MRI.

Emphasis will be on diagnosing early stages of the disease as soon as possible so that patients can take measures to slow the progression or prevent further damage.

Read more

Posted on by Jennifer Johnson in Neuro Leave a comment

Combined MR/PET imaging

On Thursday, April 8, Emory’s Center for Systems Imaging, directed by Department of Radiology Chair Carolyn Meltzer, MD, and the Atlanta Clinical & Translational Science Institute celebrated the launch of the CSI’s prototype MR/PET imaging scanner.

View of MR/PET

View of MR/PET scanner from front, with Ciprian Catana of MGH and Larry Byars of Siemens

The scanner is one of four world-wide and one of two in the United States, and permits simultaneous MR (magnetic resonance) and PET (positron emission tomography) imaging in human subjects. This provides the advantage of being able to combine the anatomical information from MR with the biochemical/metabolic information from PET. Potential applications include functional brain mapping and the study of neurodegenerative diseases, drug addiction and brain cancer.

Thursday’s event brought together leaders of the three other MR/PET programs in Boston, Jülich and Tübingen, the Siemens engineers who designed the device, and the Atlanta research community to explore the possibilities of the technology.

Read more

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Discerning a prelude to Alzheimer’s

Imagine that an elderly relative has been having difficulty remembering appointments and acquaintances’ names, or even what happened yesterday. Memory problems can be signs of mild cognitive impairment (MCI), a prelude to Alzheimer’s disease.

Scientists believe that the outward effects of the slow damage that comes from Alzheimer’s only show up after the damage has been accumulating for years. However, memory difficulties can also be the result of stress or another health problem. Patients thought to have MCI at an initial doctor’s visit sometimes improve later.

That’s why researchers at Emory’s Alzheimer’s Disease Research Center have been testing noninvasive imaging approaches to distinguishing MCI from healthy aging and Alzheimer’s. Their goal is to identify individuals at risk of developing Alzheimer’s, at a time when intervention can make a difference in how the disease progresses.

“We believe that imaging technology may help us find the signature changes in brain structure that are specific to MCI,” says Felicia Goldstein, PhD, associate professor of neurology.

Color coded diffusion tensor image (DTI) of a brain section from a healthy individual (A) showed a thick and intact corpus callosum (orange color), a white matter fiber bundle connecting left and right hemisphere as illustrated in the 3D rendering of the tractograph derived from DTI (B). However, a thin and narrow corpus callosum is seen in an AD patient (C) due to the degeneration of this white matter structure

Color coded diffusion tensor image (DTI) of a brain section from a healthy individual (A) showed a thick and intact corpus callosum (orange color). However, a thin and narrow corpus callosum is seen in an AD patient (C) due to the degeneration of this white matter structure. Courtesy of Hui Mao.

Two recent papers highlight the use of diffusion tensor imaging, an advanced form of magnetic resonance imaging.

The first paper was published by Brain Imaging and Behavior with Goldstein as first author, in collaboration with Hui Mao, PhD, associate professor of radiology, and ADRC colleagues.

It examines diffusion tensor imaging as a way to probe the integrity of the brain’s white matter, and compares it with tests of memory and behavior traditionally used to diagnose MCI and Alzheimer’s.

White matter appears white because of the density of axons, the signal-carrying cables allowing communication between different brain regions responsible for complicated tasks such as language and memory.

Diffusion tensor imaging allows researchers to see white matter by gauging the ability of water to diffuse in different directions, because a bundle of axons tends to restrict the movement of water in the brain.

Goldstein and her colleagues found that patients diagnosed with “amnestic” MCI showed greater loss of white matter integrity in a certain part of the brain — the medial temporal lobe – than cognitively normal controls of similar age. This loss of white matter was linked with poor recall of words and stories.

The second paper, with Liya Wang, PhD, a senior research associate in Mao’s laboratory as first author, was published by the American Journal of Neuroradiology in April. Here the authors try combining probing white matter integrity with a MRI measure of whether the brain has shrunk as a result of disease.

Combining the two methods improves the accuracy of MCI diagnosis with respect to either alone, the authors found.

Mao notes that Emory has been participating in a multi-center study called ADNI (Alzheimer’s Disease Neuroimaging Initiative). Diffusion tensor imaging is a relatively new technique and could add information to future large-scale Alzheimer’s imaging studies, he says.

The Dana Foundation’s BrainWorks newsletter had an article recently on Alzheimer’s and brain imaging.

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