Aphasia Patients’ Responses to Brain Stimulation May Predict their Extent of Language Recovery – Phase II

Roy Hamilton, M.D.

University of Pennsylvania, Philadelphia, PA

Grant Program:

David Mahoney Neuroimaging Program

Funded in:

April 2014, for 3 years

Funding Amount:


Lay Summary

Aphasia patients’ responses to brain stimulation may predict their extent of language recovery - Phase II

This Phase II study will investigate whether responses by aphasia patients to a form of non-invasive brain stimulation, called transcranial magnetic stimulation, predict their capacity for brain plasticity and recovery of language and motor function.

Aphasia frequently occurs following injury to the brain’s language areas and impairs one or more functions of expressing language, understanding it, and speaking it. About a third of the one million people annually in this country who suffer a stroke develop acute aphasia. Patients’ recovery of language functions is highly variable. It may be influenced not only by the extent and location of brain damage, but also by the degree of the brain’s plasticity, specifically its ability to alter, adapt and develop new connections in language networks.

Recent evidence suggests that assessing the brain’s capacity for this plasticity might be determined by measuring how readily the brain responds to transcranial magnetic stimulation (TMS). If so, TMS could become a biomarker for plasticity, and help to guide choice of the most appropriate rehabilitation strategies.

TMS is a non-invasive method for temporarily manipulating brain activity in a focused way. TMS stimulates the brain when an electromagnetic coil is placed on the scalp and a magnet then creates a rapidly changing magnetic field in the brain. While TMS is ordinarily used to map cortical functions like motor and speech areas, a therapeutic form of TMS also exists. It is called theta burst stimulation (cTBS), and is a powerful form of TMS that can be used to induce temporary targeted and reversible changes in motor functioning and language processing.

Dr. Hamilton and his colleagues anticipate that some people—whether healthy volunteers or patients with aphasia— will show a large response to cTBS stimulation of both the motor and language systems while others will show only a modest response in both systems, depending upon their brain’s capacities for plasticity.

They are testing this hypothesis in a two-phase study designed to 1) determine whether individual differences in cortical plasticity account for differences in responsiveness of language systems to modulation with cTBS; and 2) understand the degree to which the capacity for brain plasticity is a critical determinant of compensatory change in language systems in aphasia recovery. They predict that cTBS-induced changes in motor responses will be strongly associated with similar changes in language performance both in healthy people and those with aphasia. In the Dana-supported Phase I study, the investigators demonstrated the feasibility of enrolling 26 healthy volunteer participants who underwent cTBS in the brain’s motor and language areas. They also have identified 16 post-stroke patients with aphasia to participate in the Phase II study. In this Phase II research, the investigators will enroll an additional 26 healthy volunteers (totaling 42 participants) and a total of 26 aphasia patients. They will determine whether cTBS can predict plasticity of language areas. The researchers temporarily interrupt participants’ normal language function. Then they will assess each individual’s responsiveness to cTBS using a physiologic measure of motor function and see whether this measure also predicts each individual’s responsiveness on language tasks.

They also will explore whether age and a genetic neuronal growth factor thought to influence plasticity also influence motor and language responses. Significance: The study may ultimately result in using cTBS as a biomarker for brain plasticity and in predicting capacity for language and motor function recovery following brain injury.

Investigator Biographies

Roy Hamilton, M.D.

Dr. Hamilton is an Assistant Professor of Neurology and the Director of the Laboratory for Cognition and Neural Stimulation at the University of Pennsylvania. He pursued his undergraduate education at Harvard University, obtaining a BA in Psychology in 1995, and thereafter attended Harvard Medical School and Massachusetts Institute of Technology, where he obtained his MD and a Masters Degree in Health Sciences Technology in 2001. He completed residency training in Neurology at the University of Pennsylvania in 2005 and subsequently pursued a fellowship in Cognitive Neurology, also at the University of Pennsylvania. The central thrust of his research is to use noninvasive brain stimulation to explore the characteristics and limits of functional plasticity in the intact and injured adult human brain. His group uses a combination of behavioral measures and noninvasive brain stimulation techniques, including transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), to elucidate structure-function relationships related to normal cognition and to promote therapeutic reorganization of neural representations of cognitive functions in individuals who have suffered from brain injury.