Flexible, high-resolution cortical arrays with large coverage capture microscale high-frequency oscillations in patients with epilepsy.

OBJECTIVE: Effective surgical treatment of drug-resistant epilepsy depends on accurate localization of the epileptogenic zone (EZ). High-frequency oscillations (HFOs) are potential biomarkers of the EZ. Previous research has shown that HFOs often occur within submillimeter areas of brain tissue and that the coarse spatial sampling of clinical intracranial electrode arrays may limit the accurate capture of HFO activity. In this study, we sought to characterize microscale HFO activity captured on thin, flexible microelectrocorticographic (µECoG) arrays, which provide high spatial resolution over large cortical surface areas. METHODS: We used novel liquid crystal polymer thin-film µECoG arrays (.76-1.72-mm intercontact spacing) to capture HFOs in eight intraoperative recordings from seven patients with epilepsy. We identified ripple (80-250 Hz) and fast ripple (250-600 Hz) HFOs using a common energy thresholding detection algorithm along with two stages of artifact rejection. We visualized microscale subregions of HFO activity using spatial maps of HFO rate, signal-to-noise ratio, and mean peak frequency. We quantified the spatial extent of HFO events by measuring covariance between detected HFOs and surrounding activity. We also compared HFO detection rates on microcontacts to simulated macrocontacts by spatially averaging data. RESULTS: We found visually delineable subregions of elevated HFO activity within each µECoG recording. Forty-seven percent of HFOs occurred on single 200-µm-diameter recording contacts, with minimal high-frequency activity on surrounding contacts. Other HFO events occurred across multiple contacts simultaneously, with covarying activity most often limited to a .95-mm radius. Through spatial averaging, we estimated that macrocontacts with 2-3-mm diameter would only capture 44% of the HFOs detected in our µECoG recordings. SIGNIFICANCE: These results demonstrate that thin-film microcontact surface arrays with both highresolution and large coverage accurately capture microscale HFO activity and may improve the utility of HFOs to localize the EZ for treatment of drug-resistant epilepsy.

A novel micro-ECoG recording method for recording multisensory neural activity from the parietal to temporal cortices in mice.

Characterization of inter-regional interactions in brain is essential for understanding the mechanism relevant to normal brain function and neurological disease. The recently developed flexible micro (µ)-electrocorticography (µECoG) device is one prominent method used to examine large-scale cortical activity across multiple regions. The sheet-shaped µECoG electrodes arrays can be placed on a relatively wide area of cortical surface beneath the skull by inserting the device into the space between skull and brain. Although rats and mice are useful tools for neuroscience, current µECoG recording methods in these animals are limited to the parietal region of cerebral cortex. Recording cortical activity from the temporal region of cortex in mice has proven difficult because of surgical barriers created by the skull and surrounding temporalis muscle anatomy. Here, we developed a sheet-shaped 64-channel µECoG device that allows access to the mouse temporal cortex, and we determined the factor determining the appropriate bending stiffness for the µECoG electrode array. We also established a surgical technique to implant the electrode arrays into the epidural space over a wide area of cerebral cortex covering from the barrel field to olfactory (piriform) cortex, which is the deepest region of the cerebral cortex. Using histology and computed tomography (CT) images, we confirmed that the tip of the µECoG device reached to the most ventral part of cerebral cortex without causing noticeable damage to the brain surface. Moreover, the device simultaneously recorded somatosensory and odor stimulus-evoked neural activity from dorsal and ventral parts of cerebral cortex in awake and anesthetized mice. These data indicate that our µECoG device and surgical techniques enable the recording of large-scale cortical activity from the parietal to temporal cortex in mice, including somatosensory and olfactory cortices. This system will provide more opportunities for the investigation of physiological functions from wider areas of the mouse cerebral cortex than those currently available with existing ECoG techniques.

Conformable neural interface based on off-stoichiometry thiol-ene-epoxy thermosets.

Off-stoichiometry thiol-ene-epoxy (OSTE+) thermosets show low permeability to gases and little absorption of dissolved molecules, allow direct low-temperature dry bonding without surface treatments, have a low Young's modulus, and can be manufactured via UV polymerisation. For these reasons, OSTE+ thermosets have recently gained attention for the rapid prototyping of microfluidic chips. Moreover, their compatibility with standard clean-room processes and outstanding mechanical properties make OSTE+ an excellent candidate as a novel material for neural implants. Here we exploit OSTE+ to manufacture a conformable multilayer micro-electrocorticography array with 16 platinum electrodes coated with platinum black. The mechanical properties allow conformability to curved surfaces such as the brain. The low permeability and strong adhesion between layers improve the stability of the device. Acute experiments in mice show the multimodal capacity of the array to record and stimulate the neural tissue by smoothly conforming to the mouse cortex. Devices are not cytotoxic, and immunohistochemistry stainings reveal only modest foreign body reaction after two and six weeks of chronic implantation. This work introduces OSTE+ as a promising material for implantable neural interfaces.

Sufficient sampling for kriging prediction of cortical potential in rat, monkey, and human µECoG.

Objective. Large channel count surface-based electrophysiology arrays (e.g. µECoG) are high-throughput neural interfaces with good chronic stability. Electrode spacing remains ad hoc due to redundancy and nonstationarity of field dynamics. Here, we establish a criterion for electrode spacing based on the expected accuracy of predicting unsampled field potential from sampled sites.Approach. We applied spatial covariance modeling and field prediction techniques based on geospatial kriging to quantify sufficient sampling for thousands of 500 ms µECoG snapshots in human, monkey, and rat. We calculated a probably approximately correct (PAC) spacing based on kriging that would be required to predict µECoG fields at≤10% error for most cases (95% of observations).Main results. Kriging theory accurately explained the competing effects of electrode density and noise on predicting field potential. Across five frequency bands from 4-7 to 75-300 Hz, PAC spacing was sub-millimeter for auditory cortex in anesthetized and awake rats, and posterior superior temporal gyrus in anesthetized human. At 75-300 Hz, sub-millimeter PAC spacing was required in all species and cortical areas.Significance. PAC spacing accounted for the effect of signal-to-noise on prediction quality and was sensitive to the full distribution of non-stationary covariance states. Our results show that µECoG arrays should sample at sub-millimeter resolution for applications in diverse cortical areas and for noise resilience.

Progress in the Field of Micro-Electrocorticography.

Since the 1940s electrocorticography (ECoG) devices and, more recently, in the last decade, micro-electrocorticography (µECoG) cortical electrode arrays were used for a wide set of experimental and clinical applications, such as epilepsy localization and brain⁻computer interface (BCI) technologies. Miniaturized implantable µECoG devices have the advantage of providing greater-density neural signal acquisition and stimulation capabilities in a minimally invasive fashion. An increased spatial resolution of the µECoG array will be useful for greater specificity diagnosis and treatment of neuronal diseases and the advancement of basic neuroscience and BCI research. In this review, recent achievements of ECoG and µECoG are discussed. The electrode configurations and varying material choices used to design µECoG arrays are discussed, including advantages and disadvantages of µECoG technology compared to electroencephalography (EEG), ECoG, and intracortical electrode arrays. Electrode materials that are the primary focus include platinum, iridium oxide, poly(3,4-ethylenedioxythiophene) (PEDOT), indium tin oxide (ITO), and graphene. We discuss the biological immune response to µECoG devices compared to other electrode array types, the role of µECoG in clinical pathology, and brain⁻computer interface technology. The information presented in this review will be helpful to understand the current status, organize available knowledge, and guide future clinical and research applications of µECoG technologies.

Multi-scale analysis of neural activity in humans: Implications for micro-scale electrocorticography.

OBJECTIVE: Electrocorticography grids have been used to study and diagnose neural pathophysiology for over 50 years, and recently have been used for various neural prosthetic applications. Here we provide evidence that micro-scale electrodes are better suited for studying cortical pathology and function, and for implementing neural prostheses. METHODS: This work compares dynamics in space, time, and frequency of cortical field potentials recorded by three types of electrodes: electrocorticographic (ECoG) electrodes, non-penetrating micro-ECoG (µECoG) electrodes that use microelectrodes and have tighter interelectrode spacing; and penetrating microelectrodes (MEA) that penetrate the cortex to record single- or multiunit activity (SUA or MUA) and local field potentials (LFP). RESULTS: While the finest spatial scales are found in LFPs recorded intracortically, we found that LFP recorded from µECoG electrodes demonstrate scales of linear similarity (i.e., correlation, coherence, and phase) closer to the intracortical electrodes than the clinical ECoG electrodes. CONCLUSIONS: We conclude that LFPs can be recorded intracortically and epicortically at finer scales than clinical ECoG electrodes are capable of capturing. SIGNIFICANCE: Recorded with appropriately scaled electrodes and grids, field potentials expose a more detailed representation of cortical network activity, enabling advanced analyses of cortical pathology and demanding applications such as brain-computer interfaces.

Assessment of neurovascular dynamics during transient ischemic attack by the novel integration of micro-electrocorticography electrode array with functional photoacoustic microscopy.

This study developed a novel system combining a 16-channel micro-electrocorticography (µECoG) electrode array and functional photoacoustic microscopy (fPAM) to examine changes in neurovascular functions following transient ischemic attack (TIA) in rats. To mimic the pathophysiology of TIA, a modified photothrombotic ischemic model was developed by using 3 min illumination of 5 mW continuous-wave (CW) green laser light focusing on a distal branch of the middle cerebral artery (MCA). Cerebral blood volume (CBV), hemoglobin oxygen saturation (SO2), somatosensory evoked potentials (SSEPs) and alpha-to-delta ratio (ADR) were measured pre- and post-ischemia over a focal cortical region (i.e., 1.5×1.5 mm(2)). Unexpectedly, the SO2, peak-to-peak amplitude (PPA) of SSEPs and ADR recovered and achieved levels greater than the baseline values at the 4th hour post-ischemia induction without any intervention, whereas the CBV value only partially recovered. In other words, transient ischemia led to increased neural activity when the relative CBV was reduced, which may further compromise neural integrity or lead to subsequent vascular disease. This novel µECoG-fPAM system complements currently available imaging techniques and represents a promising technology for studying neurovascular coupling in animal models.

Smaller, softer, lower-impedance electrodes for human neuroprosthesis: a pragmatic approach.

Finding the most appropriate technology for building electrodes to be used for long term implants in humans is a challenging issue. What are the most appropriate technologies? How could one achieve robustness, stability, compatibility, efficacy, and versatility, for both recording and stimulation? There are no easy answers to these questions as even the most fundamental and apparently obvious factors to be taken into account, such as the necessary mechanical, electrical and biological properties, and their interplay, are under debate. We present here our approach along three fundamental parallel pathways: we reduced electrode invasiveness and size without impairing signal-to-noise ratio, we increased electrode active surface area by depositing nanostructured materials, and we protected the brain from direct contact with the electrode without compromising performance. Altogether, these results converge toward high-resolution ECoG arrays that are soft and adaptable to cortical folds, and have been proven to provide high spatial and temporal resolution. This method provides a piece of work which, in our view, makes several steps ahead in bringing such novel devices into clinical settings, opening new avenues in diagnostics of brain diseases, and neuroprosthetic applications.

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.