Examining a debilitating neurological disease with brain stimulation

Ataxia is a neurological disease that robs patients of muscle coordination and balance and routinely diminishes quality of life. It can cause chronic pain, lead to involuntary muscle contractions, affect speech and swallowing, and limit mobility. It has no cure.

Alyssa Lyon, a doctoral candidate in Virginia Tech’s Translational Biology, Medicine, and Health Graduate Program (TBMH), believes she may have identified a way to optimize symptom relief in one form of the disease.

She will explore her hypothesis in Meike van der Heijden’s lab at the Fralin Biomedical Research Institute at VTC with a two-year, $50,000 grant from the National Ataxia Foundation.

Lyon’s project examines whether a richer understanding of function and communication between two cell types in different areas of the brain’s cerebellum can improve treatment strategies. The study is important because current brain modulation methods such as direct and alternate current, transcranial magnetic stimulation, and focused ultrasound have shown inconsistent results in other studies.

“The hope is to use a stimulation treatment to modulate this neuronal activity, which in turn would fix cerebellar dysfunction in the disease,” Lyon said. “It wouldn't be a cure, but it would potentially improve a patient’s quality of life.”

Van der Heijden, assistant professor at the institute and Lyon’s mentor, said her project falls in line with growing interest in the cerebellum as a therapeutic target for brain stimulation.

“So far, outcomes have been very variable,” Van der Heijden said. “We wondered, what if this variability can be explained by how neurons in different parts of the cerebellum communicate with each other? Surprisingly, no one had ever really looked at that.”

Most forms of ataxia stem from degeneration of nerve cells in the cerebellum. Lyon’s research focuses on a variant of the disease called spinocerebellar ataxia type 3, in which neurons remain intact, but function and communication in two cell types are affected.

One cell type, Purkinje cells, receives information from the other cell types in the cerebellum and shares that information with cerebellar deep nuclei cells, which transmit the information out to the rest of the brain.

In the form of ataxia Lyon studies, that process is breaking down.

Lyon believes that brain stimulation methods could be more effective at treating symptoms if they could be aimed at areas of the cerebellum where they will have more impact.

Her study uses a preclinical model of the disease in laboratory rodents to examine how the cellular communication is breaking down, then examines the effects of adjusting those brain circuits with neuromodulation depending on the location targets.

“Alyssa is fearless, which is an amazing character trait when learning challenging new techniques and chartering unknown territory,” said Van der Heijden, who is also an assistant professor in Virginia Tech’s School of Neuroscience. “She comes in every day with a quiet determination to do the best work and learn new things about the brain. I believe that this will be key to her project, making a difference.”

Lyon said she’s grateful to the Ataxia Foundation and well-prepared for success.

“The TBMH curriculum has been perfect, and Dr. Van der Heijden has trained me and given me opportunities to share my research,” Lyon said. “FBRI, from my classmates to the faculty, has been incredibly supportive and helpful.”

Lyon developed her interest in neuroscience after watching a beloved grandmother live with Parkinson’s disease, a neurodegenerative disorder she would like to study in the future.

“That's what kind of inspired me to pursue this path and figure out what we could possibly do to help improve patient quality of life,” she said.