Newfound Benefits of Stimulating the Cerebellum at 13 Hz

Beta-frequency (13 Hz) deep brain stimulation of the cerebellum may help ataxia.

Posted Feb 27, 2021 | Reviewed by Kaja Perina

 Life Sciences Databases/Creative Commons (CC-BY-SA-2.1-jp)
Cerebellum (Latin for "little brain") in red. Cerebellar means "related to the cerebellum."
Source: Life Sciences Databases/Creative Commons (CC-BY-SA-2.1-jp)
  • Beta-frequency deep brain stimulation (DBS) into the cerebellum improves motor movement and coordination in mice with ataxia-like deficits, a new study reports.
  • 13 Hz deep brain stimulation delivered to the cerebellum improves coordinated muscle movements in a mouse model (Car8) of hereditary ataxia.
  • Cerebellar DBS normalizes muscle activity during locomotion and induces long-lasting motor benefits in Car8 mice.
  • Combining physical activity on a treadmill with DBS at 13 Hz into the cerebellum enhanced this treatment's efficacy.

Ataxia describes the lack of voluntary muscle control required to perform coordinated movements. In Greek, "a táxis" means "without coordination," which is the root of the medical term "ataxia." Because the so-called "little brain" plays a vital role in coordinating voluntary movements, ataxia and cerebellar dysfunctions—or damage to certain regions of the cerebellum—tend to go hand in hand.

As a neurodegenerative disease, ataxia results in the progressive loss of someone's ability to perform fluid and coordinated movements with their legs, arms, hands, fingers, eyes, etc. Complications from ataxia can be debilitating and, in some cases, lead to premature death.

New research in mice shows promise for rescuing coordinated movements in a mouse model (Car8) of ataxia using deep brain stimulation into the cerebellum's nuclei at a beta-wave frequency of 13 Hz. This peer-reviewed study (Miterko et al., 2021) was published on February 26 in the open-access journal Nature Communications.

This study was conducted by a team of researchers at Baylor College of Medicine and Texas Children's Hospital led by first author Lauren Miterko, a postdoctoral fellow in Roy Sillitoe's lab at Baylor.

"Here, we demonstrate the potential benefits of DBS in a model of ataxia by targeting the cerebellum, a major motor center in the brain," the authors explain. "We use the Car8 mouse model of hereditary ataxia to test the potential of using cerebellar nuclei DBS plus physical activity to restore movement."

Notably, this DBS treatment was greatly enhanced when the 13 Hz cerebellar stimulation was administered while the genetically engineered mice with an ataxia-like condition were "waddling" on a treadmill. "We show that cerebellar DBS restores motion in ataxia and that the rescue of motor behavior was the greatest when the treatment is paired with exercise and starts early after the onset of ataxia," the authors note in the paper's introduction.

"We first targeted the cerebellum because it's a primary motor center in the brain, and this target location for DBS has seen encouraging success for treating motor problems that are associated with other conditions, such as a stroke," Miterko said in a news release. "We systematically targeted the cerebellum with different frequencies of DBS and determined whether there was an optimal frequency that would boost the efficacy of the treatment. When we used a particular frequency, 13 Hz, that was when motor function improved in our Car8 mice."

"We know that exercise, in general, can benefit both muscle and neuronal health, and previous work in Parkinson's disease and stroke patients mentioned that neuromodulation techniques combined with physical stimulation showed benefits, so we decided to include exercise in our investigation," Miterko added. "We found that when the [Car8 mice] received DBS during exercise on a treadmill, there were improvements in motor coordination and stepping that we had not observed with deep brain stimulation alone."

Interestingly, for the combination of 13 Hz stimulation into the cerebellum combined with physical activity to rescue movement and coordination in a mouse model of ataxia, the mice needed well-functioning Purkinje cells.

The researchers found that genetically eliminating Purkinje cell neurotransmission from the cerebellum up to the cerebral cortex via the cerebello-thalamo-cortical pathway blocked the ability of cerebellar DBS to reduce ataxia. "One of our goals is to further elucidate the role Purkinje cells play in recovering from ataxia," coauthor Meike van der Heijden said in the news release.

Side note: This particular aspect of the study stood out to me as an athlete because I've long associated robust Purkinje cell functions with the optimization of perfectly-timed motor movements and the "superfluid" muscle coordination required for peak performance in sports. On a continuum, ataxia and superfluidity are on opposite ends of the spectrum. (See "My Decades-Long Quest to Decode a Quirky 'Super 8' Brain Map.")

From my perspective, another particularly eye-opening aspect of Miterko et al.'s latest paper is that stimulating the cerebellar nuclei at 0, 2, 13, and 130 Hz frequencies seems to support distinct aspects of cerebro-cerebellar circuit function.

"For instance, delta- and theta-frequencies between 1 and 9 Hz promote cerebellar learning at climbing fiber-to-Purkinje cell as well as parallel fiber-to-Purkinje cell synapses," the authors explain. "In contrast, beta-frequencies from 10 to 30 Hz facilitate communication in the cerebello-thalamo-cortical pathway, and higher frequencies between 30 and 260 Hz promote scaling, planning, and neural synchronization."

"We are particularly excited about the results of this study because it may be possible to extrapolate our approach for treating not only other motor diseases, but perhaps also non-motor neuropsychiatric conditions," senior author Roy Sillitoe concluded.

Increasingly, motor and non-motor functions of the cerebellum are being recognized and researched. It will be interesting to see if future studies identify any specific cognitive implications associated with stimulating the human cerebellum at a beta-frequency of 13 Hz.

References

Lauren N. Miterko, Tao Lin, Joy Zhou, Meike E. van der Heijden, Jaclyn Beckinghausen, Joshua J. White & Roy V. Sillitoe. "Neuromodulation of the Cerebellum Rescues Movement in a Mouse Model of Ataxia." Nature Communications (First published: February 26, 2021) DOI: 10.1038/s41467-021-21417-8