Fantastic Voyage

Fantastic Voyage

A 21st-century journey into the brain

We have come a long way since ancient Egyptians believed the heart was the seat of thinking and mental functions—or since the Neolithic Era, when trephination (the process of drilling holes in the human skull) was a commonplace treatment for seizures, migraines, and mental health disorders.

Thanks in large part to advances in imaging techniques, we now have substantive knowledge of how the human brain is organized anatomically and functionally. The amygdala, for example, located deep within the temporal lobe, performs a primary role in the processing of memory and emotions.

Wernicke’s area and Broca’s area, each located in the cerebral cortex, guide our understanding and use of language. Additionally, the development of amazing new techniques such as “brainbow,” which enables researchers to identify individual neurons and trace their activity over time, has expanded our knowledge and understanding of the brain at a cellular level.

It is what lies between the circuitry and the actions that remains elusive. How do cells and synapses come together in an integrated fashion to represent a memory, to form organized speech, or to experience a perception? How do genes and the environment shape the developing brain? What goes wrong to then cause the hundreds of diseases that affect the nervous system, including Alzheimer’s disease and stroke? And, most importantly, how do we use what we have learned to improve health throughout life?

With the help of insightful investigators from multiple fields­—key among them public health—we can begin to understand what triggers disease and/or drives its progression, and why some individuals are more vulnerable to certain diseases than others. The abundance of new information at our fingertips is daunting. But it also represents huge promise, as these studies by U-M SPH researchers show.
Kristen Gibson, MPH ’14

The Three-Pound Giant

The average human brain weighs less than a bag of sugar. But as new public health research reveals, the tiny powerhouse inside our skulls has a huge impact on our health and well-being.

Better Management of Brain Tumor Treatments

Biostatistician Tim Johnson and a team of researchers in the U-M Department of Radiology are analyzing MRI measures in an effort to find quicker ways to determine the efficacy of chemo- and radiation therapies in battling high-grade gliomas, a type of brain tumor. Currently, it takes months to know if a given therapy is working. Johnson and his colleagues hope to speed up that process so that physicians and patients can have results within weeks, not months. It’s potentially life-saving research, Johnson notes, because the sooner physicians know a treatment is not working, the sooner they can alter an existing therapy or introduce a new one.

MS: A Better Understanding

A chronic, often disabling disease, multiple sclerosis attacks the body’s nervous system by damaging nerve fibers and their protective coating. Symptoms can be as mild as numbness or as severe as paralysis or vision loss, and vary depending on the disease subtype. Typically, people with MS must wait months or years before knowing their subtype—but biostatistician Tim Johnson and a team of neuroradiologists hope to change that. By analyzing MRI data from people who have MS and correlating those images with outcomes from two primary functional tests, Johnson and his colleagues hope to find ways to predict MS subtypes so that newly diagnosed individuals know what to expect and can plan accordingly.

Targeted Nanotherapy

Chemo- and radiation therapies attack—and damage—both cancerous and noncancerous cells. But what if a therapy could target cancerous cells only? SPH toxicologist Martin Philbert and U-M’s Raoul Kopelman are developing a nanotherapy consisting of “smart” polymer nanoparticles, or bubbles, that exclusively target cancerous brain tumors in rats. When the solution is injected into the bloodstream, the polymer bubbles bond with the tumors. The scientists then illuminate the tumors with a laser guide. “Within ten minutes all of the cells in the tumor are dead or dying,” Philbert says. “And because the polymer solution is biodegradable, it disappears within hours.”

The nanotherapy has been shown to be effective with cancer cells that don’t respond to conventional therapies. To date Philbert and Kopelman have tested their nanotherapy exclusively on rats; the next step will be clinical trials.

Strokes and Disparities

Through a large population-based study of stroke in south Texas, SPH epidemiologist Lynda Lisabeth is endeavoring to find out why Mexican Americans have higher stroke rates than their non-Hispanic white neighbors. Her recent findings show that even though stroke risk is decreasing in both populations, disparities persist. PhD student Jeffrey Wing is working with Lisabeth to examine potential links between air pollution and stroke risk in both populations. Wing says his findings to date are “suggestive of an association,” and he wants to know whether that association is stronger among Mexican Americans, who may be more susceptible to the effects of air pollution—including particulate matter emitted by nearby oil refineries.

Strokes and Disparities

Through a large population-based study of stroke in south Texas, SPH epidemiologist Lynda Lisabeth is endeavoring to find out why Mexican Americans have higher stroke rates than their non-Hispanic white neighbors. Her recent findings show that even though stroke risk is decreasing in both populations, disparities persist. PhD student Jeffrey Wing is working with Lisabeth to examine potential links between air pollution and stroke risk in both populations. Wing says his findings to date are “suggestive of an association,” and he wants to know whether that association is stronger among Mexican Americans, who may be more susceptible to the effects of air pollution—including particulate matter emitted by nearby oil refineries.

Your Brain on Values

Can core values motivate physical activity? Through a collaborative study led by Emily Falk, assistant professor of communication at the University of Pennsylvania, SPH Professor Victor Strecher and a team of researchers are analyzing brain imagery from individuals who recite their core values while undergoing an MRI. These individuals then participate in a physical activity program. By measuring their physical activity and comparing those measurements to the MRI images, the researchers hope to determine how values motivate physical behavior. Preliminary findings indicate a strong connection. “We’re finding that when people recite their core values, it hits a certain reward center in the brain,” Strecher explains. “That center is a very motivating center—so it stimulates physical activity.”

ALS and Pesticides

The most common motor neuron disease in the U.S., amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease) is a debilitating, ultimately fatal disease. ALS causes motor neurons to degenerate, which leads to muscle weakness and atrophy. SPH Professor Stuart Batterman is conducting a case-control study aimed at confirming an association between ALS and pesticide exposure. “Our study suggests a linkage between past occupational exposure to pesticides and the development of ALS,” he explains. “This linkage has been shown for exposures as far back as 30 years before diagnosis.” Using data from U-M’s ALS Clinic, the researchers are analyzing blood samples for biomarkers of exposure to pesticides, testing for a newly discovered gene that is associated with a small fraction of ALS cases, and examining questionnaires from study participants. If he and his team can confirm the linkage between pesticide exposure and ALS, Batterman says it will provide “one more reason to reduce exposures or reduce the toxicity of chemicals such as pesticides.”

Stress, Brain Function, and Obesity

Early-life stressors can impair long-term brain function, says Alison Miller, who studies the impact of chronic stress on child development and obesity. “If you don’t have a chance to recover from early stressors, your ability to plan and think ahead is less likely to be well developed.” In children who’ve undergone long periods of stress without recovery, Miller and her team have found atypical levels of the hormone cortisol—which is released in response to stress. These same children show higher levels of obesity. Miller theorizes that over time, their biobehavioral stress response becomes “blunted.” She’s working to develop interventions to counteract negative social and environmental factors in children’s lives. “The brain continues to be plastic throughout the lifecourse,” she says. “Even though it may be more difficult to change things later on, it’s possible.”