Hybrid Graphene Electrodes for Monitoring and Treatment of Epilepsy in Free-Moving Animal Models

A hybrid graphene electrode array developed for the diagnosis and treatment of epilepsy demonstrates effective brain signal monitoring and electrical stimulation, showing potential in reducing seizures in free-moving rats.

Key Highlights

1. Research Question:
   Can a hybrid graphene electrode array provide accurate brain signal monitoring and effective electrical stimulation to diagnose and treat epilepsy in free-moving animal models?
2. Research Difficulties:
   Developing a flexible, high-density electrode array for both precise brain activity recording and stimulation without causing damage.
3. Key Findings:
   The hybrid graphene electrode successfully reduced seizures in free-moving rats with superior signal resolution and lower impedance than traditional electrodes.
4. Innovative Aspects:
   First use of a hybrid graphene/Au/graphene electrode array offering high-resolution monitoring and stimulation in awake animals.
5. Importance of the Study:
   Offers a potential new tool for epilepsy treatment and broader applications in neurotherapeutics.

Introduction to Epilepsy and Current Treatment Challenges

Epilepsy is a neurological disorder characterized by abnormal and excessive electrical activity in the brain, leading to recurrent seizures. These seizures may present as uncontrollable movements, loss of consciousness, and can severely impact cognitive function and overall quality of life. In many cases, epilepsy is not only a physical ailment but also affects the psychological well-being of patients, causing anxiety, depression, and memory impairments.

Symptoms of epilepsy vary across individuals and may include seizures of different types, ranging from mild staring episodes to severe, generalized convulsions. Some individuals may also experience a gradual decline in cognitive abilities and other neuropsychological issues. Early detection and effective management of seizures are crucial to reducing long-term health complications.

The current therapeutic options for epilepsy involve medications like anticonvulsants and other drugs, but they are not always effective for every patient. Furthermore, medical treatments can have adverse side effects. Surgical interventions, including deep brain stimulation (DBS), are also used to manage seizures, but they still have limitations, such as the risk of damage to brain tissue and challenges with targeting specific regions of the brain. There is a growing need for more precise, effective, and non-invasive methods to both diagnose and treat epilepsy in clinical settings.

Research Aim

The primary aim of this research was to develop a novel hybrid graphene electrode array that can effectively monitor brain activity and simultaneously deliver electrical stimulation to treat epilepsy, particularly in free-moving animal models. The research aimed to overcome the limitations of current neurostimulation methods by providing a more accurate and flexible electrode that could capture high-resolution brain signals and provide neurostimulation to suppress epileptic discharges.

The research team consisted of Jeongsik Lim, Sangwon Lee, Jejung Kim, Jeonghoon Hong, Sooho Lim, Kyungtae Kim, Jeongwoo Kim, Sungchil Yang, Sunggu Yang, and Jong-Hyun Ahn, hailing from Yonsei University, Incheon National University, City University of Hong Kong, and Gbrain Inc. This research was published in NPG Asia Materials in 2023 and represents a significant contribution to advancing the field of epilepsy treatment using graphene-based technologies.

Experimental Design and Key Results

1. Experimental Process Overview

• Development of a hybrid graphene electrode array composed of graphene/Au/graphene layers.
• Placement of the electrode array on the cortex of freely moving rats.
• Recording of brain signals from multiple cortical sites using the hybrid graphene electrode array.
• Delivery of electrical stimulation through the same electrode array to treat induced epileptic seizures.
• Testing of the electrode array for long-term stability and biocompatibility.
• Analysis of the recorded data to assess the effectiveness of the stimulation in suppressing seizures.

2. Key Experiments

• Electrode Design and Characteristics
  • Preparatory Work: The hybrid graphene electrode array was fabricated using chemical vapor deposition (CVD)-grown graphene and gold (Au) for enhanced conductivity and stability. The electrodes were designed with a graphene/Au/graphene structure to optimize the signal-to-noise ratio (SNR) and to reduce impedance.
  • Experimental Procedures: A 32-channel hybrid graphene electrode array was placed on the cortical surface of freely moving rats. The electrical impedance of the hybrid electrode was compared with a conventional gold electrode (Au) to assess its efficiency in signal recording and stimulation.
  • Results: The hybrid graphene electrode exhibited significantly lower impedance (91.90Ω) than the gold electrode (839.57Ω at 100 Hz), which allowed for more accurate measurements of local field potentials (LFPs) in the low-frequency range (1–100 Hz), where epileptic signals are typically detected. The hybrid electrode also showed a higher transmittance (70.4%) compared to the gold electrode (5%), making it easier to place and observe during surgery. These findings demonstrate the superior performance of the hybrid graphene electrode in detecting brain signals with high precision.

• In Vivo Brain Recording and Stimulation
  • Preparatory Work: Rats were implanted with the hybrid graphene electrode array to monitor brain activity. Bicuculline was applied to induce ictal-like neural activity and interictal discharges.
  • Experimental Procedures: The brain signals were recorded in vivo to compare the performance of the hybrid graphene electrodes with gold electrodes. Simultaneous electrical stimulation was applied to assess the electrode’s ability to suppress epileptic discharges.
  • Results: The hybrid graphene electrode successfully recorded brain activity with high SNR (51.68 ± 4.45 vs. 5.66 ± 2.54 for gold electrodes). The electrode array detected and precisely recorded epileptic spikes, demonstrating the ability to monitor neural activity at high resolution. Additionally, stimulation via the hybrid electrode array significantly suppressed epileptic discharges and reduced the severity of seizures in the rats. These findings highlight the electrode’s potential for therapeutic applications.

• Long-Term Stability and Biocompatibility
  • Preparatory Work: The hybrid electrodes were tested for long-term stability in phosphate-buffered saline (PBS) at physiological pH (7.4) to simulate long-term implantation conditions.
  • Experimental Procedures: Impedance measurements were taken over a 31-day period to assess degradation and functionality. Immunohistochemistry was used to examine the biocompatibility of the electrode with neuronal and glial cells.
  • Results: The hybrid electrodes exhibited minimal degradation of only 6.69% after 31 days, confirming their long-term stability. Additionally, no significant changes were observed in the number of neurons (NeuN marker) or glial cells (GFAP marker) between the implanted and control hemispheres, indicating the biocompatibility of the electrodes for long-term use.

Conclusion and Implications for Future Research

This research successfully demonstrated that the hybrid graphene electrode array offers a novel solution for both diagnosing and treating epilepsy. The electrode array’s low impedance, high SNR, and ability to deliver electrical stimulation provide significant advantages over traditional electrodes. The study’s findings indicate that the hybrid graphene electrode can not only detect high-resolution brain signals but also suppress epileptic seizures in real-time, making it a promising tool for the treatment of epilepsy.

The authors discussed the limitations of conventional materials used for diagnosing and treating neurological disorders and emphasized the potential of graphene-based materials to overcome these challenges. The hybrid graphene electrode array’s superior electrical conductivity, biocompatibility, and long-term stability position it as a powerful alternative to current neurostimulation methods. The electrodes’ ability to perform both diagnostic and therapeutic functions simultaneously in free-moving animal models represents a significant step forward in the field of epilepsy treatment. Furthermore, the study highlighted the importance of using nanomaterials like graphene in advancing the precision and effectiveness of neural interfaces, offering hope for improved therapeutic options in patients with intractable epilepsy. The findings also suggest that the hybrid graphene electrode could be adapted for use in other neurological conditions, opening up new possibilities for broader applications in neurotherapeutics and neuromonitoring.

Reference:
Lim, Jeongsik, et al. “Hybrid graphene electrode for the diagnosis and treatment of epilepsy in free-moving animal models.” NPG Asia Materials 15.1 (2023): 7.