Emma Maggiolini

Carbon nanotube composite coating of neural microelectrodes preferentially improves the multiunit signal-to-noise ratio

Extracellular metal microelectrodes are widely used to record single neuron activity in vivo. However, their signal-to-noise ratio (SNR) is often far from optimal due to their high impedance value. It has been recently reported that carbon nanotube (CNT) coatings may decrease microelectrode impedance, thus improving their performance. To tease out the different contributions to SNR of CNT-coated microelectrodes we carried out impedance and noise spectroscopy measurements of platinum/tungsten microelectrodes coated with a polypyrrole-CNT composite. Neuronal signals were recorded in vivo from rat cortex by employing tetrodes with two recording sites coated with polypyrrole-CNT and the remaining two left untreated. We found that polypyrrole-CNT coating significantly reduced the microelectrode impedance at all neuronal signal frequencies (from 1 to 10 000 Hz) and induced a significant improvement of the SNR, up to fourfold on average, in the 150-1500 Hz frequency range, largely corresponding to the multiunit frequency band. An equivalent circuit, previously proposed for porous conducting polymer coatings, reproduced the impedance spectra of our coated electrodes but could not explain the frequency dependence of SNR improvement following polypyrrole-CNT coating. This implies that neither the neural signal amplitude, as recorded by a CNT-coated metal microelectrode, nor noise can be fully described by the equivalent circuit model we used here and suggests that a more detailed approach may be needed to better understand the signal propagation at the electrode-solution interface. Finally, the presence of significant noise components that are neither thermal nor electronic makes it difficult to establish a direct relationship between the actual electrode noise and the impedance spectra.

New perspectives on the dialogue between brains and machines

Brain-machine interfaces (BMIs) are mostly investigated as a means to provide paralyzed people with new communication channels with the external world. However, the communication between brain and artificial devices also offers a unique opportunity to study the dynamical properties of neural systems. This review focuses on bidirectional interfaces, which operate in two ways by translating neural signals into input commands for the device and the output of the device into neural stimuli. We discuss how bidirectional BMIs help investigating neural information processing and how neural dynamics may participate in the control of external devices. In this respect, a bidirectional BMI can be regarded as a fancy combination of neural recording and stimulation apparatus, connected via an artificial body. The artificial body can be designed in virtually infinite ways in order to observe different aspects of neural dynamics and to approximate desired control policies.

Superior Electrochemical Performance of Carbon Nanotubes Directly Grown on Sharp Microelectrodes

We report for the first time how coatings made by directly growing carbon nanotubes (CNTs) on the tip of neural microelectrodes outperform others made by electrodeposited CNT composites. Not only do they reduce microelectrode impedance but they also are able to inject high currents without degradation and are stable in time. These results suggest that they are excellent candidates for chronic applications especially when both neural recording and stimulation have to be performed by the same microelectrode.

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.

Biologically compatible neural interface to safely couple nanocoated electrodes to the surface of the brain.

The ongoing interest in densely packed miniaturized electrode arrays for high-resolution epicortical recordings has induced many researchers to explore the use of nanomaterial coatings to reduce electrode impedance while increasing signal-to-noise ratio and charge injection capability. Although these materials are very effective, their use in clinical practice is strongly inhibited by concerns about the potential risks derived from the use of nanomaterials in direct contact with the human brain. In this work we propose a novel approach to safely couple nanocoated electrodes to the brain surface by encapsulating them with a biocompatible hydrogel. We prove that fibrin hydrogel coating over nanocoated high-density arrays of epicortical microelectrodes is electrically transparent and allows avoiding direct exposure of the brain tissue to the nanocoatings while maintaining all the advantages derived from the nanostructured electrode surface. This method may make available acute and sub-acute neural recordings with nanocoated high-resolution arrays for clinical applications.

Highly Stable Glassy Carbon Interfaces for Long-Term Neural Stimulation and Low-Noise Recording of Brain Activity

We report on the superior electrochemical properties, in-vivo performance and long term stability under electrical stimulation of a new electrode material fabricated from lithographically patterned glassy carbon. For a direct comparison with conventional metal electrodes, similar ultra-flexible, micro-electrocorticography (μ-ECoG) arrays with platinum (Pt) or glassy carbon (GC) electrodes were manufactured. The GC microelectrodes have more than 70% wider electrochemical window and 70% higher CTC (charge transfer capacity) than Pt microelectrodes of similar geometry. Moreover, we demonstrate that the GC microelectrodes can withstand at least 5 million pulses at 0.45 mC/cm2 charge density with less than 7.5% impedance change, while the Pt microelectrodes delaminated after 1 million pulses. Additionally, poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS) was selectively electrodeposited on both sets of devices to specifically reduce their impedances for smaller diameters (<60 μm). We observed that PEDOT-PSS adhered significantly better to GC than Pt, and allowed drastic reduction of electrode size while maintaining same amount of delivered current. The electrode arrays biocompatibility was demonstrated through in-vitro cell viability experiments, while acute in vivo characterization was performed in rats and showed that GC microelectrode arrays recorded somatosensory evoked potentials (SEP) with an almost twice SNR (signal-to-noise ratio) when compared to the Pt ones.

PEDOT-CNT-Coated Low-Impedance, Ultra-Flexible, and Brain-Conformable Micro-ECoG Arrays

Electrocorticography (ECoG) is becoming a common tool for clinical applications, such as preparing patients for epilepsy surgery or localizing tumor boundaries, as it successfully balances invasiveness and information quality. Clinical ECoG arrays use millimeter-scale electrodes and centimeter-scale pitch and cannot precisely map neural activity. Higher-resolution electrodes are of interest for both current clinical applications, providing access to more precise neural activity localization and novel applications, such as neural prosthetics, where current information density and spatial resolution is insufficient to suitably decode signals for a chronic brain-machine interface. Developing such electrodes is not trivial because their small contact area increases the electrode impedance, which seriously affects the signal-to-noise ratio, and adhering such an electrode to the brain surface becomes critical. The most straightforward approach requires increasing the array conformability with flexible substrates while improving the electrode performance using materials with superior electrochemical properties. In this paper, we propose an ultra-flexible and conformable polyimide-based micro-ECoG array of submillimeter recording sites electrochemically coated with high surface area conductive polymer-carbon nanotube composites to improve their brain-electrical coupling capabilities. We characterized our devices both electrochemically and by recording from rat somatosensory cortex in vivo. The performance of the coated and uncoated electrodes was directly compared by simultaneously recording the same neuronal activity during multiwhisker deflection stimulation. Finally, we assessed the effect of electrode size on the extraction of somatosensory evoked potentials and found that in contrast to the normal high-impedance microelectrodes, the recording capabilities of our low-impedance microelectrodes improved upon reducing their size from 0.2 to 0.1 mm.

Bio-inspired hybrid microelectrodes: a hybrid solution to improve long-term performance of chronic intracortical implants

The use of implants that allow chronic electrical stimulation and recording in the brain of human patients is currently limited by a series of events that cause the deterioration over time of both the electrode surface and the surrounding tissue. The main reason of failure is the tissue inflammatory reaction that eventually causes neuronal loss and glial encapsulation, resulting in a progressive increase of the electrode-electrolyte impedance. Here, we describe a new method to create bio-inspired electrodes to mimic the mechanical properties and biological composition of the host tissue. This combination has a great potential to increase the implant lifetime by reducing tissue reaction and improving electrical coupling. Our method implies coating the electrode with reprogrammed neural or glial cells encapsulated within a hydrogel layer. We chose fibrin as a hydrogel and primary hippocampal neurons or astrocytes from rat brain as cellular layer. We demonstrate that fibrin coating is highly biocompatible, forms uniform coatings of controllable thickness, does not alter the electrochemical properties of the microelectrode and allows good quality recordings. Moreover, it reduces the amount of host reactive astrocytes – over time – compared to a bare wire and is fully reabsorbed by the surrounding tissue within 7 days after implantation, avoiding the common problem of hydrogels swelling. Both astrocytes and neurons could be successfully grown onto the electrode surface within the fibrin hydrogel without altering the electrochemical properties of the microelectrode. This bio-hybrid device has therefore a good potential to improve the electrical integration at the neuron-electrode interface and support the long-term success of neural prostheses.

Shaping the Dynamics of a Bidirectional Neural Interface

Progress in decoding neural signals has enabled the development of interfaces that translate cortical brain activities into commands for operating robotic arms and other devices. The electrical stimulation of sensory areas provides a means to create artificial sensory information about the state of a device. Taken together, neural activity recording and microstimulation techniques allow us to embed a portion of the central nervous system within a closed-loop system, whose behavior emerges from the combined dynamical properties of its neural and artificial components. In this study we asked if it is possible to concurrently regulate this bidirectional brain-machine interaction so as to shape a desired dynamical behavior of the combined system. To this end, we followed a well-known biological pathway. In vertebrates, the communications between brain and limb mechanics are mediated by the spinal cord, which combines brain instructions with sensory information and organizes coordinated patterns of muscle forces driving the limbs along dynamically stable trajectories. We report the creation and testing of the first neural interface that emulates this sensory-motor interaction. The interface organizes a bidirectional communication between sensory and motor areas of the brain of anaesthetized rats and an external dynamical object with programmable properties. The system includes (a) a motor interface decoding signals from a motor cortical area, and (b) a sensory interface encoding the state of the external object into electrical stimuli to a somatosensory area. The interactions between brain activities and the state of the external object generate a family of trajectories converging upon a selected equilibrium point from arbitrary starting locations. Thus, the bidirectional interface establishes the possibility to specify not only a particular movement trajectory but an entire family of motions, which includes the prescribed reactions to unexpected perturbations.

Suppression of activity in the forelimb motor cortex temporarily enlarges forelimb representation in the homotopic cortex in adult rats.

After forelimb motor cortex (FMC) damage, the unaffected homotopic motor cortex showed plastic changes. The present experiments were designed to clarify the electrophysiological nature of these interhemispheric effects. To this end, the output reorganization of the FMC was investigated after homotopic area activity was suppressed in adult rats. FMC output was compared after lidocaine‐induced inactivation (L‐group) or quinolinic acid‐induced lesion (Q‐group) of the contralateral homotopic cortex. In the Q‐group of animals, FMC mapping was performed, respectively, 3 days (Q3D group) and 2 weeks (Q2W group) after cortical lesion. In each animal, FMC output was assessed by mapping movements induced by intracortical microstimulation (ICMS) in both hemispheres (hemisphere ipsilateral and contralateral to injections). The findings demonstrated that in the L‐group, the size of forelimb representation was 42.2% higher than in the control group (P < 0.0001). The percentage of dual forelimb–vibrissa movement sites significantly increased over the controls (P < 0.0005). The dual‐movement sites occupied a strip of the map along the rostrocaudal border between the forelimb and vibrissa representations. This form of interhemispheric diaschisis had completely reversed, with the recovery of the baseline map, 3 days after the lesion in the contralateral FMC. This restored forelimb map showed no ICMS‐induced changes 2 weeks after the lesion in the contralateral FMC. The present results suggest that the FMCs in the two hemispheres interact continuously through predominantly inhibitory influences that preserve the forelimb representation and the border vs. vibrissa representation.