Intan Technologies integrated circuits can produce analog-to-digital conversion artifacts that affect neural signal acquisition.

OBJECTIVE: Intan Technologies' integrated circuits (ICs) are valuable tools for neurophysiological data acquisition, providing signal amplification, filtering, and digitization from many channels (up to 64 channels / chip) at high sampling rates (up to 30 kSPS) within a compact package (≤ 9x7 mm). However, we found that the analog-to-digital converters (ADCs) in the Intan RHD2000 series ICs can produce artifacts in recorded signals. Here, we examine the effects of these ADC artifacts on neural signal quality and describe a method to detect them in recorded data. Approach: We identified two types of ADC artifacts produced by Intan ICs: 1) jumps, resulting from missing output codes, and 2) flatlines, resulting from overrepresented output codes. We identified ADC artifacts in neural recordings acquired with Intan RHD2000 ICs and tested the repeated performance of 17 ICs in vitro. With the on-chip digital-signal-processing disabled, we detected the ADC artifacts in each test recording by examining the distribution of unfiltered ADC output codes. Main Results: We found larger ADC artifacts in recordings using the Intan RHX data acquisition software versions 3.0-3.2, which did not run the necessary ADC calibration command when the inputs to the Intan recording controller were rescanned. This has been corrected in the Intan RHX software version 3.3. We found that the ADC calibration routine significantly reduced, but did not fully eliminate, the occurrence and size of ADC artifacts as compared with recordings acquired when the calibration routine was not run (p < 0.0001). When the ADC calibration routine was run, we found that the artifacts produced by each ADC were consistent over time, enabling us to sort ICs by performance. Significance: Our findings call attention to the importance of evaluating signal quality when acquiring electrophysiological data using Intan Technologies ICs and offer a method for detecting ADC artifacts in recorded data. .

High-resolution neural recordings improve the accuracy of speech decoding.

Patients suffering from debilitating neurodegenerative diseases often lose the ability to communicate, detrimentally affecting their quality of life. One solution to restore communication is to decode signals directly from the brain to enable neural speech prostheses. However, decoding has been limited by coarse neural recordings which inadequately capture the rich spatio-temporal structure of human brain signals. To resolve this limitation, we performed high-resolution, micro-electrocorticographic (µECoG) neural recordings during intra-operative speech production. We obtained neural signals with 57× higher spatial resolution and 48% higher signal-to-noise ratio compared to macro-ECoG and SEEG. This increased signal quality improved decoding by 35% compared to standard intracranial signals. Accurate decoding was dependent on the high-spatial resolution of the neural interface. Non-linear decoding models designed to utilize enhanced spatio-temporal neural information produced better results than linear techniques. We show that high-density µECoG can enable high-quality speech decoding for future neural speech prostheses.

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.

Flexural bending to approximate cortical forces exerted by electrocorticography (ECoG) arrays.

Objective.The force that an electrocorticography (ECoG) array exerts on the brain manifests when it bends to match the curvature of the skull and cerebral cortex. This force can negatively impact both short-term and long-term patient outcomes. Here we provide a mechanical characterization of a novel liquid crystal polymer (LCP) ECoG array prototype to demonstrate that its thinner geometry reduces the force potentially applied to the cortex of the brain.Approach.We built a low-force flexural testing machine to measure ECoG array bending forces, calculate their effective flexural moduli, and approximate the maximum force they could exerted on the human brain.Main results.The LCP ECoG prototype was found to have a maximal force less than 20% that of any commercially available ECoG arrays that were tested. However, as a material, LCP was measured to be as much as 24× more rigid than silicone, which is traditionally used in ECoG arrays. This suggests that the lower maximal force resulted from the prototype's thinner profile (2.9×-3.25×).Significance.While decreasing material stiffness can lower the force an ECoG array exhibits, our LCP ECoG array prototype demonstrated that flexible circuit manufacturing techniques can also lower these forces by decreasing ECoG array thickness. Flexural tests of ECoG arrays are necessary to accurately assess these forces, as material properties for polymers and laminates are often scale dependent. As the polymers used are anisotropic, elastic modulus cannot be used to predict ECoG flexural behavior. Accounting for these factors, we used our four-point flexure testing procedure to quantify the forces exerted on the brain by ECoG array bending. With this experimental method, ECoG arrays can be designed to minimize force exerted on the brain, potentially improving both acute and chronic clinical utility.

Intraoperative microseizure detection using a high-density micro-electrocorticography electrode array.

One-third of epilepsy patients suffer from medication-resistant seizures. While surgery to remove epileptogenic tissue helps some patients, 30-70% of patients continue to experience seizures following resection. Surgical outcomes may be improved with more accurate localization of epileptogenic tissue. We have previously developed novel thin-film, subdural electrode arrays with hundreds of microelectrodes over a 100-1000 mm2 area to enable high-resolution mapping of neural activity. Here, we used these high-density arrays to study microscale properties of human epileptiform activity. We performed intraoperative micro-electrocorticographic recordings in nine patients with epilepsy. In addition, we recorded from four patients with movement disorders undergoing deep brain stimulator implantation as non-epileptic controls. A board-certified epileptologist identified microseizures, which resembled electrographic seizures normally observed with clinical macroelectrodes. Recordings in epileptic patients had a significantly higher microseizure rate (2.01 events/min) than recordings in non-epileptic subjects (0.01 events/min; permutation test, P = 0.0068). Using spatial averaging to simulate recordings from larger electrode contacts, we found that the number of detected microseizures decreased rapidly with increasing contact diameter and decreasing contact density. In cases in which microseizures were spatially distributed across multiple channels, the approximate onset region was identified. Our results suggest that micro-electrocorticographic electrode arrays with a high density of contacts and large coverage are essential for capturing microseizures in epilepsy patients and may be beneficial for localizing epileptogenic tissue to plan surgery or target brain stimulation.

Flexible, high-resolution thin-film electrodes for human and animal neural research.

Objective.Brain functions such as perception, motor control, learning, and memory arise from the coordinated activity of neuronal assemblies distributed across multiple brain regions. While major progress has been made in understanding the function of individual neurons, circuit interactions remain poorly understood. A fundamental obstacle to deciphering circuit interactions is the limited availability of research tools to observe and manipulate the activity of large, distributed neuronal populations in humans. Here we describe the development, validation, and dissemination of flexible, high-resolution, thin-film (TF) electrodes for recording neural activity in animals and humans.Approach.We leveraged standard flexible printed-circuit manufacturing processes to build high-resolution TF electrode arrays. We used biocompatible materials to form the substrate (liquid crystal polymer; LCP), metals (Au, PtIr, and Pd), molding (medical-grade silicone), and 3D-printed housing (nylon). We designed a custom, miniaturized, digitizing headstage to reduce the number of cables required to connect to the acquisition system and reduce the distance between the electrodes and the amplifiers. A custom mechanical system enabled the electrodes and headstages to be pre-assembled prior to sterilization, minimizing the setup time required in the operating room. PtIr electrode coatings lowered impedance and enabled stimulation. High-volume, commercial manufacturing enables cost-effective production of LCP-TF electrodes in large quantities.Main Results. Our LCP-TF arrays achieve 25× higher electrode density, 20× higher channel count, and 11× reduced stiffness than conventional clinical electrodes. We validated our LCP-TF electrodes in multiple human intraoperative recording sessions and have disseminated this technology to >10 research groups. Using these arrays, we have observed high-frequency neural activity with sub-millimeter resolution.Significance.Our LCP-TF electrodes will advance human neuroscience research and improve clinical care by enabling broad access to transformative, high-resolution electrode arrays.

A simple and robust approach to reducing contact resistance in organic transistors.

Efficient injection of charge carriers from the contacts into the semiconductor layer is crucial for achieving high-performance organic devices. The potential drop necessary to accomplish this process yields a resistance associated with the contacts, namely the contact resistance. A large contact resistance can limit the operation of devices and even lead to inaccuracies in the extraction of the device parameters. Here, we demonstrate a simple and efficient strategy for reducing the contact resistance in organic thin-film transistors by more than an order of magnitude by creating high work function domains at the surface of the injecting electrodes to promote channels of enhanced injection. We find that the method is effective for both organic small molecule and polymer semiconductors, where we achieved a contact resistance as low as 200 Ωcm and device charge carrier mobilities as high as 20 cm2V-1s-1, independent of the applied gate voltage.

Balancing Charge Storage and Mobility in an Oligo(Ether) Functionalized Dioxythiophene Copolymer for Organic- and Aqueous- Based Electrochemical Devices and Transistors.

This work presents a soluble oligo(ether)-functionalized propylenedioxythiophene (ProDOT)-based copolymer as a versatile platform for a range of high-performance electrochemical devices, including organic electrochemical transistors (OECTs), electrochromic displays, and energy-storage devices. This polymer exhibits dual electroactivity in both aqueous and organic electrolyte systems, redox stability for thousands of redox cycles, and charge-storage capacity exceeding 80 F g-1 . As an electrochrome, this material undergoes full colored-to-colorless optical transitions on rapid time scales (<2 s) and impressive electrochromic contrast (Δ%T > 70%). Incorporation of the polymer into OECTs yields accumulation-mode devices with an ION/OFF current ratio of 105 , high transconductance without post-treatments, as well as competitive hole mobility and volumetric capacitance, making it an attractive candidate for biosensing applications. In addition to being the first ProDOT-based OECT active material reported to date, this is also the first reported OECT material synthesized via direct(hetero)arylation polymerization, which is a highly favorable polymerization method when compared to commonly used Stille cross-coupling. This work provides a demonstration of how a single ProDOT-based polymer, prepared using benign polymerization chemistry and functionalized with highly polar side chains, can be used to access a range of highly desirable properties and performance metrics relevant to electrochemical, optical, and bioelectronic applications.

The Role of the Side Chain on the Performance of N-type Conjugated Polymers in Aqueous Electrolytes.

We report a design strategy that allows the preparation of solution processable n-type materials from low boiling point solvents for organic electrochemical transistors (OECTs). The polymer backbone is based on NDI-T2 copolymers where a branched alkyl side chain is gradually exchanged for a linear ethylene glycol-based side chain. A series of random copolymers was prepared with glycol side chain percentages of 0, 10, 25, 50, 75, 90, and 100 with respect to the alkyl side chains. These were characterized to study the influence of the polar side chains on interaction with aqueous electrolytes, their electrochemical redox reactions, and performance in OECTs when operated in aqueous electrolytes. We observed that glycol side chain percentages of >50% are required to achieve volumetric charging, while lower glycol chain percentages show a mixed operation with high required voltages to allow for bulk charging of the organic semiconductor. A strong dependence of the electron mobility on the fraction of glycol chains was found for copolymers based on NDI-T2, with a significant drop as alkyl side chains are replaced by glycol side chains.

Fluorinated benzalkylsilane molecular rectifiers.

We report on the synthesis and electrical properties of nine new alkylated silane self-assembled monolayers (SAMs) - (EtO)3Si(CH2)nN = CHPhX where n = 3 or 11 and X = 4-CF3, 3,5-CF3, 3-F-4-CF3, 4-F, or 2,3,4,5,6-F, and explore their rectification behavior in relation to their molecular structure. The electrical properties of the films were examined in a metal/insulator/metal configuration, with a highly-doped silicon bottom contact and a eutectic gallium-indium liquid metal (EGaIn) top contact. The junctions exhibit high yields (>90%), a remarkable resistance to bias stress, and current rectification ratios (R) between 20 and 200 depending on the structure, degree of order, and internal dipole of each molecule. We found that the rectification ratio correlates positively with the strength of the molecular dipole moment and it is reduced with increasing molecular length.

Survey of western Canadian veterinary practices: A demographic profile.

A mixed-mode survey was used to describe the demographics of the veterinary profession in western Canada and to assess the demand for veterinary practitioners. Data were received from 655 practices (response rate = 52%), providing demographic data on 1636 individual practitioners. Most (60%) respondents self-classified their practices as exclusively small animal, while 25% and 4% were mixed animal or exclusively food animal practices, respectively. Across all practices, 77% of practitioners' time was devoted to small animals and the average mixed animal practice devoted 60% of practitioners' time to small animals. After accounting for practices that did not respond, there were ~300 full-time equivalent (FTE) vacant positions for veterinary associates; however, only 12% of practices were in urgent need of hiring an associate veterinarian. This report informs both prospective employees and employers on the state of the marketplace for veterinary associates, and provides an overview of the demographics of the veterinary profession in western Canada.

Enquête auprès des pratiques vétérinaires de l'Ouest canadien : un profil démographique. Une enquête de type mixte a été utilisée pour décrire les données démographiques de la profession vétérinaire dans l'Ouest canadien et évaluer la demande de praticiens vétérinaires. Des données ont été reçues de 655 pratiques (taux de réponse = 52 %) et ont fourni des données démographiques sur 1636 praticiens individuels. La majorité (60 %) des répondants ont classé leur pratique comme traitant exclusivement des petits animaux, tandis que 25 % et 4 % étaient des pratiques mixtes ou exclusivement pour animaux destinés à l'alimentation. Dans toutes les pratiques, 77 % du temps des praticiens était consacré aux petits animaux et la pratique mixte moyenne consacrait 60 % du temps des praticiens aux petits animaux. Après avoir tenu compte des pratiques qui n'ont pas répondu, il y avait ~300 postes équivalent temps plein (ETP) vacants pour les vétérinaires salariés. Cependant, seulement 12 % des pratiques éprouvaient un besoin urgent d'embaucher un vétérinaire salarié. Ce rapport informe les employés et les employeurs éventuels sur l'état du marché pour les vétérinaires salariés et présente un aperçu des données démographiques de la profession vétérinaire dans l'Ouest canadien.(Traduit par Isabelle Vallières).