Development of implantable devices for epilepsy: research with cats, dogs, and macaques in biomedical engineering

Abstract

In epilepsy treatment, besides medication and surgery, devices that modulate abnormal brain activity are being developed. Intracranial devices like vagus nerve stimulation (VNS), deep brain stimulation (DBS), brain cooling, and drug delivery have seen significant advances in recent years. The process of developing these devices necessitates the use of animals, from the basic to applied research phases. Notably, research with large-sized animals is vital and provides insights that closely mirror human responses. Cats, dogs, and macaques are frequently used models in medicine, neuroscience, and biomedical engineering. However, ethical concerns, escalating costs, and other factors challenge the feasibility of their continued use. Nevertheless, the accumulated knowledge from research on these three species is indispensable for advancing epilepsy treatment techniques. Macaques have brain structures closely resembling humans, offering vital insights into human epilepsy. Meanwhile, cats and dogs present unique study cases. Dogs exhibit high spontaneous epilepsy rates, while established methods exist for inducing experimental convulsive seizures in cats. These devices are increasingly used as therapeutic options for treating domesticated cats and dogs. In this review, we explore research on therapeutic devices for epilepsy in cats, dogs, and macaques, underscoring the importance of these animal models and experimental methods.

GRAPHICAL ABSTRACT

KEYWORDS:

• Epilepsy
• implantable devices
• neuromodulation
• large animals
• ethics

Acknowledgments

We thank Akiko Seki from Yamaguchi University, Ube, Japan, for her valuable assistance with reference checking and figure adjustments. We are also grateful to Dr. Mizuya Shinoyama for their invaluable assistance in illustrating the neuromodulation devices featured in this work. Furthermore, we would like to acknowledge Enago (www.enago.jp) for their professional English language review.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by Japan Science and Technology Agency [grant number JPMJFR2152].

Notes on contributors

Sayuki Takara

Sayuki Takara received her Ph.D. from The Graduate University for Advanced Studies, Okazaki, Japan, in 2008. She is currently researching at Yamaguchi University, specializing in the neurophysiology of the primate brain. Her primary work involves deep brain stimulation (DBS) research using non-human primate models to advance the understanding and treatment of Parkinson's disease.

Hiroyuki Kida

Hiroyuki Kida received his Doctor of Science degree from the Graduate School of Engineering Science at Osaka University, Japan, in 2006. He began his career as an assistant professor at the Graduate School of Medicine, Yamaguchi University, in 2006 and progressively ascended to Lecturer by 2017. His research focuses on the mechanisms of motor learning in the primary motor cortex. He also has research experience with cats and macaque monkeys since graduate school.

Takao Inoue

Takao Inoue earned his Ph.D. from the Kyushu Institute of Technology, Kitakyushu, Japan, in 2008. As an Associate Professor at the Organization for Research Initiatives at Yamaguchi University, he dedicates his research to developing therapeutic devices for neurosurgical disorders, utilizing brain-machine interfaces and neuromodulation. His notable contributions include the development of implantable focal brain cooling devices and multimodality sensing probes to enhance treatments for epilepsy and stroke.