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.
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.
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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