Effect of electric field direction on neuronal activity: an ex-vivo study.

The effect of electrical stimulation on neurons depends on the spatiotemporal properties of the applied electric field as well as on the biophysical properties of the neural tissue, which includes geometric and electrical characteristics of the cells, and the neural circuit dynamics. In this work, we characterize the effect of electric field direction on neural response in cortical layers. This can, for instance, enable more efficient (e.g., with reduced currents) and/or more selective stimulation. We stimulated mice brain slices using a recently developed brain slice platform to study transcranial currents in an ex-vivo model, where electrodes are separated from the brain slice to inject electric fields at a distance. By rotating the electrode array with respect to the slice, we changed the direction of electric field with respect to the cortical column. Our results demonstrate that in somatosensory cortex, the maximum local field potential (LFP) response is attained when the electric field is oriented parallel to the cortical column. For the same field intensity, when the field is oriented perpendicular to the cortical column, the LFP response is absent. This confirms that electric field direction is an important quantity to determine the effect of neuronal stimulation.

Focused Epicranial Brain Stimulation by Spatial Sculpting of Pulsed Electric Fields Using High Density Electrode Arrays.

Transcranial electrical neuromodulation of the central nervous system is used as a non-invasive method to induce neural and behavioral responses, yet targeted non-invasive electrical stimulation of the brain with high spatial resolution remains elusive. This work demonstrates a focused, steerable, high-density epicranial current stimulation (HD-ECS) approach to evoke neural activity. Custom-designed high-density (HD) flexible surface electrode arrays are employed to apply high-resolution pulsed electric currents through skull to achieve localized stimulation of the intact mouse brain. The stimulation pattern is steered in real time without physical movement of the electrodes. Steerability and focality are validated at the behavioral, physiological, and cellular levels using motor evoked potentials (MEPs), intracortical recording, and c-fos immunostaining. Whisker movement is also demonstrated to further corroborate the selectivity and steerability. Safety characterization confirmed no significant tissue damage following repetitive stimulation. This method can be used to design novel therapeutics and implement next-generation brain interfaces.

Residual voltage as an ad-hoc indicator of electrode damage in biphasic electrical stimulation.

Objective.We derive and demonstrate how residual voltage (RV) from a biphasic electrical stimulation pulse can be used to recognize degradation at the electrode-tissue interface.Approach.Using a first order model of the electrode-tissue interface and a rectangular biphasic stimulation current waveform, we derive the equations for RV as well as RV growth over several stimulation pulses. To demonstrate the use of RV for damage detection, we simulate accelerated damage on sputtered iridium oxide film (SIROF) electrodes using potential cycling. RV measurements of the degraded electrodes are compared against standard characterization methods of cyclic voltammetry and electrochemical impedance spectroscopy.Main results.Our theoretical discussion illustrates how an intrinsic RV arises even from perfectly balanced biphasic pulses due to leakage via the charge-transfer resistance. Preliminary data inin-vivorat experiments follow the derived model of RV growth, thereby validating our hypothesis that RV is a characteristic of the electrode-tissue interface. RV can therefore be utilized for detecting damage at the electrode. Our experimental results for damage detection show that delamination of SIROF electrodes causes a reduction in charge storage capacity, which in turn reflects a measurable increase in RV.Significance.Chronically implanted electrical stimulation systems with multi-electrode arrays have been the focus of physiological engineering research for the last decade. Changes in RV over time can be a quick and effective method to identify and disconnect faulty electrodes in large arrays. Timely diagnoses of electrode status can ensure optimal long term operation, and prevent further damage to the tissue near these electrodes.

Hydrogel-based electrodes for selective cervical vagus nerve stimulation.

Objective.Electrical vagus nerve stimulation (VNS) has the potential to treat a wide variety of diseases by modulating afferent and efferent communication to the heart, lungs, esophagus, stomach, and intestines. Although distal vagal nerve branches, close to end organs, could provide a selective therapeutic approach, these locations are often surgically inaccessible. In contrast, the cervical vagus nerve has been targeted for decades using surgically implantable helix electrodes to treat epileptic seizures and depression; however, to date, clinical implementation of VNS has relied on an electrode with contacts that fully wrap around the nerve, producing non-selective activation of the entire nerve. Here we demonstrate selective cervical VNS using cuff electrodes with multiple contacts around the nerve circumference to target different functional pathways.Approach.These flexible probes were adjusted to the diameter of the nerve using an adhesive hydrogel wrap to create a robust electrode interface. Our approach was verified in a rat model by demonstrating that cervical VNS produces neural activity in the abdominal vagus nerve while limiting effects on the cardiovascular system (i.e. changes in heart rate or blood pressure).Main results.This study demonstrates the potential for selective cervical VNS as a therapeutic approach for modulating distal nerve branches while reducing off target effects.Significance.This methodology could potentially be refined to treat gastrointestinal, metabolic, inflammatory, cardiovascular, and respiratory diseases amenable to vagal neuromodulatory control.

Effect of skull thickness and conductivity on current propagation for noninvasively injected currents.

Objective.When currents are injected into the scalp, e.g. during transcranial current stimulation, the resulting currents generated in the brain are substantially affected by the changes in conductivity and geometry of intermediate tissue. In this work, we introduce the concept of 'skull-transparent' currents, for which the changing conductivity does not significantly alter the field while propagating through the head.Approach.We establish transfer functions relating scalp currents to head potentials in accepted simplified models of the head, and find approximations for which skull-transparency holds. The current fields resulting from specified current patterns are calculated in multiple head models, including MRI heads and compared with homogeneous heads to characterize the transparency. Experimental validation is performed by measuring the current field in head phantoms.Main results.The main theoretical result is derived from observing that at high spatial frequencies, in the transfer function relating currents injected into the scalp to potential generated inside the head, the conductivity terms form a multiplicative factor and do not otherwise influence the transfer function. This observation is utilized to design injected current waveforms that maintain nearly identical focusing patterns independently of the changes in skull conductivity and thickness for a wide range of conductivity and thickness values in an idealized spherical head model as well as in a realistic MRI-based head model. Experimental measurements of the current field in an agar-based head phantom confirm the transparency of these patterns.Significance.Our results suggest the possibility that well-chosen patterns of current injection result in precise focusing inside the brain even withouta prioriknowledge of exact conductivities of intermediate layers.

Parylene neural probe with embedded CMOS multiplexing amplifier.

We present a method for embedding integrated circuit chips in parylene neural probes where Anisotropic Conductive Film (ACF) electrically and physically connects the chip to the probe. Adequate insulation of the assembly is verified up to 150 h in vitro (testing ongoing). A custom-designed 8-to-1 multiplexing amplifier for neural application was fabricated in a 0.18 µm CMOS process. As a feasibility demonstration, the $830 \mu \mathrm {m}\times 1030 \mu \mathrm {m}$ die was connected to a parylene probe on a glass substrate. Preliminary results of the amplifier tests indicate similar performance in air and in phosphate buffered saline (PBS), and demonstrate around 200 V/V amplification of signals in saline.

Insulation of thin-film parylene-C/platinum probes in saline solution through encapsulation in multilayer ALD ceramic films.

The long-term electrical leakage performance of parylene-C/platinum/parylene-C (Px/Pt/Px) interconnect in saline is evaluated using electrochemical impedance spectroscopy (EIS). Three kinds of additional ceramic encapsulation layers between the metal and Px are characterized: 50 nm-thick alumina (Al2O3), 50 nm-thick titania (TiO2), and 80 nm-thick Al2O3-TiO2 nanolaminate (NL). The Al2O3 and TiO2 encapsulation layers worsen the overall insulation properties. The NL encapsulation layer improves the insulation when combined with a TiO2 outer layer to promote adhesion to the Px. Experiments are performed with various insulation promotion treatments: A-174 silane (A174) treatment before Px deposition (to promote adhesion); SF6 plasma treatment (F) after Px deposition (to increase hydrophobicity); and ion-milling descum (IM) after Px deposition (to prevent parylene oxidation). A174 and F treatments do not have a significant impact, while IM leads to worse insulation performance. A circuit model elucidates the insulation characteristics of Px-ceramic-Pt-ceramic-Px interconnect. These studies provide a foundation for processing ultra-compliant neural probes with long-term chronic utility.

In vitro electrochemical characterization of polydopamine melanin as a tissue stimulating electrode material.

The properties of redox active polydopamine melanin (PDM) films as a coating material for neural electrodes were evaluated. PDM films with nanometer-scale thicknesses exhibit dc bias dependent charge injection capacities (CIC) with maximum values of 110 ± 23 µC cm-2 at 0.2V (vs Ag/AgCl) and reduce the interfacial impedance compared to inorganic conducting films. PDM films exhibited an asymmetric impedance response to positive and negative dc biases with minimum interfacial impedance at 0.2V (vs Ag/AgCl). An explanation for the observed bias-dependent electrochemical behavior is presented.

A silicon neural probe fabricated using DRIE on bonded thin silicon.

A silicon neural probe fabricated using a deep reactive ion etching based process on 250 µm thin silicon wafers was developed. The fabricated probes replicate the design of soft parylene-C based probes embedded in dissolvable needles and can therefore also be used to test the encapsulation properties of parylene-C in-vivo without introducing additional effects introduced by the dissolvable gel. The process also demonstrates the possibility of performing conventional photolithography on substrates bonded to a handle wafer using a backgrinding liquid wax (BGL7080) as an adhesive. This technique would allow integration of Si wafer thinning into the fabrication of neural probes, potentially allowing a range of neural probes of different thicknesses to be fabricated. Fabricated probes were characterized using electrochemical impedance spectroscopy (EIS) yielding a measured impedance value of ~80 kΩ at 1 kHz for 15 µm by 115 µm platinum electrodes, indicating that extracellular neural recordings are possible. The neural probes were inserted into the substantia nigra of a mouse that showed successful recording of neural activity. Probes fabricated using this technique can thus be potentially used in the study of Parkinson's disease.