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Why are opioids addictive?

April 27, 2017 - 4:03pm

The U.S. has a serious opioid problem. In 2014, an estimated 2 million Americans abused opioids, and 91 Americans die every day from an opioid overdose.

Prescribing behavior plays a big role in exposure and often fuels the addiction. Plus, there’s an ample supply to take from. The number of opioids prescribed each year has nearly quadrupled since 1999.

Many people are abusing opioids, and many people are dying from them, but why are opioids addictive? What function in the brain makes us susceptible?

We spoke to Patrick Rothwell, Ph.D., assistant professor in the Department of Neuroscience in the Medical School and MnDRIVE neuromodulation scholar, to answer those questions. He specializes in the neuroscience of addiction.

How do opioids work?

Opioids mimic natural highs caused by chemicals synthesized normally in our own bodies. These “endogenous” opioids are naturally released when we’re happy, or seeing a loved one, or exercising, Rothwell says.

Opiate-based painkillers activate the same receptors. These opioid receptors are found throughout the body, including the brain and the spinal cord. Activation of opioid receptors in different locations leads to the diverse behavioral effects of opiate-based painkillers, such as pain relief, constipation and euphoria.

How do opioids become addictive?

“Opioids target a part of the brain associated with reward and reinforcement processes,” Rothwell said.

Opioid receptor activation increases levels of dopamine in the brain. Dopamine and opioids work together to generate the “high” and encourage drug-seeking behavior. 

Over time the body builds up a tolerance, requiring a higher dose to relieve pain and get high. Prolonged use of opioids can even change the signaling pathways engaged by these drugs.

“If they’re turned on for a long time, feedback mechanisms kick in to constrain activation. That feedback mechanism is what leads to dependence and causes withdrawal.”

Eventually, the body becomes dependent on the presence of an opioid to function normally. Without it, people experience withdrawal which can include vomiting, diarrhea, fatigue, severe sweating and anxiety.

Let’s get into the weeds.

The part of the brain housing reward and reinforcement behavior is called the nucleus accumbens. The nucleus accumbens is home to dopamine receptors: D1 and D2. D1 fuels reward behavior, while D2 establishes aversion. Opioids cause release of dopamine in the nucleus accumbens, which binds to the D1 and D2 receptors and promotes reward.

A recent UMN study from researcher Mark Thomas, Ph.D., associate professor in the Departments of Neuroscience and Psychology, found repeated opioid exposure increased activity to the reward receptor and inhibited the control (or aversion) receptor.

For someone using opioids, this means the brain produces feelings of euphoria when using drugs and suppresses the ability to stop drug use. Someone can even be in recovery, drug-free, and still experience the reward-reinforcement loop because the brain is activated by triggers alone.

Are other prescription drugs addictive that way?

“You don’t get the same physical dependency with other classes of drugs,” Rothwell said.

To put it simply, they’re different. They use different receptors and pathways. Painkillers like ibuprofen or acetaminophen target the peripheral nervous system, comprised of nerves located outside the spinal cord and brain. In addition, the mechanism for pain relief is different. These OTC drugs provide anti-inflammatory benefits without activating opioid receptors.

MORE: How other UMN researchers are developing new non-addictive painkillers and drugs that don’t reach the brain.

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Q&A: The neural switch sparking relapse in addicts

April 14, 2017 - 9:28am

Currently, 24 million Americans struggle with addiction, one of the most common culprits being prescription painkillers. Unfortunately, 80 to 90% of those who overcome this disease face the reality of relapse within the first year of recovery.

The University of Minnesota is driven to fight addiction and improve the lives of those affected by the epidemic.

HealthTalk spoke with Mark Thomas, Ph.D., Associate Professor in the Departments of Neuroscience and Psychology, who is researching the neural switch responsible for sparking intense cravings and causing relapse in recovering addicts.

HealthTalk: What drove you to specialize in this area?

Mark Thomas: My primary area of research is in what we call experience-dependent neuroplasticity; essentially, how does the brain change with experience?

I first specialized in this because of my fascination with how we learn information and how learning experiences change the human brain. As I delved deeper, it seemed like an opportunity to apply this field of study to help others overcome addiction. We know the brain is changing in maladaptive ways because of drug exposure. If we could understand those changes, we can potentially disrupt them to reduce problematic drug use.

HT:  Could you describe the goals and procedures involved in your cutting edge research?

MT: Our research is largely in a mouse model, where we are able to measure changes in the brain related to exposure to addictive substances. After measuring behavior, we introduce a drug free period and then them to stimuli that could provoke a relapse. These stimuli include exposing them to the drugs or similar situations associated with drugs, or creating a moderately stressful experience. In humans, that’s akin to going back to a neighborhood where a person used or seeing drug paraphernalia. These events can provoke intense cravings in addicts. We’re looking at how the brain and the addict’s behavior change with these stimuli, by studying the communication between nerve cells at synapses. The most recent approach we’ve been taking uses light pulse technologies to activate or inhibit highly sensitive neurons in ways that could disrupt relapse behavior.

HT:  How might your work shed light on similarities in drug responses between rodents and humans?

Rodents have a surprising degree of similarity to humans in terms of their neuroanatomy, including the neurotransmitters that communicate between groups of neurons. This is especially true for “reward circuits” that control our natural response to stimuli like food, sex, and building social networks. With resources available here at the U, we’re starting to do brain imaging in rodents that has been done in people for some time. This will help us draw the links between mice and humans for brain changes that contribute to addiction.

HT: What advancements in addiction research do you envision happening within the next 10 years? How do you think the multidisciplinary approach taken by the U of M will contribute to these advancements?

MT: I think there will be advancements in pain medications reducing reliance on these addictive substances. Nonetheless, there will still be plenty of patients who become addicted. For these patients there are some new biology based treatments, like vaccines, destroying drugs in the bloodstream before they reach the brain. Researchers are also working on ways of fine tuning brain circuits to disrupt craving, promoting longer periods free from problematic drug use. My lab collaborates with psychiatry, radiology, pharmacology and medicinal chemistry to work toward making these discoveries. With the Medical Discovery Team on Addiction now forming at the University of Minnesota, we have an opportunity to produce even stronger links between efforts in different departments across the health sciences.

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Prepare to spring forward! Daylight saving begins Sunday March 12

March 10, 2017 - 4:39pm

Daylight saving time is fast approaching- a day many of us dread because it often means losing an hour of sleep.

“While it is only an hour shift, it means that suddenly our community is a little more sleep deprived then we already were,” said Michael Howell, M.D., Associate Professor in the Department of Neurology, Medical School.

This lack of sleep can lead to dangerous situations. A study published by the National Center for Biotechnology Information (NCBI) points out there has historically been a significant increase in accidents for the Monday immediately following the spring shift to daylight saving time. Absenteeism at work and school has also been known to increase in the week following the shift.

“The good news is that this provides us an opportunity to focus more our our bodies natural circadian rhythms, and ultimately sleep better in the long run,” offered Howell.

Some of the ways in which to do that aren’t all that unfamiliar and include:

  • Avoid drinking coffee and other caffeinated/energy drinks in the afternoon as they may lead you to have more trouble falling asleep.
  • While some people notice that they are more likely to fall asleep after having a glass of wine or beer, alcohol leads to more fragmented, less restorative sleep later in the night.
  • While keeping a consistent bedtime can be a good idea, if you can’t fall asleep- stop trying to fall asleep.  Get out of bed and do something relaxing, preferably not in front of a bright screen.  Or if you must, use the Night Shift mode on your phone or tablet computer.  This is found in settings and filters out blue light that is the primary alerting wavelength.

Some helpful steps can actually be taken right when you wake up. If you have trouble waking up in the morning, for example, get some sunlight early.  If it is still dark you can use a 10,000 lux light box.  Those are the same lights used by people with seasonal affective disorder.  Studies have shown that getting some bright light first thing in the morning helps the body adjust to the to the new schedule change, increases alertness and improves mood.

Howell also has some lesser known advice and additional steps we can take to not only help us all get through the upcoming shift, but improve our sleeping habits overall:

  • Melatonin is an over the counter vitamin supplement that taken at least an hour before bedtime can readjust your circadian rhythm so it is both easier for fall asleep at night as well as wake up in the morning. Take in small doses (1mg or less) and allow a few days or weeks for it to take affect (don’t expect it to work immediately).
  • Diets rich in iron (meat, spinach, nuts, olives) especially for young women can help improve sleep.  Iron deficiency can lead to sleep difficulties. Iron is critically important in helping to prevent restlessness which can interfere with a person’s ability to fall asleep at night.

“And if you are still struggling,” Howell said, “it may be time to see a sleep specialist.”

 

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Research Snapshot: Developing a computational model for understanding brain activity

March 1, 2017 - 2:04pm

There are theories for everything. Newton’s Law is a pillar of physics. Supply and demand is a pillar of economics. But what about neuroscience?

“Scientific laws or models organize observations about the world,”said Kendrick Kay, Ph.D., assistant professor in the Center for Magnetic Resonance Research. “We want that for the brain.”

Right now, there aren’t any comprehensive laws in neuroscience. Researchers don’t have a standard to fall back on when interpreting behavior in the brain. That’s due, in part, to the complexity of the brain and the complexity of human cognition which are incredibly difficult to study. With his colleague Jason Yeatman, Ph.D., assistant professor at the University of Washington, Kay has set out to change that.

They’re creating such a mathematical model to analyze the visual cortex, the part of the brain that processes visual stimuli. The visual cortex connects the dots and gives meaning to what the eyes see.

Kay and Yeatman used functional magnetic resonance imaging (fMRI) to measure neural responses in the brain when study participants viewed different images and acted in response to those images. They were particularly interested in a part of the visual cortex involved with functions like reading and face recognition. This area requires both visual stimuli and internal cognition working together.

“Using fMRI experiments, we have developed the first comprehensive model of how this high-level area of the visual cortex works and how humans process visual input,” said Kay.

The data and proposed model were recently published in eLife.

The model has already shown promise in interpreting how the brain represents stimuli, makes decisions about the stimuli, and how neural responses change when the subject is asked to make a decision about those stimuli.

“It’s really quite novel in its scope,” Kay said. “In our field, it’s rare for people to take this modeling approach and we hope others will join.”

Future research could use this model to provide a standard for analyzing data in neuroscience. It could give insight for developing models of other areas of the brain dealing with emotions, language, motor function, other senses and more.

Down the road, it could also help physicians diagnose visual deficits.

“Right now, we can identify that there is a problem: this child has a perceptual disorder. Let’s say they have trouble recognizing faces. With the right brain measurements, our model might allow someone to isolate which specific processes within the brain appear to be functioning abnormally,” Kay said.

That could lead to insight on how certain brain conditions work, and help researchers develop new treatments. Kay and Yeatman plan to continue collaborating on this research direction. They hope to capitalize on the model to understand how children’s brains change as they learn to read, and why some children struggle learning this skill.

The model is still in the very early stages of development. But, Kay and his colleagues are optimistic about the potential. They hope it can be used by neuroscience researchers around the world – not just the University – to better understand the brain.

“This project is a continual endeavor. We will keep developing better and better models and as we do, we’ll get better and better understanding of the human brain,” Kay said.

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Could interactions between brain regions cause Schizophrenia?

November 29, 2016 - 11:56am

In the middle of a conversation with his mom, he glimpsed the figure of a man from the corner of his eye.

But when he turned his head, the figure was gone.

Minutes later, the figure appeared again in his peripheral vision, creating a debilitating sense of concern.

Still, no man was present.

It’s the exact type of visual hallucination some 3 million schizophrenia patients experience.

Scientists don’t know exactly what causes the condition, but a new project led by University of Minnesota Medical School researcher Scott Sponheim, Ph.D., will explore why these episodes of visual distortion occur, potentially leading to improved treatments.

Schizophrenia patients often have difficulty with low-level functions such as basic processing of visual stimuli. They can also have compromised high-level brain functions like attention and memory. So Sponheim will analyze the interaction between the visual cortex and the prefrontal cortex where these low- and high-level functions take place to determine how connected brain regions generate visual distortions.

“Over the past decade, researchers have made huge advances when it comes to mapping connections in the brain,” Sponheim said. “Now we have to understand how alterations in the connections from one part of the brain to other brain regions might explain brain disorders such as schizophrenia.”

Funded by a $3 million grant from the National Institutes of Mental Health, Sponheim will partner with the university’s Center for Magnetic Resonance Research to obtain highly detailed brain images of 150 schizophrenia patients while they perform tasks that prompt activity in the visual and prefrontal cortexes. He’ll also scan the brains of 100 people who are immediate relatives to schizophrenia patients and 50 healthy people who are not related to schizophrenia patients. This data will then be added to the Human Connectome Project repository, serving as a reference for future research.

These images could help researchers better understand healthy brain networks and identify how brain connections may lead to the development of schizophrenia.

Sponheim expects that people with schizophrenia will have abnormal activity in both the prefrontal and visual cortex, while healthy relatives who carry genetic vulnerability for the disorder will only have abnormal activity in prefrontal areas. He thinks the interplay between both abnormalities in the brain causes the hallucinations and represents problems with brain connections that result in schizophrenia.

“By identifying mechanisms for the hallucinations, we can eventually develop more targeted treatments that might improve compromised portions of the brain and improve brain health,” he said. “This research may also point to ways of identifying whether a person could be on the path to developing schizophrenia, so that we can intervene earlier. We hope it’ll be an important building block for mental health research and treatment.”

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UMN researchers will map, study new areas of the brain through improved fMRI technology

October 4, 2016 - 1:00pm

New grants through President Obama’s BRAIN Initiative will allow University of Minnesota researchers to dive deeper into the brain, developing new imaging technology with the potential to map and study neural activity to much greater detail.

The two 5-year RO1 grants from the National Institutes of Health (NIH), totaling $9.4 million, aim to advance functional magnetic resonance imaging (fMRI) technology. MRI measures the structure of the brain, while fMRI allows researchers to also image neural activity by detecting changes in blood flow within the brain.

The Center for Magnetic Resonance Research (CMRR) will lead the research, with collaborations across the Medical School, College of Liberal Arts, and College of Science & Engineering, and with investigators from the Medical University of South Carolina (MUSC).

“Although fMRI has become the most popular neuroimaging tool for studying human brain function, there are still important questions about how well fMRI can ‘see’ inside the brain and what types of underlying neural interactions can be mapped by fMRI,” said Wei Chen, Ph.D., professor at CMRR and principle investigator (PI) of one of the grants. Chen is also a professor in the Medical School’s Department of Radiology.

“We’re excited to get started,”  said Kamil Ugurbil, Ph.D., director of CMRR. “These studies will significantly advance our capabilities for imaging the activity in the human brain, which will improve our ability to diagnose, study and understand various brain conditions.”

Chen’s team will:

  • Develop a new, MRI-compatible, non-metallic high-density electrode array, which can be used to simultaneously stimulate the brain while imaging;
  • The electrode could also lead to MRI-compatible deep brain stimulation (DBS), which has been impossible up to this point because the stimulation devices contain metal;
  • Image areas of the brain with fine spatial scale that have not yet been mapped, including the ‘columnar’ and ‘laminar’ levels

“The high-resolution fMRI uses very high magnetic field scanners at CMRR, allowing us to not only see everywhere in the brain but also able to zoom in to the brain at very high resolution,” Chen said.

Ugurbil will co-lead the second grant with Cheryl Olman, Ph.D., associate professor in the Department of Psychology within the College of Liberal Arts. Their team will utilize fMRI and two-photon optical imaging to:

  • Explore the relationship between blood flow and neural activity to detect changes in brain activity;
  • Study brain activity at a single-neuron level and link it to fMRI signals;
  • Provide much greater specificity to scientists’ knowledge of imaging brain function;

“Utilizing CMRR’s world-leading 10.5 T magnet, as well as similar machines operating at different magnetic field strengths, we will test our hypotheses in model systems,” said Olman. “Once validated, this model will be an important new link between human fMRI and optical imaging studies.”

Findings from both projects could broaden the impact of human brain imaging, leading to potential discoveries related to neurological diseases like Alzheimer’s, Parkinson’s and stroke.

Co-investigators on Dr. Chen’s team include: Ugurbil, CMRR; Xiao-Hong Zhu, Ph.D., associate professor in CMRR; Rajesh Rajamani, Ph.D., professor in the Department of Mechanical Engineering;  Zhi Yang, Ph.D., assistant professor in the Department of Biomedical Engineering; and Esther Krook-Magnuson, Ph.D., assistant professor in the Department of Neuroscience; and Mark Thomas, Ph.D., associate professor in the Department of Neuroscience.

Additional principal investigators on Ugurbil and Olman’s team are: Prakash Kara, Ph.D., associate professor, MUSC; and Thomas Naselaris, Ph.D., assistant professor MUSC. Co-investigators are: Chen, CMRR; Zhu, CMRR; and Essa Yacoub, Ph.D., professor in CMRR.

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Obstructive Sleep Apnea: hidden health crisis in America

August 15, 2016 - 11:37am

A recent study by the American Academy of Sleep Medicine (AASM) revealed obstructive sleep apnea (OSA) could be a hidden health crisis costing America billions.

The study showed there are approximately 30 million Americans suffering from obstructive sleep apnea; yet only 6 million people are officially diagnosed. This means that 80 percent of people with OSA are undiagnosed.

Additionally, the AASM revealed that due to workplace accidents, automobile accidents, comorbid diseases and loss in productivity, the United States is losing a combined $149.6 billion because of OSA.

Michael Howell, M.D., sleep expert and associate professor in the Department of Neurology at the University of Minnesota explained, “This is a critically important study that communicates to decision makers on the costs of sleep problems.”

Howell states that proper treatment of sleep disorders can lead to living happier, being more alert, and performing better at work. Additionally, addressing sleep problems decreases health risks such as heart attacks, strokes, diabetes, obesity, and malignancy.

Other sleep disorders, such as insomnia and restless leg syndrome should also be addressed, says Howell. Treatment of these disorders can have significant mental, physical, and economic benefits.

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Expert perspective: New sleep guidelines for children announced

June 17, 2016 - 2:15pm

Sleep is critical to the overall growth and development of infants, children and teens. But how much sleep is enough? The American Academy of Pediatrics and the American Academy of Sleep Medicine recently released a set of guidelines that outlines how much sleep children should be receiving at different ages.

Infants 4 to 12 months – 12 to 16 hours of sleep every 24 hours (including naps)

Children 1 to 2 years – 11 to 14 hours of sleep every 24 hours (including naps)

Children 3 to 5 years – 10 to 13 hours of sleep every 24 hours (including naps)

Children 6 to 12 years – 9 to 12 hours of sleep every 24 hours

Teens 13 to 18 years – 8 to 10 hours of sleep every 24 hours

Health Talk spoke with Michael Howell, M.D., a neurologist and sleep expert at the University of Minnesota.

“It’s nice to finally have some guidelines,” said Howell. “Parents know that sleep is a moving target, and sleep patterns will evolve over time.”

Howell explained how critical sleep is for children ages 4 months to 18 years old, saying that when children start learning language, math, reading, and social skills, sleep is essential to consolidating all of the information.

Additionally, as children start to enter adolescence, their sleep patterns change and lack of sleep can have consequences in almost every possible way.

“Their grades slip and they tend to have more behavioral issues. There is also a direct correlation between sleep and motor vehicle accidents, substance abuse, teenage pregnancy, and mental health issues.”

Teenagers may also be motivated to know that proper sleep can clear up acne, promote weight loss, and help overall athletic performance.  

Due to the importance of sleep, the idea of delayed school start times has recently been a topic of conversation. Adolescents’ body clocks are naturally later and delayed school start times could allow for more sleep and improve overall mood, academic performance and mental health.

“Sleep consumes one-third of our lives and serves a fundamental purpose in growth and brain development,” explained Howell

Developing good sleep habits at an early age and receiving sufficient sleep can prove to be extremely beneficial and sets the stage for healthy sleep habits later in life.

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Research snapshot: New tools could help prevent relapse behavior in morphine addiction

January 29, 2016 - 12:01pm

Opiate addiction is a crippling problem in society, with an estimated 9 percent of Americans abusing opiates at some point in their life. In Minnesota, opiate overdose deaths have more than tripled since 2000.

Overcoming addiction is extremely challenging, and the risk of relapse persists. A new study from the University of Minnesota Medical School’s Department of Neuroscience identified a potential target for preventing morphine relapse in mice, which brings researchers closer to providing a way for recovering addicts to stay drug-free.

The study, published this month in the Proceedings of the National Academy of Sciences (PNAS), found that manipulating activity of a certain area of the brain could repress relapse behaviors in mice, thereby blocking continued morphine use.

“We’ve identified a specific cell group involved in relapse,” said senior author Mark Thomas, Ph.D., Associate Professor in the Departments of Neuroscience and Psychology. “In our model, we prevented the opiates— in this case, morphine specifically— from triggering relapse behavior.”

The research project by Matthew Hearing, Ph.D., a postdoctoral associate in the Thomas Lab, found that two different types of dopamine-receptive neurons, referred to as D1 and D2, could be driving addictive behavior. They’re located in a part of the brain called the nucleus accumbens, which plays a role in motivation and reinforcement.

It’s believed that D1 receptors encourage rewarding behavior, while D2 stops it. In mice with repeated morphine use, researchers found that D1 activity was persistently increased while D2 activity was reduced. It indicates that these dopamine-receptor cells may trigger relapse.

“Using manipulation to retune D1, we were able to stop morphine relapse,” Thomas said.

Retuning D1 was accomplished through a method called optogenetics. Optogenetics is a fairly new technique in which brain cells are modified to become light-sensitive. Using light rays, a physician or researcher can non-invasively alter brain activity. This was the first time optogenetics has been used as an intervention for opiate relapse. While extremely promising, optogenetics has yet to be translated to humans.

Thomas’ group demonstrated that the antibiotic ceftriaxone also inhibits relapse. While consistent with previous studies, this is the first time researchers have identified ceftriaxone as preventing opiate relapse by inhibiting D1 neurons.

It’s especially crucial to study relapse, Thomas says, because time spent away from drugs reduces an addict’s drug tolerance, while the craving can remain intact. They can be drug-free for decades but the triggers will still be there.

“It’s pretty tough to prevent addiction, but maybe we can stop people from using drugs again,” Thomas said. “Our research identified a target, so let’s continue to research this and develop an intervention to prevent relapse for the millions of people suffering from addiction.”

Thomas’ team will continue to study opiate relapse. He hopes that they can also branch out in the future to apply their findings to other addictions like alcohol, nicotine or barbiturates.

This study was funded in part by the MnDRIVE initiative, which supports brain research and aims to improve the health and quality of life of Minnesotans. The National Institute on Drug Abuse also supported the study.

UMN Researchers Mattthew Hearing, Jakub Jedynak, Stephanie Ebner, Anna Ingebretson, Anders Asp, Rachel Fischer, Clare Schmidt and Erin Larson all contributed to this study.

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In the News: University of Minnesota research drives home aspirin’s benefits

January 12, 2016 - 12:33pm

Despite its known benefits, new research from the University of Minnesota’s Medical School shows many older patients don’t talk to their doctors about the cardiovascular benefits of low-dose aspirin.

The study, published in the Journal of the American Heart Association, looked at aspirin use of 26,000 Minnesotans ages 25 to 74. The study found aspirin use for primary prevention of heart attacks and stroke increased in men from 1 percent in 1980 to 21 percent in 2009, and in women from 1 percent to 12 percent.

In this case, primary prevention means taking aspirin if you have known risk factors of heart attack and stroke, before an adverse event occurs. The recommended age is 45 for men and 55 for women. According to the research, the rate among men 65 to 74 rose from 3 percent in 1980 to 57 percent in 2009, which may not be high enough.

Although people have been using aspirin to prevent heart attacks and stroke since the 1980s, thousands of Minnesotans with high blood pressure are still not using aspirin daily. This is hoped to increase with the “Ask About Aspirin” campaign, lead by researcher Alan Hirsch, M.D., a cardiologist in the Medical School and Lillehei Heart Institute and Russel Luepker, M.D., M.S., professor of epidemiology and cardiology in the School of Public Health.  

“There’s been less clarity and more confusion about what to do when you’re at risk but haven’t had the event [stroke or heart attack],” said Hirsch in an interview with MPR. “In other words, if aspirin is your seat belt, you’d like to wear it before the accident happens.”

The campaign, which launched last year, is an initiative designed by the Lillehei Heart Institute at the University of Minnesota Medical School and the School of Public Health. The statewide campaign is designed to quickly and safely lower heart disease risk by generating public awareness and second, providing the education and tools necessary for health professionals to facilitate the appropriate recommendation.

 

As mentioned in Hirsch’s study, the campaign could potentially prevent 10,000 heart attacks and 1,200 strokes among Minnesotans who currently are at risk. Although increased aspirin use could lead to side effects such gastrointestinal bleeding and hemorrhagic strokes, the low cost and benefits of aspirin outweigh these risks.

“The fear of providing an innocent aspirin pill and causing a bleeding ulcer trumps the optimism of providing something that might prevent heart attack or stroke,” said Hirsch in an interview with the Star Tribune. “It will take a concerted effort to convince doctors and also patients who loathe taking pills when they aren’t sick.”

It’s always important to consult your doctor before taking over the counter medications, so have a conversation about whether it is right for you. Fighting heart attack and stroke could be as simple as taking one aspirin a day.

Related:

Community programs increase aspirin use among individuals at high-risk for heart disease

Some drugs may be off-label, but not off focus

 

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Shining a light on the brain: optogenetics and epilepsy

November 11, 2015 - 9:48am

An estimated 3 million Americans have epilepsy, but most of the fundamental questions about the condition have yet to be answered.

“It’s a really diverse disorder with many different types,” said Esther Krook-Magnuson, Ph.D., assistant professor in the Department of Neuroscience of the Medical School and MnDRIVE neuromodulation faculty scholar. She studies epilepsy in mice, specifically epilepsy affecting the temporal lobe.

Epilepsy manifests itself through seizures. Some may lead to convulsions, while others, like those in absence epilepsy, are non-convulsive and result in a lack of response or a staring-off-into-space effect. But for the most part, why and how epilepsy works remains a mystery.

“That can be very frustrating for patients,” Krook-Magnuson said.

In fact, up to 40 percent of patients don’t achieve seizure control with traditional treatment using medication. Some seek surgical options, like removal of “bad” brain tissue. But that isn’t an option for all patients, including those with bilateral temporal lobe epilepsy, because multiple parts of the brain — including vital portions which work with memory development — contribute to the seizures.

So Krook-Magnuson took a targeted approach using a technique called optogenetics, which uses light to alter brain activity. Software connected to the brain picks up when a seizure happens, and the software triggers light delivery.

Optogenetics takes targeted interventions a step further than other treatments. Not only can scientists detect the seizure area, but they can also target specific cell groups and adjust activity within those cells.

To do this, scientists inject certain proteins to sensitize parts of the brain to light. Depending on the cells and the regions of the brain that are being altered, scientists may be able to cause seizures, worsen ongoing seizures or stop seizures.

“Ideally, we hope to develop a way to target just the cells causing the seizure, selectively inhibiting them or disconnecting them from the rest of the network,” she said.

Her work will help scientists and physicians to better understand brain circuits and how to stop seizures. If translated for use in humans, it could allow physicians to develop specialized treatment plans catered to each individual’s case of epilepsy.

Optogenetics is a fairly new field, only picking up steam in the last five to ten years. It was named “Method of the Year” by Nature Methods in 2010.

“Optogenetics is the tool we’ve been waiting for,” Krook-Magnuson said. “Now we’re asking questions we couldn’t even ask before. The brain is very complex, and we finally have the tools to get some answers.”

Krook-Magnuson’s work researching optogenetics and epilepsy is supported by NIH grant funding and MnDRIVE, a legislative investment in UMN research focusing on brain conditions, robotics, the environment and global food.

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Boo! How the body reacts to fear

October 29, 2015 - 10:08am

In search of Halloween decorations, I make the trek to the vortex of doom basement to sift through storage bins. The stairs creak and the light flickers. The pipes grind and gurgle in an unnatural way, like they have teeth-gnashing souls of their own. The door swings shut violently behind me. Cue the theme from Psycho.

My muscles tighten up, my heart pounds in my chest and I have an overwhelming urge to hightail it out of there.

I know I’m not in danger, but I react anyway.

Why is that?

It’s thanks, in part, to our evolutionary nature.

“Fear initiates our fight-or-flight response,” said William Engeland, Ph.D., professor in the Department of Neuroscience in the University of Minnesota Medical School. “When you’re exposed to a new and potentially frightening situation, our brain perceives it as a threat, and activates an automatic physical response.”

Fear activates a part of the brain called the amygdala, which plays a role in emotional responses. When the amygdala senses something threatening or frightening, it sends a message to the hypothalamus, kicking the adrenal gland into gear to produce more cortisol and adrenaline. That unleashes our sympathetic nerves to promote the “fight or flight” response.

This can lead to several physiological changes:

  • Increased heart rate and blood pressure, to boost blood flow to the parts of the body used for fighting or escaping;
  • Quicker, harder breathing to transport blood and energy more efficiently;
    Increased sweat, possibly to warn off potential attackers with a potent stench;
  • Energy normally spent digesting food switches to target the parts of the body tasked with fighting or fleeing, possibly causing a nauseated or sick feeling;
  • The kidneys and bladder take a break. People often have the sudden urge to use the bathroom when they’re nervous or frightened. That’s because the body is eliminating excess waste to make a getaway easier, and (literally) lighter.

Could someone be scared to death? It’s technically possible. For example, if the body produces too much adrenaline, it could cause a heart attack or stroke. But that’s rare and extremely unlikely, Engeland says.

In general, we need fear.

“These hormones are helpful to our body,” Engeland said. “Cortisol can help with cognition and adrenaline is vital to blood circulation.”

It’s normal to be frightened. It’s how our brains practice for disaster. While the creepy basement is virtually harmless, in the incidence of a true threat (i.e. zombie apocalypse) my body will be ready for a fight. Or, more realistically, a flight.

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Fulbright-Saastamoinen Foundation Grant helps speed up research on Parkinson’s disease, multiple sclerosis and deep brain stimulation

May 29, 2015 - 8:00am

A six-month Fulbright-Saastamoinen Foundation Grant provided a collaboration boost between Shalom Michaeli, Ph.D., professor at the Center for Magnetic Resonance Research (CMRR) at the University of Minnesota and Olli Gröhn, Ph.D., professor and director of the magnetic resonance imaging (MRI) unit and vice director of the A.I. Virtanen Institute for Molecular Science at Kuopio Campus at the University of Eastern Finland.

“During my time in Finland, we made significant progress in establishing MRI biomarkers for Parkinson’s disease (PD) and multiple sclerosis (MS),” said Michaeli. “Noninvasive MRI rotating frame relaxation contrasts developed at the CMRR in close collaboration with the Kuopio team are highly sensitive to slow motion, and could probe critically important processes, such as demyelination, and could serve as noninvasive biomarkers for PD and MS.”

Several joint projects had been initiated and are currently successfully running in collaboration with private companies.

The CMRR is world renowned for its contributions to methodology developments for high field MRI. The magnetic resonance group at the A.I Virtanen Institute under the guidance of Grӧhn has a unique approach of combining expertise in neurosciences and MRI.

While in Finland, Michaeli and his colleagues initiated an additional project using functional MRI (fMRI) and resting state fMRI to test in animals new paradigms for deep brain stimulation (DBS) which are based on modulated electric fields.

“This project is highly innovative and is critical for human health,” Shalom explains.  “We will continue this project both at the CMRR and A.I . Virtanen Institute, combining our efforts and aiming to develop more selective and safer DBS methods.”

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In The News: UMN Psychiatry, MnDRIVE researchers provide non-invasive brain stimulation for treatment-resistant depression

May 11, 2015 - 12:32pm

For nearly 20-30 percent of people who suffer from depression, antidepressants and psychotherapy will not be effective. The depression can be endless and debilitating. Many patients may try multiple medications and therapies with no symptom improvement. They may turn to electroconvulsive therapy (ECT) as a last-resort, which involves inducing seizures to stimulate the brain.

UMN researchers with MnDRIVE are offering a new option which could eliminate the need for ECT for many treatment-resistant depression patients, and would provide considerable improvement in their symptoms.

The non-invasive brain therapy is called transcranial magnetic stimulation (TMS). It uses a magnetic coil within a helmet-like device to stimulate the brain with electric currents. Unlike ECT, TMS has few (if any) side-effects, and does not involve seizures. Brent Nelson, M.D., neuromodulation fellow with MnDRIVE and resident in the University of Minnesota’s Department of Psychiatry spoke with MinnPost about the FDA-approved treatment. The University of Minnesota has the first deep TMS device in the upper midwest. Read his full interview here.

“When people face serious depression, their brain gets stuck. It is hard or sometimes even impossible to get out of the depressive state. What we are trying to do with TMS is to increase the brain’s flexibility to get out of that stuck point,” Nelson told MinnPost.

Patients undergo a month of 20-30 minute sessions with the TMS device, which resembles “old-school hair dryers that you’ll see in a salon,” Nelson said.

TMS is fast and simple for patients. The therapy is virtually pain-free aside from some general discomfort from wearing the helmet.

“There is no memory loss, no negative cognitive effects,” Nelson told MinnPost. “And people are starting to show that there are a lot of positive cognitive effects from these treatments. One theory is that if you are lifting someone’s depression, their mind will clear and their memory will get better.”

Nelson’s team began treating patients last week. He is hopeful that TMS therapy will provide those patients significant improvement in their depression.

The device was made possible through the support of MnDRIVE, a partnership between the University and the state of Minnesota to align local businesses with key research areas, like brain conditions. Suzanne Jasberg, M.D., and Kelvin Lim, M.D., also with the Department of Psychiatry, collaborated on the project with Nelson. Other UMN researchers will use the device in the future to study other neurological conditions, like PTSD and facial pain.

Read the full MinnPost Q&A

Learn more about MnDRIVE

 

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Research Snapshot: A new approach to programming deep brain stimulation for Parkinson’s

March 18, 2015 - 3:46pm

About 100,000 people worldwide undergo deep brain stimulation to treat Parkinson’s disease, dystonia and tremor  when traditional medications or treatments fail to provide symptom improvement or relief. It is also being explored as a treatment for other neurological and psychiatric disorders for which medical therapy has not been effective in alleviating symptoms.

Deep brain stimulation (DBS) involves stimulating portions of the brain through a small implanted device. After the device is implanted, a clinician programs the device to target each patient’s individual symptoms. They establish settings that determine how much stimulation is needed to improve symptoms, a process called programming.

Programming DBS devices can be challenging and requires specialized training and time. Normally, a clinician needs to meet with the patient several times to define a set of stimulation settings that provide optimal improvement in symptoms. Given clinical assessments can be subjective, programming sessions can oftentimes lead to a trial-and-error process.

University of Minnesota researchers may have found an alternative method, which would speed up the programming process for both clinicians and patients with Parkinson’s disease.  It would identify settings more quickly and easily. The findings from this MnDRIVE project were recently published in Parkinsonism and Related Disorders.

“In the past, we’ve had to use qualitative methods, that can be quite subjective, but our new approach uses quantitative measurements to help us refine DBS settings objectively,” said Jerrold Vitek, M.D., Ph.D., a principal investigator on the project, and Chair of the Department of Neurology.

Vitek and Tseganesh Orcutt, N.P., with the University of Minnesota Neurology Clinic, tested a motion sensor device developed by Great Lakes Neurotechnologies, which aims to automate DBS programming. The sensor tracks the changes in tremors and bradykinesia, symptoms of Parkinson’s disease in which the limbs can shake and movements are slowed, as they relate to changes in DBS stimulation settings. A computer algorithm processes that information to establish the best DBS settings for each patient.

In standard procedures, DBS programming sessions can take more than twice as long as a typical evaluation by movement disorder neurologists.

“This is a more efficient and effective approach,” Vitek said. “Patients will make fewer trips for care and in the end we will see reductions in health care costs.”

There is also a shortage of clinicians specially trained in DBS. The new automated approach would give primary care physicians who do not have extensive training or experience with DBS devices a tool that will help them to optimize DBS settings for patients with Parkinson’s disease.

“A DBS specialist will conduct the initial procedure and programming, but afterwards, the fine-tuning could be done anywhere,” Vitek said.

Additional research and development will be conducted before the automated sensor is available for commercial use and distribution, but the outlook is exciting. With this programming approach, Parkinson’s patients could be able to receive treatment closer to home by their own primary care physicians.

“Ultimately, we want to do whatever we can to improve the quality of life for people with Parkinson’s,” Vitek said. “This is one way we hope to accomplish that.”

This research was made possible in part through MnDRIVE, a landmark partnership between the University of Minnesota and the state, which provided a $36 million investment to research advancements in brain conditions, global food ventures, robotics, and the environment.

This study was also funded by an NIH Small Business Innovations (SBIR) grant to Joseph P. Giuffrida, President of Great Lakes NeuroTechnologies in Cleveland, Ohio. Read more.

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In the News: University of Minnesota doctor discusses America’s sleep problems

March 11, 2015 - 11:33am

Oftentimes when people think of the consequences of poor sleep they think crabbiness and irritability. While those are two outcomes of poor sleep, there are many more serious consequences that can occur.

According to the National Sleep Foundation, more than 41,000 Americans are injured or killed in car crashes caused by drowsy drivers. The amount is second to alcohol-related accidents. As stated in the same report, roughly 62 percent of Americans report having trouble falling asleep more than a few nights per week.

University of Minnesota neurologist and sleep expert, Michael Howell, M.D., spoke with Esme Murphy last week on WCCO Radio and WCCO-TV to address the dangers of poor sleep as well as the effects of daylight saving time on sleep schedules.

“Daylight savings brings to the forefront that our culture is a group of poor sleepers. Normally, an hour shift in sleep should not make that much difference. However, for some people it makes for a very hard week as that stolen hour is combined with pre-established poor sleep habits,” said Howell.

Howell says overall, teenagers suffer the most from poor sleep habits.

“Teenagers require 9 hours of sleep which is more than adults require. However, teens typically get less sleep than adults. Teenagers are natural night owls – they like to go to bed later and wake later. This is the same for other mammals going through puberty,” said Howell. “Adolescents from 10-17 have a particular sensitivity to light that sends a signal to the brain that the sun is still up. I see a lot of great kids that can’t fall asleep at 10 or 11 p.m. because their brain still thinks it is 6 or 7 p.m.”

The side effects of poor sleep on teenagers can be serious. Howell says poor academic performance can result. Furthermore, kids that are sleep deprived have a higher tendency to be involved in motor vehicle accidents and a higher tendency for suicide.

There are ways to overcome this shift in circadian rhythms. Howell suggests trying to reset your internal clock.

“Try to minimize screen time an hour or so before bedtime. Force yourself to see sunlight right when you wake up in the morning. If there isn’t a natural sunrise, buy a lightbox. These are designed for seasonal affective disorder. Just 30 minutes of exposure in the morning can help re-start someone’s internal clock,” said Howell.

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Research snapshot: New neuroimaging method to research the aging brain

March 4, 2015 - 8:11am

Testing for age-related metabolic decline and loss of cognitive function could soon be seeing improvements.

By developing new ultrahigh field magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) technologies, researchers at the Center for Magnetic Resonance Research (CMRR) at the University of Minnesota, recently investigated whether new developments could aid in better understanding aging and metabolic disorder in human brains.

Following the establishment of an in vivo assay of nicotinamide adenine dinucleotide (NAD) – a test that works well for human brain application – U of M researchers have developed a new testing technique.

NAD is an essential contributor to metabolism and is found in all living cells, in addition to existing in oxidized (NAD+) to reduced (NADH) forms. Because the redox state ratio of NAD+ to NADH regulates cellular energy production and NAD+ modulates the cellular signaling pathways, both NAD content and redox state are tightly linked to the metabolic or cognitive decline that can occur alongside aging and a range of diseases.

Until now, investigators have been limited by an inability to accurately quantify NAD in vivo (in a living organism), particularly in a living human brain. The in vivo NAD assay technique developed at CMRR allows noninvasive and quantitative assessment of intracellular levels of NAD+ and NADH, and NAD redox state in animal and human brains using an ultrahigh-field MRI scanner. The assay technique proved to be highly reproducible and is sensitive enough to detect age-dependent changes in NAD metabolism and redox state in normal human brain.

So, what does that mean for research into the aging brain?

“This research provides a new neuroimaging modality which is sensitive and specific to the brain energy and NAD metabolisms,” said Wei Chen, Ph.D., radiology professor at CMRR and co-author of the study which was recently published in the Proceedings of the National Academy of Sciences. “It also opens opportunities for understanding normal aging, and studying neurodegenerative diseases and other brain disorders.”

The research team has worked closely with Paul Tuite, M.D., a University of Minnesota movement disorder expert, to initiate a pilot study of Parkinson’s disease (PD) patients using this testing technique.

“This assay offers opportunity for using NAD+ and NADH as biomarkers to track the disease progression and response to drug treatments in the brain, and it could be applied to other organs,” said Xiao-Hong Zhu, Ph.D., associate professor at CMRR and co-author of the study.

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Health Talk recommends: Sleepless in America

December 4, 2014 - 8:30am

In previous posts, Health Talk has detailed the importance of sleep and its many health benefits. A new television series on the National Geographic Channel called “Sleepless in America” along with The Public Good Projects and National Institutes of Health highlights the need for sleep along with some of the “shocking life-threatening consequences of its absence.”

Watch this trailer for more.

According to the trailer, 40 percent of American adults are sleep deprived and adolescents, especially, are most prone to sleep deprivation. And while some examples shown are pretty dramatic, they underscore the necessity and importance of getting enough quality sleep to avoid accidents and tragedies such as the Exxon Valdez oil spill, the Staten Island Ferry crash and the Three Mile Island nuclear meltdown.

“Poor quality sleep leads to numerous cognitive impairments. The consequences range from impaired academic (or athletic) performance to motor vehicle accidents,” said Michael Howell, M.D., University of Minnesota neurologist and sleep expert. “Further, sleep disorders such as insomnia, restless legs syndrome and obstructive sleep apnea often compound sleep deprivation especially among the young.”

Howell says sleep is critical to a healthy central nervous system. The brain is composed of 100 billion neurons and trillions of synapses (connections between neurons). Sleep helps to maintain the normal neuronal and synaptic function of this phenomenal organ.

Sleep deprivation and sleep disorders are common, often misunderstood, identifiable and reversible. By correcting these pervasive problems individuals notice improved brain function, as well as a greater overall health and wellness.

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Research snapshot: Evidence based medicine applications can be applied to well-established interventions

October 29, 2014 - 10:20am

In science and medicine, doctors utilize many kinds of evidence when making health care decisions. Known within the medical community as evidence based medicine (EBM), one of the primary goals is to improve overall decisions by the individual physicians and care team. In a previous study published in the British Medical Journal, researchers argued that some things are so obvious that they do not require ongoing research and even ridiculed the practice of evidence-based medicine.

The example they provided was not needing to judge the effectiveness of a parachute when jumping out of an airplane.

And while that may seem logical because everyone “knows” a parachute helps to improve your chances of survival when jumping from an airplane, EBM can more accurately prove this to be true.

In a recent study published in Neurosurgery, Stephen J. Haines, M.D., co-author and Head of the Department of Neurosurgery at the University of Minnesota, used the British Medical Journal example of the parachute and demonstrated that the application of valid EBM analytic techniques could, indeed, demonstrate that the parachute is very effective in preventing death when one jumps out of an airplane.

“We were able to find a neurosurgical example of an intervention approximately as effective as the parachute,” said Haines. “It turns out that surgical removal of an expanding epidural hematoma in a patient who is deteriorating from it is, in fact, almost equally as effective as a parachute in preventing death.”

An epidural hematoma is a form of traumatic brain injury that occurs due to a hemorrhage between the skull and lining of the brain and is usually associated with a skull fracture. Most cases require rapid evaluation and potential surgical intervention.

Haines believes that this demonstrates that even long established treatments like an epidural hematoma that were never subjected to modern validation techniques (they became common medical practice years before) can be effectively evaluated with EBM techniques.

Haines says it may also be the beginning of trying to determine how big the treatment effect of the intervention must be in order to avoid more rigorous evaluation techniques like randomized clinical trials.

“It is not necessary simply to rely on common sense when evaluating effective interventions. Science can help prove their effectiveness and convince more people of their usefulness,” Haines said.

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U of M, St. Jude Medical partner to tackle Parkinson’s disease, depression

October 14, 2014 - 2:15pm

Editor’s note: This article originally appeared on Inquiry.

University of Minnesota researchers and St. Jude Medical are collaborating to treat some of the most challenging and debilitating movement and neuropsychiatric disorders using deep brain stimulation (DBS), a treatment which uses electrical current to directly stimulate parts of the brain. The project is part of MnDRIVE (Minnesota’s Discovery, Research and InnoVation Economy), a $36 million biennial investment by the state that aims to solve grand challenges in areas that align with Minnesota’s industries, including discoveries and treatments for brain conditions.

MnDRIVE’s ongoing partnership with industry leaders will help to achieve its goals for treatments of brain conditions through neuromodulation, a therapeutic intervention that modulates (or changes) the activity of brain circuits to decrease symptoms and improve function.

“We are excited to be collaborating with St. Jude Medical to identify new and better approaches to delivering DBS therapy for patients with Parkinson’s disease, including, for example, changes in how the pulsed electrical stimuli delivered to targets deep within the brain are patterned, or organized,” said Kenneth Baker, Ph.D., assistant professor of neurology at the University of Minnesota. “We hope not only to improve the direct response of the motor abnormalities to DBS, but also to improve patient care by reducing technological and surgical burdens, such as battery replacements.”

Baker adds that the preclinical research is designed in such a way that improvements in their understanding of how best to treat the motor signs of the disease will provide his team with greater insight into the nature of the disease itself and form the basis for novel approaches or additional refinements down the road. The next steps in their research will include smaller translational studies focusing on human trials and treatments.

“Neuromodulation for the treatment of movement disorders is a therapy on the forefront of modern medicine,” said Eric Fain, group president at St. Jude Medical. “As our company explores the potential of neuromodulation therapy, we rely on collaborative partnerships with research partners like the University of Minnesota to help us advance research projects that push that exploration forward. St. Jude Medical and the University of Minnesota have a long-standing partnership that consistently impacts patient care worldwide, and we’re confident that our partnership will continue to ensure the state of Minnesota is a leader in neuromodulation therapy now and in the future.”

In addition to the pre-clinical work occurring in Jerrold Vitek, M.D., Ph.D.’s, professor and chair of neurology, research lab, MnDRIVE researchers are also collaborating with St. Jude Medical on treating neuropsychiatric disorders with DBS.

“Deep brain stimulation is the most promising new treatment for treatment resistant depression. It is based on the anatomy of depression and targets a specific area of the brain that is overactive in depression,” said Barry Rittberg, M.D., assistant professor of psychiatry at the University of Minnesota. “Some subjects that have been disabled for years have had such good improvement that they have been able to return to work and enjoy life once again.”

Learn more new neuromodulation research and treatments at the University of Minnesota here: MnDRIVE brain conditions.

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