MRRI Welcomes A New Institute Scientist

Amanda Therrien, PhD

Moss Rehabilitation Research Institute (MRRI) is excited to welcome Amanda Therrien, PhD to our team of exceptional Institute Scientists! In this interview, Amanda shares more about her career path, her research interests, and her experiences setting up her lab at MRRI.

1) Can you describe your career path and the steps that led you to your current position at MRRI?

I did my undergraduate degree in Human Kinetics at the University of Ottawa in Ontario, Canada, which is where I grew up. There I fell in love with the neuroscience of movement control and learning.  In particular, I found the insight that can be gained from studying human behavior fascinating. I decided to go to graduate school to learn more and did my PhD with Drs. Jim Lyons and Ramesh Balasubramaniam at McMaster University in Hamilton, Ontario, Canada.

My research focused on understanding basic mechanisms of sensorimotor control – specifically the control of repetitive, discrete forces and how they are affected by the processing of self-generated (called, reafferent) sensory feedback. Exciting right? Haha, well I thought it was! Importantly, my doctoral training laid a strong foundation of knowledge that inspired questions about how damage to different brain areas disrupts mechanisms of sensory and movement control and how we can use this information to improve rehabilitation training for people with movement disorders. I was especially interested in the effects of damage to an area of the brain called the cerebellum (more on that later). I took these questions stateside and did my postdoctoral training with Dr. Amy Bastian at the Kennedy Krieger Institute and Johns Hopkins School of Medicine in Baltimore, Maryland. With Amy’s mentorship, I learned how to do rigorous patient research and learned the value of designing studies with both basic science and clinical neurorehabilitation goals. I quickly realized that this is what I wanted to do with my career.

I knew about MRRI from some Johns Hopkins alumni that had come to work here in the past. It sounded like a fantastic place to do forward-thinking neurorehabilitation research. So naturally, when I heard they were hiring, I jumped on the opportunity. Thankfully, they also thought that I was a great fit for the MRRI team.

2) What are some of the research questions you are working to address in the field of rehabilitation?

My research interests are guided by 3 broad questions:

(1) How do mechanisms of sensory processing, movement control, and learning differ between low- and high-dimensional movement tasks?

(2) How does the cerebellum contribute to these processes?

(3) How can we leverage this knowledge to develop new rehabilitation therapies?

3) How did you first get introduced to or interested in this field?

I was first introduced to the neuroscience of movement control during my undergraduate degree. While completing my undergraduate honors thesis, I was introduced to ataxia – the disabling movement disorder that results from damage to a brain structure called the cerebellum. People with ataxia have difficulty coordinating their movements, which affects their ability to control their limbs, eyes, balance, walking, and speech. What struck me most about this disorder was that, in most cases, the difficulty controlling movement occurs without any peripheral weakness or peripheral sensory loss. This means that the primary problem is not with movement commands getting down to the body (like you see in cases of stroke affecting the corticospinal tract), nor is it with sensory information getting back up to the brain (like in diabetic neuropathy). Rather, for cerebellar ataxia, the problem occurs when these two signals needed to talk to each other to coordinate movement.

In learning about ataxia I became fascinated with the cerebellum, but I also gained an intense appreciation for the complexities associated with treating the disorder. Currently, there are no widely effective medications for ataxia, so the main course of symptom management is physical therapy. Unfortunately, people with ataxia show highly varied responses to physical therapy, which may be related to cerebellar damage disrupting an important mechanism for learning new movements. Together, these things sparked a strong desire to understand how the cerebellum contributes to sensory processing and movement control as well as the intricacies associated with translating that knowledge to the development of new rehabilitation therapies.

4) Can you describe your work and some of your key findings thus far?

As I mentioned, cerebellar damage impairs a mechanism for learning new movements, called adaptation. Adaptation mechanisms operate continuously as you move around each day. You’ve probably experienced the sensation of needing a few minutes to get used to using the mouse when you switch to a new computer. That’s because adaptation mechanisms in your brain are working to learn the new mapping between the movements your hand makes and the cursor movement you see on the screen. Cerebellum-dependent adaptation uses sensory information to correct movement based on vector errors. In reaching movements, we think vector errors are predominantly estimated using visual information about the difference between the position of the hand and a desired target (e.g. how far and in what direction did the mouse cursor miss the folder you were trying to click on).

My work has studied whether reducing vector error information, by taking away visual feedback during a reach and providing only binary reinforcement signalling (e.g. hit or miss), can reduce reliance on cerebellar processing and improve motor learning in individuals with ataxia from cerebellar damage. These studies have resulted in two main findings. First, people with cerebellar ataxia can take advantage of reinforcement signalling by exploring different movements and retaining reinforced changes to their movement pattern. We have shown this in both the learning of a simple 2-dimensional reaching skill, as well as in a complex 3-dimensional reaching task that had patients learn to correct their reaching ataxia (e.g. they learned to straighten out their normally highly curved and irregular reaching movements). Importantly, these same patients did not learn when provided with visual feedback of vector errors or when given a chance to perform simple repetition (i.e. practice) without reinforcement feedback. The second major finding of this work is that, although intact, cerebellar ataxia patients vary in their learning with reinforcement; on average, learning more slowly than age and gender matched control participants. This is due to cerebellar damage reducing the brain’s ability to estimate the movement that was performed. This makes it harder to map reinforcement feedback to the action that produced it, reducing the efficiency of learning.

5) What is the impact or potential impact of this research?

At the more basic science end of the spectrum, finding that binary outcome feedback, rather than online error information, leads to significant learning and retention in ataxia patients is important for motor learning neuroscience. It suggests that providing less movement information actually improves performance following cerebellar damage. This leads to a number of highly interesting questions about what control mechanisms are at play here. However, closer to the clinical end, finding that binary reinforcement training can be used to improve a high-dimensional aspect of patients’ movement that is directly related to their ataxia raises exciting new possibilities for the development of rehabilitation therapies to ameliorate motor function and quality of life in this patient population.

6) Can you highlight some of the immediate next steps for the research you are doing?

The first step is to understand why binary reinforcement signalling works for people with cerebellar ataxia. One possibility is that reducing the availability of vector error information actually does decrease reliance on cerebellar processing, freeing other neural mechanisms (such as reward-based learning, which is thought to depend more on brain structures like the basal ganglia) to drive a greater share of learning. However, another option is that reinforcement training also prevents people with ataxia from using a problematic, but natural compensation strategy that we call feedback control. To explain this a little bit — sensory feedback about your movements (e.g. vision of where your hand is moving during a reach) is one way for your brain to estimate your movement. However, the brain is slow to process sensory feedback, so relying on it will produce irregular, oscillating movement. This is a large contributor to ataxic tremor. The cerebellum’s crucial contribution to adaptation is in feedforward control – predicting the sensory consequences of a movement command to compensate for time-delayed feedback. I am currently working with Dr. Amy Bastian (Kennedy Krieger Institute and Johns Hopkins) and Ms. Rachel Reoli (a PhD student at University of Maryland) to figure out whether reduced cerebellar reliance, reduced feedback control, or both drove the learning improvement found in my previous work.

Second, I will also be studying how to translate these motor learning results to more complex, real-world movements. The movement tasks studied in my previous research were simple and highly constrained, which was necessary to gain an understanding of the behavioral mechanisms at play. However, there are multiple intricacies that come with moving in more complex ways that will alter how your brain controls and learns movement (e.g. compensation for gravity, increase in degrees-of-freedom, mechanical interactions between joints, etc.). Systematically studying these intricacies will shed light on how reinforcement training may be translated into clinical rehabilitation practice for ataxia.

7) How does your work complement ongoing research at MRRI?

My research adds to the already excellent movement control and learning research programs at MRRI lead by Drs. Dylan Edwards, Laurel Buxbaum, Aaron Wong, and Shailesh Kantak. I bring specialization in mechanisms of cerebellar control of movement, which will be a new field of study for the institute.

8) What has it been like moving to the Philadelphia area and starting to set up your own independent research laboratory?

It’s been a combination of exciting and scary! Haha. Finishing my postdoctoral training and starting my own lab has me looking forward to a new adventure, but like any new chapter in life, there is always a healthy dose of anxiety.

9) What are you most looking forward to in your new position at MRRI? 

Definitely working with and learning from a new group of outstanding neurorehabilitation researchers. I am a firm believer that interdisciplinary collaboration is key for scientific advancement, and MRRI has a fantastic faculty with expertise spanning neuropsychology, speech-language pathology, motor neuroscience, and physiatry.

10) Can you tell us about some of your interests outside of your research?

I like pretty much anything that gets me moving. Given my background in kinetics, this may not be surprising. I am an avid runner, I love yoga, and I enjoy getting out of the city on weekends to go on hiking trips. Once I have adequately exhausted myself though, you will probably find me on the couch, knitting, sipping a cup of tea, and cuddling with a small grey cat named Zooey.

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