UAB Magazine Weekly - Features on Research
The Key to Manipulating Memories
UAB neurobiologist Farah Lubin, Ph.D., continues to remind scientists to keep an open mind about how the brain functions. She investigates the role of epigenetics—the regulation of genes by environmental factors, rather than by DNA—in the molecular events that lead to long-term memory formation and retrieval. “Epigenetics helps to bridge the two factors we know play a role in our behavior—our genetics and our environment,” Lubin says.
Like Taub, Lubin encountered resistance when she began her research. Scientists had accepted that epigenetic modification could occur during development, but the challenge for Lubin was to show that these mechanisms also occur in non-dividing, mature cells like neurons. Today, her groundbreaking research has convinced most investigators that epigenetics indeed influences the adult brain, allowing humans to adjust to and learn from new environmental situations. “Even in adulthood, you can still change,” Lubin says.
Exposure to new tasks in a social environment is extremely effective in reversing some of the behavioral and cognitive deficits associated with aging, epilepsy, and Alzheimer's disease.
Her lab now is looking for the exact epigenetic mechanisms that allow adults to retrieve old memories and make and store new ones. “Memory is basically who you are, and I think it’s very scary to people to think that they can lose their memory,” Lubin observes. Sometimes, though, the memory of a traumatic event is too much for a person to handle, and it can contribute to declines in physical and mental health. That is why Lubin also is investigating ways to manage epigenetics so that the process can suppress harmful memories.
While much of her research centers on pharmacological ways to manipulate memory, Lubin stresses that drugs are not the only—or necessarily the best—way to enhance neuroplasticity. According to research in her lab and others, mental enrichment, including exposure to new tasks in a social environment, is extremely effective in reversing some of the behavioral and cognitive deficits associated with aging, epilepsy, and Alzheimer’s disease. Unlike drugs, which often have side effects and target only one brain region or molecule, “enrichment seems to incorporate it all,” Lubin says. “I’m interested in this way that nature has given us to handle anything.”
Learn more about epigenetics in this UAB Magazine feature.
Stretching the Limits of Neuroplasticity
By Erin Thacker
Someday soon, we may be able to repair the brain damage from Alzheimer’s, erase traumatic memories, and access untapped reserves of potential in our minds. The key to altering our brains for the better is the insight—just a few decades old—that the brain constantly remodels itself.
Throughout our lives, from infancy to old age, our brains add connections over here, prune others over there, and ramp up production of certain genes while silencing others. As researchers tease out the intricacies of this process, however, they also are learning how to engineer it from the outside.
“Neural plasticity is perhaps the most powerful capacity your brain has,” says David Sweatt, Ph.D., chair of the UAB Department of Neurobiology, director of the Evelyn F. McKnight Brain Institute at UAB, and Evelyn F. McKnight Endowed Chair for Learning and Memory in Aging. “It’s a huge component of what makes us unique, and what makes us so flexible in our ability to adapt in both positive and negative ways to what’s going on around us.”
UAB already is recognized as a global leader in neuroplasticity research, Sweatt says. Now neuroplasticity is listed as a priority in the School of Medicine’s new strategic plan, which helps chart the future of research at UAB. “The brain, generally speaking, and plasticity of the nervous system, more specifically, is one of the last great frontiers in science and biomedicine,” Sweatt says.
Here is a sampling of the intriguing avenues UAB researchers are exploring now.
Desire Makes a Difference: Training the Brain to Repair Itself
In the 1990s, UAB stroke researcher Edward Taub, Ph.D., in collaboration with a group of German investigators, demonstrated that brain plasticity occurs in humans and can have a functional role in sensory experience and movement. He then provided the first concrete evidence that medical treatments can reshape the brain. Over several decades, and despite considerable early skepticism from colleagues, Taub developed constraint-induced movement therapy (CI therapy) to help patients after a stroke. By immobilizing a patient’s functional arm and encouraging the patient to complete tasks with the impaired limb, therapists have been able to produce dramatic results.
CI therapy, originally developed to treat patients after stroke, has been successfully adapted for a number of conditions, including multiple sclerosis.
Brain imaging techniques show that CI therapy leads to “a profuse increase in the gray matter of the brain in motor areas and in the hippocampus,” Taub says. Patients can benefit from CI therapy even if it begins decades after an injury. The therapy requires no surgery or drugs, and there are no side effects. There is one catch, though: Patients must actively participate in their rehabilitation to gain lasting benefits.
“Passive stimulation does not rewire the brain,” Taub says. “Most rehabilitation therapy is, in a sense, passive. People participate, and they move, but they move in response to what the therapist is telling them to do, and their responsibility ends there.”
CI therapy, by contrast, makes patients the key agent in regaining lost motor function by requiring that they continue extensive use of the impaired arm in everyday tasks when they are outside the clinic. “The patients are thereby immersed in a therapeutic environment for a substantial portion of the day,” Taub says. Over the past decade, stroke patients around the world have benefited from the therapy. Taub and his colleagues have successfully rehabilitated patients with traumatic brain injuries and children with cerebral palsy as well.
Now Taub is working with Victor Mark, M.D., an associate professor in the UAB Department of Physical Medicine and Rehabilitation, and Gitendra Uswatte, Ph.D., associate professor in the Department of Psychology, to demonstrate the power of CI therapy in patients with multiple sclerosis (MS).
Unlike stroke or traumatic brain injury, MS is a progressive, degenerative neurological disorder, and at first, Taub and his colleagues weren’t positive that CI therapy would provide any benefit. To their delight, however, MS patients can regain some of their lost function immediately after starting CI therapy, and this improvement persists over time, Taub says.
“If anything, we get a better result with MS than we do with stroke, and for the motor functions we train it has prevented the progress of the motor deficit which normally occurs,” Taub explains. “We seem to be getting the same change in gray matter that we do after stroke as well.” The improvements remain up to five years after treatment—the longest observation that researchers have made so far.
Taub, in collaboration with Margaret Johnson, Ph.D., of the University of Montevallo and Jamie Wade and Leslie Harper of the UAB Department of Rehabilitation’s Speech and Hearing Program, also is seeing benefits in patients with aphasia, a language disorder that can result from brain injury. In the few patients treated so far at UAB, CI therapy seems to be very effective at improving the ability to speak. And in work with psychology graduate student Michelle Haddad, Taub has shown that the therapy increases gray matter in language areas of the brain.
Computer Scientist Uses Language to Fight Crime
By Matt Windsor
olice detectives track criminals using fingerprints.
UAB computer scientist Thamar Solorio, Ph.D., wants to do the same with words. Her research team is bringing artificial intelligence technology to bear on the field of stylometry, which aims to figure out who wrote a piece of text by analyzing word choice and other idiosyncrasies.
“Our goal is to see if we can generate a ‘writeprint’ to identify a document with its author,” Solorio says. The UAB group is developing algorithms that can sift through tiny snippets of style from Twitter updates, Facebook posts, and chat transcripts to discover common elements. Several other research teams are working on automated “authorship attribution,” Solorio notes, but her lab is one of the first to tackle social media.
Solorio’s work, funded by the National Science Foundation and the United States Office of Naval Research, among others, could help identify the authors of terrorist plots from conversations in Internet chatrooms. The same algorithms could also be used to combat cyberbullying among schoolkids and provide valuable information in many other applications, Solorio says. She and fellow UAB researcher Ragib Hasan, Ph.D., are now investigating ways to use authorship attribution techniques to combat a major problem facing Wikipedia—namely, the altering, or defacing, of pages on controversial topics by partisans supporting different sides.
The Clue’s in the Comma
Solorio’s research group, the Computational Representation and Analysis of Language (CoRAL) lab, specializes in natural language processing. This branch of artificial intelligence drives everything from Google’s sorting of search queries to the speech-recognition software used by your bank.
Whether you’re aiming to teach a computer to recognize customers’ voices or a cyberbully’s threats, “you’re trying to design a program that can generalize beyond the examples that you give it so that it can make accurate predictions about new data,” Solorio explains.
The trick is to generate useful predictions when you have only a handful of characters to study—such as the dozen or so words in a typical Twitter post. To succeed, “you need to move beyond word choice and frequency,” Solorio says. “You need to look at syntax, what kinds of word classes are being used, and the length of the sentences, for example. On the Web, you can look at emoticon use and capitalization, too.” Punctuation marks can also hold clues, Solorio says—“there are definite patterns in how people use semicolons, for instance.”
Artificial Conversations Spark Insights into the Evolution of Ideas
By Matt Windsor
Top: Philosopher Marshall Abrams is designing a digital simulation of the flow of ideas among individuals that leads to cultural change.
Above: a representation of the neural networks inside one "person" in the simulation.
In a small office in UAB’s Humanities Building, philosopher Marshall Abrams, Ph.D., is hosting a heated debate about the origins of life. The nine participants share their opinions rapid-fire, completing several hundred conversations every minute. Nevertheless, not a word is spoken; all the action is happening on Abrams’s computer screen. Welcome to philosophy’s digital era.
Abrams is building a computer-based simulation of cultural change, the flow of ideas among individuals that exerts a powerful shaping force on a society’s guiding values. “Meteorologists want to understand the local changes that affect large-scale weather patterns,” Abrams says. “Social scientists want to do the same thing with cultural change. But just like the weather, it is very subtle and complicated. I’m trying to see what a digital model can add.”
Talk Amongst Yourselves
Researchers study the process of cultural change largely through surveys and by tracking books, speeches, films, blog posts, and other recorded artifacts of our collective thought processes. But Abrams, inspired by a growing number of simulations in social science fields, is taking a different approach. Building on software developed by Canadian philosopher Paul Thagard, Abrams has designed a system that lets individual software “agents” talk amongst themselves, sharing their opinions and then responding to the ideas of others by changing their own views.
Innovative Ideas on Preventing and Treating Kidney Stones
By Matt Windsor
The pain has been described as a knife in the back, a body blow, and “the closest thing a man will come to experiencing childbirth.” Whatever the analogy, kidney stones are enormously painful. They often leave victims writhing on the ground.
“They can be excruciating,” says Dean Assimos, M.D., the new chair of the UAB Department of Urology. He speaks from personal experience, having survived two stones himself. And if you live in the South, you’re more likely to know just what he’s talking about.
“The Southeast is the Stone Belt of America,” says Assimos, an internationally renowned expert who specializes in the removal of large stones and preventive measures to avert stone formation. His research group is currently investigating the preventive powers of fish oil supplements and a common gut bacterium. The investigators are also trying to unravel the reasons why stones develop in the first place.
Diet, the hot climate, and genetic factors may be the driving forces behind the high levels of stone formation in the South, Assimos explains. (See "Preventing Stones.") “However, the prevalence of kidney stone formation is also increasing across the country,” he says.
The number of Americans with kidney stones has almost doubled since 1994, according to a study presented at the American Urological Association meeting in May 2012. Researchers speculate that rising obesity rates are a key factor. Whatever the cause, more cases of kidney stones create a burden on the medical system, Assimos says, because treating them usually results in significant health-care expenditures.