Ludwig KA, Miriani RM, Langhals NB, Joseph MD, Anderson DJ, Kipke DR. Using a common average reference to improve cortical neuron recordings from microelectrode arrays.

Biosensors interact with biological systems at the surface of the sensor. Coating these sensors with electrically active polymers has been suggested to improve this interface. The electrically conducting polymer poly (3, 4 ethylenedioxythiophene) (PEDOT) enhances electrical recordings by improving conductivity while maintaining chemical stability. It also offers great flexibility in studying cell substrate interactions because of the variety of counter-ions that can be incorporated into the PEDOT matrix. To provide any true benefit in cell culture or in vivo experiments, the cytotoxicity of PEDOT must first be determined. This study evaluated the cytotoxicity of PEDOT doped with either polystyrene sulfonate (PSS) or phosphate buffered saline (PBS) ions and tested the efficacy of using the conductive PEDOT substrates for myoblast proliferation and differentiation. Results show that PEDOT/PBS and PEDOT/PSS are not cytotoxic to cells and successfully support cellular proliferation and differentiation. These results establish PEDOT as a material for cell-substrate interface studies. With biosensors being modified using the new polymer coating PEDOT, this cytotoxicity study provides evidence that PEDOT coatings will not induce a cytotoxic response when implanted in vivo.

Delivering drugs directly to the brain tissue opens new approaches to disease treatment and improving neural interfaces. Several approaches using neural prostheses have been made to deliver drugs directly with bypassing the blood-brain barrier (BBB) [1, 2]. In this paper, we propose a new polymer-based flexible microelectrode with drug delivery capability. The probe was fabricated and tested for electrical and fluidic functionality in early stage design. In vivo chronic recording experiments succeeded in demonstrating the in vivo reliability of the probe. Successful in vivo experiments confirm the suitability of the probes as implantable chronic recording devices with robust fluid delivery function.

Brain-machine interface decoding algorithms need to be predicated on assumptions that are easily met outside of an experimental setting to enable a practical clinical device. Given present technology limitations, there is a need for decoding algorithms which a) are not dependent upon a large number of neurons for control, b) are adaptable to alternative sources of neuronal input such as local field potentials, and c) require only marginal training data for daily calibrations. Moreover, practical algorithms must recognize when the user is not intending to generate a control output and eliminate poor training data. In this study, we introduce and evaluate a Bayesian Maximum-Likelihood Estimation (bMLE) strategy to address the issues of isolating quality training data and self-paced control. Six animal subjects demonstrate that a multiple state classification task, loosely based on the standard center-out task, can be accomplished with fewer than five engaged neurons while requiring less than ten trials for algorithm training. In addition, untrained animals quickly obtained accurate device control utilizing local field potentials as well as neurons in cingulate cortex, two non-traditional neural inputs.

While the development of microelectrode arrays has enabled access to disparate regions of a cortex for neurorehabilitation, neuroprosthetic and basic neuroscience research, accurate interpretation of the signals and manipulation of the cortical neurons depend upon the anatomical placement of the electrode arrays in a layered cortex. Toward this end, this report compares two in vivo methods for identifying the placement of electrodes in a linear array spaced 100 µm apart based on in situ laminar analysis of (1) ketamine-xylazine-induced field potential oscillations in a rat motor cortex and (2) an intracortical electrical stimulation-induced movement threshold. The first method is based on finding the polarity reversal in laminar oscillations which is reported to appear at the transition between layers IV and V in laminar 'high voltage spindles' of the rat cortical column. Analysis of histological images in our dataset indicates that polarity reversal is detected 150.1 ± 104.2 µm below the start of layer V. The second method compares the intracortical microstimulation currents that elicit a physical movement for anodic versus cathodic stimulation. It is based on the hypothesis that neural elements perpendicular to the electrode surface are preferentially excited by anodic stimulation while cathodic stimulation excites those with a direction component parallel to its surface. With this method, we expect to see a change in the stimulation currents that elicits a movement at the beginning of layer V when comparing anodic versus cathodic stimulation as the upper cortical layers contain neuronal structures that are primarily parallel to the cortical surface and lower layers contain structures that are primarily perpendicular. Using this method, there was a 78.7 ± 68 µm offset in the estimate of the depth of the start of layer V. The polarity reversal method estimates the beginning of layer V within ±90 µm with 95% confidence and the intracortical stimulation method estimates it within ±69.3 µm. We propose that these methods can be used to estimate the in situ location of laminar electrodes implanted in the rat motor cortex.

The purpose of this study is to optimize poly(3,4,-ethylenedioxythiophene) (PEDOT) polymerization into decellular nerve scaffolding for interfacing to peripheral nerves. Our ultimate aim is to permanently implant highly conductive peripheral nerve interfaces between amputee, stump, nerve fascicles and prosthetic electronics. Decellular nerve (DN) scaffolds are an FDA approved biomaterial (Axogen ) with the flexible tensile properties needed for successful permanent coaptation to peripheral nerves. Biocompatible, electroconductive, PEDOT facilitates electrical conduction through PEDOT coated acellular muscle. New electrochemical methods were used to polymerize various PEDOT concentrations into DN scaffolds without the need for a final dehydration step. DN scaffolds were then tested for electrical impedance and charge density. PEDOT coated DN scaffold materials were also implanted as 15–20mm peripheral nerve grafts. Measurement of in-situ nerve conduction immediately followed grafting. DN showed significant improvements in impedance for dehydrated and hydrated, DN, polymerized with moderate and low PEDOT concentrations when they were compared with DN alone (a ≤ 0.05). These measurements were equivalent to those for DN with maximal PEDOT concentrations. In-situ, nerve conduction measurements demonstrated that DN alone is a poor electro-conductor while the addition of PEDOT allows DN scaffold grafts to compare favorably with the “gold standard”, autograft (Table 1). Surgical handling characteristics for conductive hydrated PEDOT DN scaffolds were rated 3 (pliable) while the dehydrated models were rated 1 (very stiff) when compared with autograft ratings of 4 (normal). Low concentrations of PEDOT on DN scaffolds provided significant increases in electro active properties which were comparable to the densest PEDOT coatings. DN pliability was closely maintained by continued hydration during PEDOT electrochemical polymerization without compromising electroconductivity.

Cortical recording devices hold promise for providing augmented control of neuroprostheses and brain-computer interfaces in patients with severe loss of motor function due to injury or disease. This paper reports on the preliminary in vitro and in vivo results of our microscale implantable neural interface (MINI) probe system. The MINI is designed to use proven components and materials with a modular structure to facilitate ongoing improvements as new technologies become available. This device takes advantage of existing, well-characterized Michigan probe technologies and combines them to form a multichannel, multiprobe cortical assembly. To date, rat, rabbit, and non-human primate models have been implanted to test surgical techniques and in vivo functionality of the MINI. Results demonstrate the ability to form a contained hydrostatic environment surrounding the implanted probes for extended periods and the ability of this device to record electrophysiological signals with high SNRs. This is the first step in the realization of a cortically-controlled neuroprosthesis designed for human applications.

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