Innovative research to improve standard of care for stroke patients

August 15, 2017
Leonardo Bonilha  talks with Emilie McKinnon as she works at a computer
Dr. Leonardo Bonilha discusses research results with Emilie McKinnon, a researcher in the College of Graduate Studies. Photos by Sarah Pack

It’s hard to adequately describe the value of being able to communicate and its role in expressing a person’s humanity, which is one reason researcher Leonardo Bonilha works so hard to help patients keep that ability.

With two studies recently published, researchers with the Language and Aphasia Clinic at the Medical University of South Carolina are looking into what happens in the brain when people lose the ability to communicate and, more importantly, how to use this information to help recovery.  

Bonilha, a neurologist and researcher at MUSC, says the fact that these publications have come out within such a short time show the importance of this research and the strength of collaborations within the clinic and in research. The multidisciplinary outpatient clinic is dedicated to the diagnosis and long term care of people with language or speech problems. The clinic is staffed with neurologists, nurses and speech and language pathologists with expertise in neurological disorders and communication impairments.

“We have a dynamic group at MUSC composed of clinical speech pathologists, graduate students and research assistants, who are energetically engaged in better understanding how the brain processes language, and how one can recover from the loss of language called aphasia after strokes. We also collaborate very closely with a superb aphasia research laboratory lead by Dr. Julius Fridriksson, professor of Communication Sciences and Disorders at the University of South Carolina’s Arnold School of Public Health. Our labs operate in close concert to achieve the same goals.”   

Aphasia Recovery

One example of that collaboration was the study published today in Scientific Reports-Nature that explored the differences in recovery for people who experience language disturbances or aphasia after a stroke. About 60 to 70 percent of survivors recover their ability to produce language within six months. The other 30 to 40 percent of stroke patients, however, suffer permanent aphasia.

It is still not well understood why this happens, he says. Currently, all doctors can do is give an educated guess based largely on the age of the person and the size and location of the stroke lesion, but the predictions can be frustratingly inaccurate. Some researchers think variations in long term aphasia severity may be caused by an undetected fragmentation or disorganization of brain networks that disrupts the transfer of information in areas that may be far from the lesion itself.

To investigate this theory, Bonilha and other MUSC researchers, working in close collaboration with a team led by Fridriksson, Ph.D, mapped entire brain networks and assessed connectivity in 90 people who had suffered a left hemisphere stroke.

Bonilha says the study demonstrates that the preservation of brain wiring after a stroke is associated with less severe speech problems. Even though strokes tend to occur in one localized brain region, the damage can extend far beyond the stroke area by disconnecting areas that are not directly affected by the stroke.

“In this study, we observed that, by measuring how much these disconnections can alter the normal wiring pattern of the brain, we can explain how impaired someone is in the long run after the strokes. The reasons why someone does not recover after a stroke are not fully understood, and this study directly addresses this problem by demonstrating that the wiring of the remaining brain is one important factor for recovery.”

Language is a highly complex function. To produce speech, distant brain areas must be able to accurately share information and translate it into sounds. The team was able to create connectivity maps into modules and calculate a ‘modularity metric’ for each study participant.

While mapping the functioning of the brain's wiring after strokes has been done before, Bonilha says what is novel about this study is mapping the wiring structure of the entire brain with very high precision (less than a tenth of an inch). “By assessing the whole brain structure, we can have a broader perspective on how much the brain has been impacted by the stroke, and what is preserved. This new method requires a lot of computer power and dedicated computer programs,” he says, adding that Chris Rorden, a Smart State chair and professor in neuroimaging research at the University of South Carolina, is a computational neuroscientist who pioneered some of these approaches with his team. 

portrait of Leonardo Bonilha and Barbara  Marebwa
Dr. Bonilha, right, says MUSC provides a supportive environment for medical research, which attracts bright students, such as Barbara Marebwa, a Ph.D. candidate in MUSC's Department of Neurology.

Added to that are the talents that Barbara Marebwa, a Ph.D. candidate in MUSC’s Department of Neurology and lead author of this study, brings to the table. “Barbara comes to neurology research from a technical imaging background, and so she has a unique ability to combine complex network mathematical models with clinical imaging studies to help us better understand brain networks.”

Bonilha says this is a new approach – there’s currently no measure of brain health. “We talk about small vessel changes but we don’t know how much those affect the network and the brain’s ability to function. It’s a new frontier to have a computational method to calculate how well the brain is functioning by looking at network connectivity and to have a single number indicating that. This may be a useful new metric of brain health, which can help us understand recovery from neurological injury or identify problems in healthy individuals long before clinical symptoms appear.”

Marebwa agrees, adding that more research is needed to reveal the underlying mechanisms behind differences in language recovery. “We think disruption of the network structure might be responsible. So, we wanted to look at how the entire brain was connected after the stroke. Instead of focusing on the damaged region, we looked at areas they still had to work with, and mapped those networks to see associations with their aphasia severity.”

Marebwa says it was surprising that modularity was a better predictor of aphasia severity than some of the other estimates that rely on the size and location of the stroke. “Modularity helps us explain why some patients do better than others with their aphasia recovery. We hope that one day we’ll be able to use it to predict recovery and steer therapies.”

Eventually, network parameters as a measure of brain organization and function may be put to use in other conditions such as dementia. The team already is working on studies in people who have not suffered strokes but do have other chronic conditions that are known to impact brain health. “We’re expanding the application of our imaging calculations to cardiovascular disease, hypertension, and diabetes, to try to see how these conditions may contribute to disrupting brain networks. How that may affect patients’ resilience or recovery,” says Marebwa.

Speech Therapy Study

portrait of Leonardo Bonilha and Emilie McKinnon
Dr. Bonilha says he enjoys learning from graduate students such as McKinnon.

Another study is the article published online on June 19 by Annals of Neurology, which explored the ability of the residual language network in the brain to rebuild itself after a stroke. This characteristic, called structural plasticity, is directly related to how much benefit a patient might receive from speech therapy.

Bonilha says the speech therapy study demonstrated that the parts of the brain that are preserved after a stroke do change in terms of their structure. They “rewire” in response to speech therapy, and this change in the brain is associated with speech improvement.

“This study demonstrates that brain is able to change itself, even at older ages, recover from injury and reestablish functions that were lost with the stroke.”

Lead author Emilie T. McKinnon, an M.D., PhD candidate in MUSC's Department of Neurology, says producing speech is a two-step process. First, there’s selecting the correct word using prior knowledge about objects and their functions (semantics) and then pronouncing it phonetically.

"The current theory is that different parts of the brain house these two processes. If that's the case, these areas have to communicate with each other to produce language. So, the question is, when one of those regions is damaged, how is that connection restored? We looked at the microstructure of one of those connections to try to see what happens when language processing improves."

The study tested eight aphasia patients, all of whom had a single stroke at least one year earlier. The participants underwent four magnetic resonance imaging (MRI) sessions - two before speech therapy and two after. A novel aspect of the study was how the MRIs were conducted and assessed.

The investigators used recent advancements in diffusion-weighted imaging and image analysis that provide greater sensitivity to microstructural white matter changes and can reveal previously hidden differences. This was possible because of collaboration with researchers Joe Helpern and Jens Jensen, from the Center for Biomedical Imaging at MUSC, who are pioneers in the development of newer methods to process MRI data that were used in this study.

Bonilha says McKinnon comes from an bioengineering background, so she was able to translate a sophisticated bioengineering model into something that's clinically useful to better understand how the brain works. "She used improvements in MRI techniques and applied a complex mathematical calculation to the data that came out of the scanner to understand how the brain's structure had changed based on the diffusion of water in that area."

Language disturbances are common after stroke and can manifest as difficulty identifying the correct word to use (semantic problems) and/or difficulty pronouncing words (phonemic problems). 

Bonilha says the study found people got better because their brain network got structurally stronger. "The residual connections got stronger in an area where semantic knowledge is integrated. Phonemics weren't related to these changes."

McKinnon hopes that the findings will ultimately guide therapeutic decision-making. "The goal is to be able to look at an MRI and see where the patient's residual strength is," she says. "If we see that the ventral area is really weak, but the phonemics network is damaged beyond repair, we could recommend semantically-oriented therapies."

This strategy may be useful in other conditions as well. Brain functions such as motor control are also damaged by stroke. "The same microstructural changes would have to happen to recover use of a hand," says McKinnon. "So, you could look for the same results with post-stroke motor rehabilitation and, maybe, beyond stroke, in cases of neurodegeneration or brain damage, such as traumatic brain injury. If we can find a relationship between the network structure and function, then we could use this technique to assess recovery potential and progress."

Bonilha’s research is generously supported by research grants from the National Institutes of Deafness and Other Communication Disorders at the National Institutes of Health and from the American Heart Association. (Dr. Bonilha's Twitter account)

Katharine H. Hendrix contributed to this story.