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Anna Greenwald

February 27, 2017

She began her scientific career while studying psychology at the University of Goettingen, Germany (BS 2003, MS 2006). She obtained her PhD in experimental psychology from the University of Giessen, Germany, in 2009. Parts of her doctoral research were performed as a Visiting Scholar at the University of Rochester, NY, and after completing her degree in Germany, she returned to the US for a postdoctoral fellowship in the Department of Neuroscience at Georgetown University Medical Center. She is now a research assistant professor in the Department of Neurology and an affiliate researcher in the MedStar National Rehabilitation Network, and works at the Center for Brain Plasticity and Recovery. Her primary research interest is in cognitive recovery after stroke (especially stroke to the brain’s right hemisphere).

1. Describe your research interests and how you chose this area of research.
I can't remember a time in my life when questions about the brain were not buzzing around in my head. A late only child, I was aware from an early age on of the problems aging adults around me were facing. How could somebody who had known and loved me all my life all of a sudden fail to recognize me? "Dementia," the doctors said. "It's not working right up here anymore," my grandmother said with an apologetic smile, pointing at her head. My uncle had the most careful print-style handwriting I had ever seen from an adult. "That's because he had a stroke and had to re-learn how to write," I was told. Stroke. I would encounter that word again. Somebody torn out of the middle of a healthy and active life by it. Somebody bound to a wheelchair by it. Somebody unable to find words because of it. In all these cases, there was no obvious injury. The problem, over and again, was in the brain. Roughly three pounds of squishy stuff that governs our behavior and defines who we are, how we perceive the world, what we remember and what we forget. Wanting to understand how this worked, why it sometimes ceased to work in very specific ways, and whether there were ways of making it work again, I devoured books about brain and mind, ranging from philosophy to neurology, and ultimately studied psychology.

I discovered my love for designing experiments and realized that rather than just reading up on existing knowledge, I could actively address some of the countless open questions and contribute to the understanding of the brain from which effective therapies for neurological illnesses may be derived. From undergraduate to postdoctoral research training, my studies have covered a broad range of topics from response priming (in which a "prime" stimulus presented so briefly that it is not consciously perceived nevertheless influences behavior) to tinnitus (a usually high pitched and often severely annoying phantom sound perceived by up to 15% of US adults) and have equipped me with a variety of research tools, including functional magnetic resonance imaging (fMRI - a non-invasive way of probing which parts of the brain alter their activation levels when a person engages in specific mental activities). At the Center for Brain Plasticity and Recovery, which brings together researchers and clinicians from Georgetown University and the MedStar National Rehabilitation Network, I am now back at the roots of my research interests and study the long-term consequences of stroke.

The patients I have the privilege of working with have had strokes either very early in life (often at birth) or in adulthood. They and their families have made the most of what the stroke has dealt them, and I am inspired every day by their resilience and determination not to let the stroke limit their lives. Together, we work through hours of questionnaires, assessments, and fMRI scanning to get a detailed picture of how their everyday lives, their cognitive abilities, and their brains have been altered by the stroke. For the individual patient, this can be a very empowering experience, as it identifies not only limitations, but also strengths and avenues towards further improvement. For the scientific enterprise, the collective data of many patients help answer questions such as "Which impairments is a stroke to a particular brain area likely to produce?" "Which cognitive impairments are the strongest predictors of long-term disability?" "To what extent can other brain areas compensate for the loss of the stroke-damaged area, and which areas are particularly suited to taking over which functions?" (The latter question is particularly relevant now that brain stimulation techniques allow selective stimulation or suppression of specific brain areas, and methods for enhancing plasticity in the adult brain are being developed.) Answering these questions is crucial for providing patients and their families with more accurate prognoses, custom-tailored rehabilitation, and assistance in everyday life.

Research at the Center spans a variety of cognitive functions, but my particular interest is in those affected by strokes to the right hemisphere. Among these functions are the ability to recognize emotion from the tone of a speaker's voice, to understand the relative position, orientation, and composition of objects, and to navigate in space. Patients with strokes to the right hemisphere often have trouble directing attention to the left side of space. In extreme cases, particularly right after the injury, this can lead them to completely disregard things that happen to their left, eating only what's on the right side of their plates or shaving only the right side of their faces. In more subtle cases, reactions to things happening on the left side are slowed down, especially if there are also things happening on the right side that capture the patient's attention. While it is intuitive that impairments in these cognitive skills would lead to real-life problems (just imagine trying to cross the street while being unaware of cars coming from your left or unable to judge whether an oncoming bicyclist is headed straight towards you or will pass on the side), resulting mishaps are easily ascribed to the patient being "clumsy" (no surprise as strokes also often result in problems with movement control) or confused. In addition, the patients themselves are often unaware of the extent of their impairment. Thus, while more obvious stroke-related cognitive impairments, such as hemiparesis (weakness on one side of the body) and aphasia (difficulty understanding and/or producing spoken language) are on top of researchers' and therapists' priorities list, the cognitive consequences of right-hemisphere strokes are neither well understood, nor the focus of evidence-based rehabilitation approaches. The goal of my research is to change that.

2. How does GHUCCTS help you to achieve your research goals and advance your career in clinical and translational research? How will the CTSA program help to advance knowledge and treatments for patients with the disease(s) you study?
There are several ways in which being a CTSA scholar makes this research possible.

The first, plain and simple, is money. Functional magnetic resonance imaging is expensive, and developing fMRI tasks that evoke clearly visible activation in an individual brain takes a lot of trial and error. (The brain is highly active all the time, even at rest, and the activation changes associated with a specific cognitive task are comparatively small and hard to see relative to this massive baseline activity. Normally, fMRI researchers combine activation data from many participants to get a stronger activation picture. But the brains of stroke patients all look different, and we don't know whether they are organized the same way. Thus, averaging is not an option - we need activations to be clear in single participants.) The research money I received from the GHUCCTS, and prior to that from a Music for the Mind Young Investigator Award has enabled me to develop and test a battery of fMRI tasks that do not require averaging. This is key to non-invasively studying brain reorganization in stroke patients.

Second, being a CTSA scholar provides me with protected time to develop my own line of research, rather than working on other investigators' projects to support my salary, and trying to do my own research "on the side." Of course most researchers bring in their own salaries through grants, but as a young investigator who is new to this particular area of research, my chances of obtaining one of the "big" extramural grants were slim. The people at GHUCCTS were willing to bet their money on this new investigator's ability to successfully enter and make an impact in the clinical and translational field of stroke research. Over the course of my CTSA scholarship, I can establish myself in the field through publications and conference appearances and obtain the "street cred" required for bringing in my own extramural funding.

Third, the GHUCCTS provides me with the mentoring and learning environment that I need to hone my clinical research skills. As a cognitive psychologist, I came to stroke research with strong background in experimental design, statistical data analysis, and ability to present results. However, I knew next to nothing about recruiting patient populations or the administrative, ethical, and technical hurdles that come with designing a rigorous clinical trial (which is where my research is ultimately headed: I want to develop treatments and test whether they work). The GHUCCTS provides classes and workshops to help me develop these skill, and brings me in contact with mentors and colleagues who excel in clinical research and are happy to share their expertise.

3. Why is it important to have both disciplinary and ethnic/cultural diversity in medical research? How does diversity contribute to your research? How does diversity enhance scientific discovery? (Examples from your own career would be particularly useful)
In general, research results are only applicable to the population from which they were derived. If our research participants are only a small, homogeneous subset of a more diverse population, their characteristics may differ in crucial ways from those of other patients, and what we find to be true in this sub-population may not be true for other sub-populations. Ethnic and cultural background may influence how willing or able patients are to participate in research, to adapt a preventative strategy, or to comply with a certain treatment plan. To ensure that our research results, and the treatments inspired by them, are applicable to and reach all patients alike, we need to be aware of these factors and do our best to account for them.

With respect to my own research, this means ensuring that my participant sample adequately reflects the population of stroke patients. Stroke disproportionately affects African Americans, but research participation in this population is traditionally low, so I need to emphasize recruitment efforts in this direction. In executing the research, sensitivity for diverse backgrounds is key to creating a comfortable environment for the patients and their families. (Can a hijab be worn inside the MRI scanner? Can I ask this young teenager whether she could be pregnant - an exclusion criterion for our study - or is sexual activity something the parents have not discussed yet?) Lastly, when it comes to disseminating research results and (in the future) alerting patients and therapists of potential treatment options, I want to make sure that I reach everybody who may be a stakeholder, not just those who have access to the internet and online research articles.
In all this, I benefit greatly from the experience and diversity of the GHUCCTS community. People at GHUCCTS come and have worked with people from diverse backgrounds. From them I learn what to watch out for and how I can address these challenges.

Alone, a cognitive psychologist with fMRI expertise would not be able to drive this research to success. I depend on colleagues from a variety of scientific disciplines to provide input on relevant aspects of epidemiology, neurology, radiology, neuropsychology, statistics, and rehabilitation medicine. If I don't know how the population of stroke patients is composed, I cannot recruit a representative sample. If I don't know how cerebral blood flow is altered in the vicinity of a stroke, I cannot confidently interpret my fMRI results. If I don't use the appropriate scanning sequences, I might miss subtle tissue changes in the brain areas around the stroke and incorrectly assume that they are intact. If I don't choose the correct neuropsychological tests or don't administer them correctly, I will not get a veridical impression of a patient's cognitive abilities. If I don't know how to account for the numerous confounding variables that come with studying clinical populations in a statistical analysis, I may draw incorrect conclusions. If I don't know what's already being done in cognitive rehabilitation and what is feasible in a rehab setting, I cannot develop better treatment approaches. Without thorough training in the above-mentioned disciplines, I may not even realize what I don't know or fail to account for. Working with colleagues from different disciplines ensures that I am made aware of what I need to learn, and that I have people to learn it from.

4. How does clinical translational research benefit our communities, both directly and indirectly? (Examples from your own research program would be particularly useful)
Put simply, clinical translational research provides the foundation for evidence-based treatments. It takes knowledge resulting from basic science to derive hypotheses about what treatments might work, then systematically tests these treatments in the safest way possible, and ultimately brings the successful treatments to the communities that need them. I can think of no more efficient way to improve public health and well-being.

Without the foundation in basic research, clinical research would be a costly and potentially risky fishing expedition. ("Hey, has anybody tried this drug as a treatment for depression? No? We totally should!") Understanding the basic mechanisms at work allows us to make informed guesses about potential treatments. When testing such a candidate treatment, translational research moves systematically from research bench to patient bedside (often via animal models). This admittedly slow progression ensures that research focuses on treatments that show promise and are shown to be safe at the intermediate steps. This prevents inefficient or unsafe treatments from being tested in humans, which in the best case would be a waste of tax-payer money, and in the worst case could cause deaths. Lastly, by bringing about evidence-based treatments, translational research can close the market for snake oil salesmen who profit from selling inefficient and potentially harmful pseudo-treatments to patients desperate for a cure.

With respect to my own research, taking the translational route means two things. First, my clinical goals have to be informed by basic research, so I carefully examine the status quo before starting to plan interventions. There are brain stimulation techniques available to enhance or suppress the activity of a certain brain area, and drugs that can enhance plasticity in the adult brain. However, blindly applying these in an attempt to enhance stroke recovery could have devastating effects. (What if making the adult brain plastic again means not only that new things can be learned very well, but also that old things are overwritten in the process? Or if stimulating a certain brain area hurts rather than helps stroke recovery?) Thus, I first study naturally occurring variation: Of patients with strokes to the right parietal lobes, which brain areas do the "best recovered ones" use when performing a spatial task? Are there any costs to using this brain area for spatial tasks (e.g., a decline in the function normally performed by this brain area?) These basic science findings will guide treatment development at a later point. Second, my basic research has to be guided by the ultimate treatment goal, and that is defined by the patients and their families. If not for them, I might waste time and money trying to restore a cognitive skill that has no impact on their everyday lives, or developing a treatment that nobody is willing to undergo. By carefully listening to the patients, I learn what is most important to them and what they are willing to try to get it back.