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illustration by Emma Vought

Language Lost and Found

New language discoveries inform therapies for aphasia after stroke

by Sver Aune
Illustrations by Emma Vought

Clinical management of aphasia after stroke is being refined with breakthroughs in understanding the networks of language in the brain. Advances in brain imaging show that the dynamically changing neurological environment after stroke can be harnessed to enhance recovery of language in patients with aphasia.

The language impairments of aphasia are observed in nearly a third of all stroke patients.1 Communication is such a vital part of life that its loss after stroke can be personally and professionally devastating.

Leonardo Bonilha, M.D., Ph.D., an associate professor of neurology in the MUSC College of Medicine and director of MUSC’s aphasia clinic, leads a team that is studying how the brain changes after stroke. The researchers seek an understanding of how brain plasticity — the ability of the brain to compensate for areas that are lost to stroke — can support recovery of language in patients affected by aphasia.2 Their hypothesis is that new approaches for aphasia must engage the compensatory potential of brain regions that remain intact after stroke.

Treating the whole brain

Bonilha’s group is using diffusion tensor imaging, which measures white matter tracts, and functional magnetic resonance imaging (fMRI), which displays the areas of the brain that use oxygen during a given language task, to demonstrate that the regions responsible for language are not just unconnected outposts. Rather, they form a continuum, with different regions of gray matter crucial for language connected to one another through a complex network of white matter tracts.3 A specific area of the brain is not solely in charge of one part of speech, then, but relies on concerted interaction with other areas to function.

According to the new neuroanatomy of language, aphasia syndromes are being classified based upon which component of the language process is impaired, in addition to which areas of the brain are affected.4,5 Such an approach examines the brain regions and connections that were lost after stroke and how they determine the symptoms of aphasia. This methodology also reveals the networks that are preserved after stroke and how they support plasticity.2

Traditionally, aphasia has been linked to the location of the stroke lesion in the brain — a method called lesion symptom mapping.4 Specific areas of the brain are paired with the behavior that is lost when that area is damaged by stroke.

“That’s one of the few ways in which you can determine for sure that a brain region is crucial for a behavior,” said Bonilha.

Stroke affecting the left middle cerebral artery (MCA), one of the most important arteries supplying blood to the brain, can cause damage to Broca’s area and lead to Broca’s aphasia, with symptoms of non-fluent, halting speech and difficulty finding words. Other strokes affecting the MCA can cause Wernicke’s aphasia, wherein patients often speak fluently but tend to pepper their sentences with words that have no context or meaning. From these symptoms, Broca’s area of the brain is known to be necessary for word production, while Wernicke’s area is needed for word comprehension.5 The poet Ralph Waldo Emerson suffered what was likely Broca’s aphasia caused by a stroke; on one occasion, he was able to describe an apple but was unable to say the word.6

Advances in neuroimaging with MRI are improving upon traditional models that explore the areas that control language in the brain. When the brain performs a task that engages a certain language step — say, naming an object — it is possible to examine all areas of the brain that are connected — both the gray matter regions affected by stroke and the white matter regions connecting them. One stroke survivor may have damage to several brain areas responsible for breaking down spoken language into thoughts, for example, while another may have damage to brain regions needed to plan the motor functions required to speak.7

Studying all the language regions and how they are connected enables researchers to explore the brain’s connectome, which is the comprehensive map of the entire brain’s wiring pattern and its relationship to communication.3 Bonilha’s research is showing that brain networks are dynamic and adaptive to change — plastic — and that different areas of the brain can be trained by specific speech therapy to compensate for the areas lost to stroke. “We have to understand how the brain processes language and also how the brain changes itself in the context of learning how to speak again,” said Bonilha.

Leaders in aphasia clinical trials

The new neuroanatomy of language is guiding clinical trials designed to place patients in therapy tailored to their specific aphasia. Speech and language therapy remains the standard of care for aphasia, but it is not effective for all patients. There are still questions about how the timing, duration and type of aphasia therapy can affect recovery in different patients.

Research efforts are focused on tailoring speech and language therapies, along with other experimental therapies, to the individual patient. As part of this effort, Bonilha leads the Brain Connectivity Supporting Language Recovery in Aphasia study (NCT02416856). Bonilha’s team will look for specific brain activation patterns that correlate with better recovery of language during speech therapy. The researchers are using fMRI during speech and language therapy to study cerebral blood flow and white matter connectivity in the brains of patients with post-stroke aphasia lasting at least six months.

In a recent high-profile clinical trial, patients who had post-stroke aphasia lasting at least six months experienced significant improvements in verbal communication with three weeks of intensive speech and language therapy.8 Bonilha’s study at MUSC will build on this positive result and serve as a model for testing different speech therapies based on their length, intensity and timing after stroke. In the future, these data could be used to predict which therapy will be most effective in a given patient based upon their initial post-stroke fMRI brain patterns.

“The individual connectome is a very complex, rich dataset, a very complex chart of the patient’s brain,” said Bonilha. “With our research, we can ensure that individual differences are taken into account for recovery.”

In addition to studying the mechanisms of language production in the brain, Bonilha leads the MUSC arm of the Center for the Study of Aphasia Recovery (C-STAR), an $11.1 million program project based at the University of South Carolina (USC) and sponsored by the National Institutes on Deafness and Other Communication Disorders. The center’s goals are to maximize patient recovery from acute or chronic aphasia after stroke. C-STAR’s several research projects enlist stroke and language experts from MUSC, the University of California at Irvine and Johns Hopkins University.

The partnership in aphasia research between MUSC and USC is strategic, since South Carolina is part of the nation’s “stroke belt,” where the incidence of stroke is higher than the national average. Joining efforts in this way is a boon to aphasia research, according to Bonilha. “There’s a network of collaboration within the state that is important,” said Bonilha. “This is a multi-institution, collaborative effort.”

The research partners recently investigated new treatments designed to stimulate the brain during speech and language therapy. The five-year Brain Stimulation and Aphasia Treatment phase 2 clinical trial (NCT01686373) at MUSC and USC assessed whether brain stimulation during speech therapy could improve patients’ performance during language tasks. Patients with post-stroke aphasia lasting at least six months were treated with a method called transcranial direct current stimulation (tDCS), which involves passing a weak electrical current through the brain, along with computer-controlled speech therapy.

The group enlisted the expertise of Mark S. George, M.D., Distinguished Professor of Psychiatry, Radiology and Neuroscience and Layton McCurdy Endowed Chair in Psychiatry at MUSC, and the MUSC Data Coordinating Unit to handle extensive fMRI data processing in the trial. On the basis of preclinical data, the team speculated that tDCS would stimulate patients’ cerebral cortex plasticity and boost their ability to recall words lost to stroke. The promising results of the trial will soon be published.

Bonilha’s collaborator, Julius Fridriksson, Ph.D., SmartState™ Endowed Chair of Memory and Brain Function at USC and principal investigator on the C-STAR grant, is leading C-STAR’s team of researchers. Fridriksson heads the Modeling Treated Recovery From Aphasia phase 2 clinical trial (NCT03416738), which began enrolling chronic stroke patients with aphasia at USC and MUSC in January. In the trial, Fridriksson’s and Bonilha’s teams will examine how biographical factors such as age and gender and factors such as the extent and location of stroke damage affect patients’ abilities to respond to different kinds of speech and language therapy.

“Why is it that some patients respond much better than others to a given type of therapy?” asked Fridriksson. “We are trying to find the best predictors of treatment response in patients.”

In a study with broad implications for future aphasia treatment, Bonilha is working with Chris Rorden, Ph.D., SmartState™ Endowed Chair of Neuroimaging at USC and co-investigator at C-STAR, to evaluate the individual connectomes of patients with acute or subacute forms of aphasia, lasting one month or three months, respectively. Using fMRI, Rorden’s team will obtain data-rich pictures of aphasia patients’ brains during a wide range of speech and language tasks. The goal is to look at the fine-grained structural connectivity of the entire brain after stroke —the location of the stroke damage in gray matter regions as well as the surrounding white matter tracts that have been interrupted.

Language Regained

By working collaboratively with partners in aphasia research, investigators at MUSC are refining clinical care of aphasia by tailoring speech and language therapy to stimulate plasticity in the intact brain after stroke. Data is being used to predict response to treatment, thereby enabling speech therapy to be personalized based on each patient’s brain profile obtained with fMRI and language performance.
The end goals are to help patients regain their social and professional lives. In the future, researchers hope that patients with aphasia can regain their language that was once lost to stroke.

References

1. Engelter ST, et al. Stroke. 2006;37(6):1379-84.
2. Hartwigsen G, Saur D. NeuroImage. 2017;S1053-8119(17):31000-5.
3. Del Gaizo JD, et al. eNeuro. 2017;4(5):e0204-17.
4. Gleichgerrcht E, et al. NeuroImage: Clinical. 2017;16:461-7.
5. Fridriksson J, et al. Brain. 2018. doi:10.1093/brain/awx363.
6. Richardson, R.D. (1995). Emerson: The Mind on Fire. Los Angelos, CA: University of California Press, Ltd.
7. Fridriksson J, et al. Proc Natl Acad Sci. 2016;113(52):15108-13.
8. Breitenstein C, et al. Lancet. 2017;389(10078):1528-38.