November Science Shorts: Physics and Medicine

6:45:00 PM

Bridget Menasche, 3rd year PhD candidate in Molecular, Cellular, and Developmental Biology

Once a month during the semester, the BioFrontiers Science Alliance hosts Science Shorts, a series of brief talks around a central theme. The November installment focused on Physics and Medicine, and featured research from the Department of Psychology and Neuroscience as well as the Department of Mechanical Engineering.


The Development of Neural Signatures for Discrete Emotional States – Marianne Redden

“Emotions are complex” might be one of life’s great understatements. But despite the complexity of emotions in both body and mind, researchers like Marianne Redden in the Department of Psychology and Neuroscience are working to unravel them. Identifying emotions sounds like the work of poets and therapists; however, researchers are exploring ways to connect the subjective experience of emotion with something objective and quantifiable. The goal of Redden and others in Dr. Tor Wager’s lab is to identify biomarkers, or “signatures,” in the brain that correlate with certain emotions. Ultimately, if researchers can objectively identify emotions, problems like chronic pain, mood disorders, and addiction will be easier to diagnose and treat.

Previous work in the Wager lab has used functional magnetic resonance imaging, or fMRI, to identify pain signatures in the brain. fMRI is able to measure oxygen levels in different parts of the brain, which is a proxy for activity in a particular region – higher oxygen levels means increased blood flow, indicating more neural activity in that part of the brain. Researchers in the Wager lab showed images to people while in the fMRI, and had them rate how negative the emotions they experienced were. Then, they correlated the reported ratings with the neural activity signatures recorded by fMRI.

Redden’s research extends this work to investigate a much larger range of possible emotional experiences. In order to correlate particular emotions with particular brain signatures, Redden shows people a series of images – from uplifting to frightening to disgusting to delicious – while the fMRI tracks their brain activity. Then, out of the fMRI, she shows subjects the same set of pictures and asks them to rate each one based on many dimensions. She also asks people to describe where in the body they experienced the emotions they describe.

By collecting all of this information, it will be possible to correlate the objective fMRI data on brain activity with the subjective reports of emotion. This will allow researchers to find particular patterns in the brain that are consistent for a variety of self-reported emotions. Redden is particularly interested in being able to distinguish pain from other negative emotions. Once she has correlated the different parts of this data set, she can go back and use the same methods to analyze pain data collected previously in the lab to see if the patterns are distinct between negative emotions and pain.

You can learn more about work done by the Wager lab here: http://wagerlab.colorado.edu/



Molecular Engineering of Microbubble Shells – Dr. Mark Borden

Dr. Mark Borden’s job sounds like a kid’s daydream – making bubbles. But his work on engineering microbubbles the size of red blood cells has the potential to make many a physician’s dreams come true.

Microbubbles consist of a gas core surrounded by a single layer of lipids and other molecules. The microbubbles designed during Dr. Borden’s work are between 1 and 10 millionths of a meter in size and have the ability to move easily through small capillaries in the body, such as the capillary bed of the lung. Because of their small size and gas core, these bubbles scatter sound waves – and serve as excellent contrast agents for ultrasounds. In a standard ultrasound, it is often hard to discern tissue structure and organization in detail. However, using microbubbles as a contrast agent makes it possible to visualize blood flow within an organ or tissue.

Microbubbles can also be used to release a drug or a gene to a particular part of the body. Increasing the intensity of the ultrasound to one particular part of the body can cause bubbles there to burst, releasing both the gas and any cargo packaged inside.

Dr. Borden’s team in the Department of Mechanical Engineering is working on many possible applications of this technology. They’re particularly interested finding combinations of gas cores and lipid shells that give microbubbles unique and useful properties. One goal is to vary the stability of the microbubbles by changing the elasticity of the bubble. Like a spring, microbubbles have a resonant frequency, and this affects the kind of response possible. By changing the lipid shell surrounding the gas core of the bubble, it’s possible to manipulate the elasticity and resonant frequency. This is because lipids of different sizes or with different chemical properties change the forces acting within the lipid monolayer surrounding the gas core.

Researchers on Dr. Borden’s team focus on mathematical modeling of microbubble properties and on high-resolution imaging to confirm their calculations. They’re able to make single bubble measurements to determine the resonant frequency and elasticity of bubbles with different lipid monolayer compositions.

One application of this research is the use of microbubble mixes for high-resolution ultrasound imaging. In a way similar to using different colored dyes or different  fluorophores in fluorescence microscopy, bubbles with different elasticities could soon be used to look at the co-localization of different molecules in the body, or to create greater specificity for drug delivery or gene therapy.

You can learn more about work in the Borden lab here: http://spot.colorado.edu/~mabo4929/index.html

And read an open-access review by Dr. Borden about microbubbles here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2889676/



Studying Spontaneous Parkinson’s Symptoms to Predict Psychosis in Youth at High Risk – Derek Dean

Psychosis is often described as a loss of contact with reality, with symptoms including hallucinations, delusions, and theories of external control. Treatment for psychosis is often intensive and challenging, and the drugs used can have severe side effects. In order to make treatment efficient and effective, researchers like Derek Dean are focused on making diagnosis more accurate. Dean is a graduate researcher in the Adolescent Development and Preventative Treatment (ADAPT) Program with Dr. Vijay A Mittal. The primary goal of the ADAPT program and associated research is to identify which high risk adolescents will go on to develop psychosis.

One interesting aspect of treating young patients at high risk for psychosis is that apparent mental symptoms can sometimes be accompanied by movement symptoms. Some young patients show symptoms like Bradykinesia, or slow movement, that are associated with Parkinson’s disease.

But perhaps these unusual symptoms will serve as a useful tool. Dean and other researchers are investigating methods to catch these movement abnormalities earlier, before psychosis sets in. One such method is handwriting analysis – looking at the task of writing loops for speed and consistency. If the movement abnormalities are associated with subsequent onset of psychosis, they could potentially be used as a straightforward, low-cost method for early diagnosis. By drawing on other data collected through the ADAPT program, such as structured clinical interviews that characterize the mental health status of the patients, Dean can identify correlations between symptoms that are quantifiable through handwriting tasks and the symptoms usually used to diagnose psychosis.

In order to determine which brain regions might be involved, Dean has also used fMRI to look at brain volume and functional connectivity. The neurodevelopment model of psychosis proposes that early insults to the brain lead to vulnerability that can be brought out by stressors during adolescence. In order to determine if variation in brain structure is correlated with aspects of psychosis or the associated movement abnormalities, Dean has focused on the cerebellum and the striatum. As described in a recent Clinical Psychological Science paper, he observed altered substructures in the cerebellum and striatum of high-risk patients, and found that these structural differences were correlated with performance on the handwriting task.

Ultimately, Dean’s research contributes to our understanding of what happens before psychosis – and identifies a few possible features that could be used for early diagnosis.

You can learn more about ADAPT here: http://www.adaptprogram.com/about-us/

And you can read more about Dean’s work on cerebellar morphology and psychosis risk here:

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Want more Science Shorts? Come to the January Shorts on Planets and Life! Stay tuned to our Facebook and Twitter feeds for a date and location.

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