Sanitta Thongpang

Graphene-based carbon-layered electrode array technology for neural imaging and optogenetic applications

Neural micro-electrode arrays that are transparent over a broad wavelength spectrum from ultraviolet to infrared could allow for simultaneous electrophysiology and optical imaging, as well as optogenetic modulation of the underlying brain tissue. The long-term biocompatibility and reliability of neural micro-electrodes also require their mechanical flexibility and compliance with soft tissues. Here we present a graphene-based, carbon-layered electrode array (CLEAR) device, which can be implanted on the brain surface in rodents for high-resolution neurophysiological recording. We characterize optical transparency of the device at >90% transmission over the ultraviolet to infrared spectrum and demonstrate its utility through optical interface experiments that use this broad spectrum transparency. These include optogenetic activation of focal cortical areas directly beneath electrodes, in vivo imaging of the cortical vasculature via fluorescence microscopy and 3D optical coherence tomography. This study demonstrates an array of interfacing abilities of the CLEAR device and its utility for neural applications.

A Micro-Electrocorticography Platform and Deployment Strategies for Chronic BCI Applications

Over the past decade, electrocorticography (ECoG) has been used for a wide set of clinical and experimental applications. Recently, there have been efforts in the clinic to adapt traditional ECoG arrays to include smaller recording contacts and spacing. These devices, which may be collectively called “micro-ECoG” arrays, are loosely defined as intercranial devices that record brain electrical activity on the submillimeter scale. An extensible 3D-platform of thin film flexible microscale ECoG arrays appropriate for Brain-Computer Interface (BCI) application, as well as monitoring epileptic activity, is presented. The designs utilize flexible film electrodes to keep the array in place without applying significant pressure to the brain and to enable radial subcranial deployment of multiple electrodes from a single craniotomy. Deployment techniques were tested in non-human primates, and stimulus-evoked activity and spontaneous epileptic activity were recorded. Further tests in BCI and epilepsy applications will make the electrode platform ready for initial human testing.

Differentiating closed-loop cortical intention from rest: building an asynchronous electrocorticographic BCI

OBJECTIVE Recent experiments have shown that electrocorticography (ECoG) can provide robust control signals for a brain-computer interface (BCI). Strategies that attempt to adapt a BCI control algorithm by learning from past trials often assume that the subject is attending to each training trial. Likewise, automatic disabling of movement control would be desirable during resting periods when random brain fluctuations might cause unintended movements of a device. To this end, our goal was to identify ECoG differences that arise between periods of active BCI use and rest. APPROACH We examined spectral differences in multi-channel, epidural micro-ECoG signals recorded from non-human primates when rest periods were interleaved between blocks of an active BCI control task. MAIN RESULTS Post-hoc analyses demonstrated that these states can be decoded accurately on both a trial-by-trial and real-time basis, and this discriminability remains robust over a period of weeks. In addition, high gamma frequencies showed greater modulation with desired movement direction, while lower frequency components demonstrated greater amplitude differences between task and rest periods, suggesting possible specialized BCI roles for these frequencies. SIGNIFICANCE The results presented here provide valuable insight into the neurophysiology of BCI control as well as important considerations toward the design of an asynchronous BCI system.

Optogenetic micro-electrocorticography for modulating and localizing cerebral cortex activity

OBJECTIVE Spatial localization of neural activity from within the brain with electrocorticography (ECoG) and electroencephalography remains a challenge in clinical and research settings, and while microfabricated ECoG (micro-ECoG) array technology continues to improve, complementary methods to simultaneously modulate cortical activity while recording are needed. APPROACH We developed a neural interface utilizing optogenetics, cranial windowing, and micro-ECoG arrays fabricated on a transparent polymer. This approach enabled us to directly modulate neural activity at known locations around micro-ECoG arrays in mice expressing Channelrhodopsin-2. We applied photostimuli varying in time, space and frequency to the cortical surface, and we targeted multiple depths within the cortex using an optical fiber while recording micro-ECoG signals. MAIN RESULTS Negative potentials of up to 1.5 mV were evoked by photostimuli applied to the entire cortical window, while focally applied photostimuli evoked spatially localized micro-ECoG potentials. Two simultaneously applied focal stimuli could be separated, depending on the distance between them. Photostimuli applied within the cortex with an optical fiber evoked more complex micro-ECoG potentials with multiple positive and negative peaks whose relative amplitudes depended on the depth of the fiber. SIGNIFICANCE Optogenetic ECoG has potential applications in the study of epilepsy, cortical dynamics, and neuroprostheses.

A cranial window imaging method for monitoring vascular growth around chronically implanted micro-ECoG devices.

Implantable neural micro-electrode arrays have the potential to restore lost sensory or motor function to many different areas of the body. However, the invasiveness of these implants often results in scar tissue formation, which can have detrimental effects on recorded signal quality and longevity. Traditional histological techniques can be employed to study the tissue reaction to implanted micro-electrode arrays, but these techniques require removal of the brain from the skull, often causing damage to the meninges and cortical surface. This is especially unfavorable when studying the tissue response to electrode arrays such as the micro-electrocorticography (micro-ECoG) device, which sits on the surface of the cerebral cortex. In order to better understand the biological changes occurring around these types of devices, a cranial window implantation scheme has been developed, through which the tissue response can be studied in vivo over the entire implantation period. Rats were implanted with epidural micro-ECoG arrays, over which glass coverslips were placed and sealed to the skull, creating cranial windows. Vascular growth around the devices was monitored for one month after implantation. It was found that blood vessels grew through holes in the micro-ECoG substrate, spreading over the top of the device. Micro-hematomas were observed at varying time points after device implantation in every animal, and tissue growth between the micro-ECoG array and the window occurred in several cases. Use of the cranial window imaging technique with these devices enabled the observation of tissue changes that would normally go unnoticed with a standard device implantation scheme.

Fabrication and utility of a transparent graphene neural electrode array for electrophysiology, in vivo imaging, and optogenetics

Transparent graphene-based neural electrode arrays provide unique opportunities for simultaneous investigation of electrophysiology, various neural imaging modalities, and optogenetics. Graphene electrodes have previously demonstrated greater broad-wavelength transmittance (∼90%) than other transparent materials such as indium tin oxide (∼80%) and ultrathin metals (∼60%). This protocol describes how to fabricate and implant a graphene-based microelectrocorticography (μECoG) electrode array and subsequently use this alongside electrophysiology, fluorescence microscopy, optical coherence tomography (OCT), and optogenetics. Further applications, such as transparent penetrating electrode arrays, multi-electrode electroretinography, and electromyography, are also viable with this technology. The procedures described herein, from the material characterization methods to the optogenetic experiments, can be completed within 3–4 weeks by an experienced graduate student. These protocols should help to expand the boundaries of neurophysiological experimentation, enabling analytical methods that were previously unachievable using opaque metal–based electrode arrays.

The effect of micro-ECoG substrate footprint on the meningeal tissue response

OBJECTIVE There is great interest in designing implantable neural electrode arrays that maximize function while minimizing tissue effects and damage. Although it has been shown that substrate geometry plays a key role in the tissue response to intracortically implanted, penetrating neural interfaces, there has been minimal investigation into the effect of substrate footprint on the tissue response to surface electrode arrays. This study investigates the effect of micro-electrocorticography (micro-ECoG) device geometry on the longitudinal tissue response. APPROACH The meningeal tissue response to two micro-ECoG devices with differing geometries was evaluated. The first device had each electrode site and trace individually insulated, with open regions in between, while the second device had a solid substrate, in which all 16 electrode sites were embedded in a continuous insulating sheet. These devices were implanted bilaterally in rats, beneath cranial windows, through which the meningeal tissue response was monitored for one month after implantation. Electrode site impedance spectra were also monitored during the implantation period. MAIN RESULTS It was observed that collagenous scar tissue formed around both types of devices. However, the distribution of the tissue growth was different between the two array designs. The mesh devices experienced thick tissue growth between the device and the cranial window, and minimal tissue growth between the device and the brain, while the solid device showed the opposite effect, with thick tissue forming between the brain and the electrode sites. SIGNIFICANCE These data suggest that an open architecture device would be more ideal for neural recording applications, in which a low impedance path from the brain to the electrode sites is critical for maximum recording quality.

Evaluation of micro-electrocorticographic electrodes for electrostimulation

Chronic neural recording and stimulation on the surface of the cortex with macroelectrodes has been shown to be promising for treating a wide range of neurological deficits. To enhance the specificity of these devices, dense arrangements of small area electrodes have been microfabricated for precise recording and control of neural populations. In this study micro-electrocorticographic (µECoG) electrodes were evaluated for electrostimulation. Surface modification with electrodeposited iridium oxide (EIrOx) resulted in lower impedance, higher charge carrying capacity, and lower, more linear voltage excursions during current controlled stimulation.

Flexible thin film electrode arrays for minimally-invasive neurological monitoring

We present approaches for using thin film polymeric electrode arrays for use in applications of minimally invasive neurological monitoring. The flexibility and unique surface properties of the thin-film polyimide substrate in combination with a compact device platform make them amenable to a variety of surgical implantation procedures. Using a rapid-prototyping and fabrication technique, arrays of various geometries can be fabricated within a week. In this paper we test two different approaches for deploying electrode arrays through small cranial openings.

Estimating cortical column sensory networks in rodents from micro-electrocorticograph (μECoG) recordings

&NA; Micro‐electrocorticograph (&mgr;ECoG) arrays offer the flexibility to record local field potentials (LFPs) from the surface of the cortex, using high density electrodes that are sub‐mm in diameter. Research to date has not provided conclusive evidence for the underlying signal generation of &mgr;ECoG recorded LFPs, or if &mgr;ECoG arrays can capture network activity from the cortex. We studied the pervading view of the LFP signal by exploring the spatial scale at which the LFP can be considered elemental. We investigated the underlying signal generation and ability to capture functional networks by implanting, &mgr;ECoG arrays to record sensory‐evoked potentials in four rats. The organization of the sensory cortex was studied by analyzing the sensory‐evoked potentials with two distinct modeling techniques: (1) The volume conduction model, that models the electrode LFPs with an electrostatic representation, generated by a single cortical generator, and (2) the dynamic causal model (DCM), that models the electrode LFPs with a network model, whose activity is generated by multiple interacting cortical sources. The volume conduction approach modeled activity from electrodes separated < 1000 &mgr;m, with reasonable accuracy but a network model like DCM was required to accurately capture activity > 1500 &mgr;m. The extrinsic network component in DCM was determined to be essential for accurate modeling of observed potentials. These results all point to the presence of a sensory network, and that &mgr;ECoG arrays are able to capture network activity in the neocortex. The estimated DCM network models the functional organization of the cortex, as signal generators for the &mgr;ECoG recorded LFPs, and provides hypothesis‐testing tools to explore the brain. HighlightsDCM accurately describes the potentials at all electrodes, while the volume conduction model is limited to activity located <1000 &mgr;m.DCM‐shotgun is a versatile initialization strategy to find a set of initial parameters that result in obtaining a high‐fidelity DCM solution.&mgr;ECoG arrays can capture and characterize neocortex network, demonstrated on the rodent sensory cortex.The estimated sensory network illustrates the local organization of the cortex and provides signal generators for the &mgr;ECoG recorded LFPs.