Design and Development of Implantable Electrode Arrays for Recording Signals from Rat’s Brain

Abstract

Seizure is a neurological disorder due to abnormal, excessive, and hypersynchronous discharges from an aggregate of central nervous system neurons. Epilepsy describes the clinical phenomena of a condition of recurrent and chronic seizures. Epilepsy is one of the most common neurological disorders globally, with approximately 50 million epileptic patients. About 10 million people (~20% of the total) have epilepsy in India. Antiepileptic drugs (AEDs) are available for treatment; however, these drugs are not epilepsy specific. Moreover, medication is not effective for refractory (or intractable) epilepsy. The Electroencephalogram (EEG) recorded with scalp electrodes is generally used to screen and monitor epilepsy and to detect the epileptic focus. However, seizure activities occurring within deeper brain structures are often not recorded by EEG. Thus, the intracranial electrodes are used to detect seizures in deeper brain regions. Recording of electrocorticography (ECoG) signals from cortical surface and local field potentials (LFPs) from a brain depth help to localize the seizure onset region and track the seizure progression. This thesis describes the design and development of electrode arrays for recording brain signals intracranially to study convulsant and AED's effects on brain activities. EEG is a widely utilized electrophysiological monitoring technique to record the electrical activities of the brain for both research and clinical applications. Recently, the popularity of ECoG, compared to EEG, has increased due to relatively higher spatial resolution and improved signal-to-noise ratio (SNR). ECoG signals, the intracranial recording of electrical signatures of the brain, are recorded by minimally invasive planar electrode arrays placed on the cortical surface. Flexible arrays minimize the tissue damage and induce minimal inflammation upon implantation. However, the commercially available implantable electrode arrays offer a poor spatial resolution (electrodes with ~4 mm with a pitch of 10 mm). Therefore, there is a need for an electrode array with a higher density of electrodes to provide better spatial resolution for mapping the brain surface. We have developed a biocompatible, flexible, and high-density microelectrode array (MEA) for a simultaneous 32-channel recording of ECoG signals. In acute experiments, we have demonstrated that the fabricated MEA can record the baseline ECoG signals (amplitude ±100 µV range), the induced epileptic activities (amplitude ±1500 µV range), and the recovered baseline activities (amplitude ±50 µV range) after administering anti-epileptic drug from the cortical surface of an anesthetized rat (n=3 subjects). A significant increment in amplitude (approximately ten times baseline) of the ECoG signals was observed as the epilepsy was induced by topical application of a convulsant (bicuculline). After intraperitoneal application of an antiepileptic drug (phenytoin sodium), the recovered baseline signals with a lower amplitude than the normal baseline signals were observed. The power spectral density was determined to observe the frequency components present (up to 60 Hz) in the signal. The spatial distribution of the signals was studied for onset zone localization. Similarly, the design, fabrication, and characterization of a flexible biodegradable electrode array were described. The chronic in vivo experiments exhibited the capability of recording ECoG signals from the somatosensory cortex of rats (n=2 subjects). The PCBs were designed and fabricated for interfacing the array with OpenBCI Cyton Boards, used as the signal acquisition system. The epileptic activities were induced by peripheral electrical stimulation to the left forepaw of the rats and the induced epileptic activities were suppressed by administering an antiepileptic drug. The activities exhibited a significant variation in three neurological conditions: (i) Baseline (amplitude: ±30 µV), (ii) induced epileptic activities (amplitude ±200 µV range), and (iii) recovered baseline (amplitude ±10 µV range). The presence of frequency components in the recorded signals was studied by power spectral density (up to 100 Hz), which shows a significant change in the presence of low-frequency components (in the 1 Hz – 30 Hz range) during the induced epileptic activities. Though the ECoG signals can achieve better spatial resolution than EEG, it offers a limited understanding of the activities at a brain depth where the signal originates. Recently, the implanted depth electrodes have been used for acquiring signals (LFPs) from deeper regions of the brain to study the cortex, hippocampus, thalamus, and other deep brain structures. Our other work reports the design and fabrication of a silicon-based 13-channel single-shank microneedle electrode array to acquire and understand LFPs from a rat’s brain. In acute in vivo experiments, LFPs from the somatosensory cortex of anesthetized rats (n=3 subjects) were recorded and were acquired using OpenBCI Cyton Daisy Biosensing Board at normal, epileptic (chemically induced), and recovered (after application of anti-epileptic drug) conditions. The LFPs exhibited a significant variation in three neurological conditions: (i) Baseline LFP (amplitude ±25 µV range), (ii) epileptic activities (amplitude ±250 µV range), and (iii) recovered baseline (amplitude ±25 µV range). The presence of frequency components in the recorded signals was studied by power spectral density (up to 60 Hz), which shows a significant change in the presence of low-frequency components (up to 30 Hz) during induced epilepsy. The recorded signals helped us understand the response of the brain to convulsant and AED across the depth. We envisage these models may help to evaluate and understand the efficacy of AEDs using rats as an animal model. The results can establish that the OpenBCI Cyton Daisy Biosensing Boards can be used as a signal acquisition system for in vivo recording of rat brain signals, which was not widely used or reported.