Optogenetics Illuminates Cerebellum's Role in Neuroprosthetics

The field of neuroprosthetics, which enables the brain to operate external devices like robotic limbs, is starting to gain traction as a potential treatment option for individuals who are incapacitated by stroke or amputation.

In a study published in the peer-reviewed journal Science Advances, researchers at Cedars-Sinai are believed to be the first to demonstrate how using the cerebellum, a region located at the back of the brain, could enhance patients’ capacity to operate these devices.

Neuroprosthetics have largely tapped the brain’s outermost cerebral cortex. The cerebellum has a well-known role in movement but has been ignored in neuroprosthetic research. We are the first to record what is happening in the cerebellum as the brain learns to manipulate these devices, and we found that its involvement is essential for device use.

Tanuj Gulati, Ph.D., Assistant Professor, Study Senior Author and Researcher, Biomedical Sciences and Neurology, Center for Neural Science and Medicine, Cedars-Sinai

Patients who utilize neuroprosthetic devices have electrodes implanted permanently in the brain, typically within the cerebral cortex region responsible for controlling movement, corresponding to the function the device aims to replace. This method can assist patients in manipulating a computer keyboard, a motorized wheelchair, or a robotic limb.

Gulati and colleagues trained laboratory rats to move a neuroprosthetic tube that delivered water using only their motor cortex activity to study how the cerebellum aids in learning neuroprosthetic control. Researchers recorded the activity of neurons in the motor cortex and cerebellum of the rats through electrodes implanted in those regions of the brain.

We found that activity of the neurons in the cerebellum was coordinated with the motor cortex and that activity in the cerebellum was critical for neuroprosthetic task performance.

Aamir Abbasi, Ph.D., Postdoctoral Scientist and Study First Author, Center for Neural Science and Medicine, Cedars-Sinai

During the trials, researchers selectively silenced various neuron populations in the brains of laboratory rats using a cutting-edge technique known as optogenetics. By introducing light-sensitive proteins into brain cells, optogenetics enables light exposure to regulate the activity of these cells.

Silencing neurons in the outer layer of the cerebellum, where it receives input from other brain regions, resulted in laboratory rats struggling to learn to control the movement of the pipe. Conversely, when neurons deep in the cerebellum, responsible for outward communication from the cerebellum to the motor cortex, were silenced, the rats experienced challenges in maintaining accurate control of the pipe.

These results could help make neuroprosthetics an option for patients with damage to the motor cortex due to brain injury, stroke, or diseases such as Parkinson’s or multiple sclerosis. It’s possible that, eventually, implants in the cerebellar region could be used to help these patients manipulate external devices.

Nancy L. Sicotte MD, Chair, Department of Neurology Cedars-Sinai

Nancy L. Sicotte is also the Women’s Guild Distinguished Chair in Neurology at Cedars-Sinai.

“It’s an exciting era for neuroprosthetics,” said David Underhill, Ph.D., Chair, Department of Biomedical Sciences, Cedars-Sinai.

Underhill said, “There is a lot of buzz about neuroprosthetic technology, but there are still many unsolved problems. This study suggests that some of those could be resolved by involving the cerebellum as well as the motor cortex to help patients gain use of neuroprosthetic devices more quickly and improve their ability to control them accurately.”

Other authors involved in the study include Rohit Rangwani, Daniel W. Bowen, Andrew W. Fealy, and Nathan P. Danielsen.

The American Heart Association provided funding for this work through a postdoctoral fellowship, a predoctoral fellowship, a career development award, National Institutes of Health grants, a National Science Foundation grant, and a postdoctoral fellowship from the Center for Neural Science and Medicine at Cedars-Sinai Medical Center.

Journal Reference:

Abbasi, A., et al. (2024) Cortico-cerebellar coordination facilitates neuroprosthetic control. Science Advances. doi.org/10.1126/sciadv.adm8246