Adhesive cortical device enables artifact-free neuromodulation for closed-loop epilepsy treatment

Epilepsy, a neurological disease that affects more than 65 million people worldwide, is characterized by abnormal electrical hyperactivity in the brain that causes seizures. Interestingly, about 20-30% of all patients are diagnosed with intractable epilepsy that does not respond to standard medications. Surgical resection of the lesions remains a treatment option for these patients, but it is challenging due to the complexity and risks associated with the procedure.

As a less invasive alternative treatment, the concept of neuromodulation has been proposed, which involves directly stimulating damaged tissue with mechanical, electromagnetic, or optical energy to suppress brain hyperexcitability. One promising approach is transcranial focused ultrasound (tFUS), a noninvasive method that stimulates the brain with high precision without causing permanent damage.

For tFUS to be effective in treating epilepsy, it must be paired with a system that can continuously monitor brain activity and adjust treatment in real time. However, existing devices that connect the cerebral cortex to the brain face challenges due to their high stiffness and low shape adaptability, which makes it difficult for them to fit the folded surface of the brain, resulting in poor tissue-device interfaces. Their poor adhesion to the brain surface also means they struggle to deliver accurate brain signals during ultrasound stimulation due to interference from mechanical pressure waves.

To address this challenge, the research team developed the Shape-Morphing Cortical-Adhesive (SMCA) sensor, a soft, flexible device that adheres tightly to the brain surface, providing stable and accurate monitoring of brain activity even during tFUS stimulation. The SMCA sensor is made of a unique combination of materials. It has a catechol-conjugated alginate hydrogel layer that rapidly binds to brain tissue, providing strong adhesion and reducing the risk of movement or detachment. In addition, the device substrate is made of a self-healing polymer that softens and adapts to the curved surface of the brain at body temperature, providing a tight fit and minimizing the risk of signal artifacts.

The team tested the SMCA sensor both ex vivo (outside the body) and in vivo (inside the body), comparing its performance with that of existing devices without adhesive or shape-changing properties. In experiments in a rat model of epilepsy, the SMCA sensor successfully recorded brain activity during tFUS without interference, enabling the real-time monitoring necessary for effective treatment.

Using this innovative sensor, the researchers implemented a closed-loop seizure control system. The system uses the SMCA sensor to detect early signs of a seizure and automatically adjusts tFUS treatment in response. The system effectively suppressed seizures in real time, demonstrating the potential for personalized, adaptive epilepsy treatment.

Professor SON Donghee stated, “Through our research on the soft bioelectronics platform that adheres to the brain, we have overcome a major challenge in the field of brain interfaces by achieving high-quality electrocorticography combined with focused ultrasound stimulation without artifact interference.” He explained the significance of this research and outlined the future plans, adding, “We expect our technology to become the cornerstone of a next-generation biomedical platform that enables precise diagnosis and personalized therapy for incurable neurological disorders. Following this research, we will further develop the SMCA sensor platform by improving the shape-changing and cortical adhesion functions, developing highly integrated microelectrodes, and implementing a higher-order closed-loop operation algorithm.”

Dr. Hyungmin KIM stated, “We achieved early detection of seizure activity using ECoG, which enables seizure prevention. In addition, we implemented real-time feedback on the effects of ultrasound stimulation, which allowed for personalized stimulation protocols. Looking to the future, we anticipate that the development of electrodes with more channels, as well as multichannel ultrasound transducers, will facilitate precise mapping of seizure sources and targeted intervention, ultimately increasing the efficacy and safety of this approach in clinical applications.”

This research was conducted in collaboration with colleagues from Sungkyunkwan University (SKKU) and Korea Institute of Science and Technology (KIST). The results were published in Nature electronics September 11, 2024