Shape-changing electrode array for minimally invasive large-scale intracranial brain activity mapping.

Large-scale brain activity mapping is important for understanding the neural basis of behaviour. Electrocorticograms (ECoGs) have high spatiotemporal resolution, bandwidth, and signal quality. However, the invasiveness and surgical risks of electrode array implantation limit its application scope. We developed an ultrathin, flexible shape-changing electrode array (SCEA) for large-scale ECoG mapping with minimal invasiveness. SCEAs were inserted into cortical surfaces in compressed states through small openings in the skull or dura and fully expanded to cover large cortical areas. MRI and histological studies on rats proved the minimal invasiveness of the implantation process and the high chronic biocompatibility of the SCEAs. High-quality micro-ECoG activities mapped with SCEAs from male rodent brains during seizures and canine brains during the emergence period revealed the spatiotemporal organization of different brain states with resolution and bandwidth that cannot be achieved using existing noninvasive techniques. The biocompatibility and ability to map large-scale physiological and pathological cortical activities with high spatiotemporal resolution, bandwidth, and signal quality in a minimally invasive manner offer SCEAs as a superior tool for applications ranging from fundamental brain research to brain-machine interfaces.

Instantaneous antidepressant effect of lateral habenula deep brain stimulation in rats studied with functional MRI.

The available treatments for depression have substantial limitations, including low response rates and substantial lag time before a response is achieved. We applied deep brain stimulation (DBS) to the lateral habenula (LHb) of two rat models of depression (Wistar Kyoto rats and lipopolysaccharide-treated rats) and observed an immediate (within seconds to minutes) alleviation of depressive-like symptoms with a high-response rate. Simultaneous functional MRI (fMRI) conducted on the same sets of depressive rats used in behavioral tests revealed DBS-induced activation of multiple regions in afferent and efferent circuitry of the LHb. The activation levels of brain regions connected to the medial LHb (M-LHb) were correlated with the extent of behavioral improvements. Rats with more medial stimulation sites in the LHb exhibited greater antidepressant effects than those with more lateral stimulation sites. These results indicated that the antidromic activation of the limbic system and orthodromic activation of the monoaminergic systems connected to the M-LHb played a critical role in the rapid antidepressant effects of LHb-DBS. This study indicates that M-LHb-DBS might act as a valuable, rapid-acting antidepressant therapeutic strategy for treatment-resistant depression and demonstrates the potential of using fMRI activation of specific brain regions as biomarkers to predict and evaluate antidepressant efficacy.

Enhanced Hemocompatibility of a Direct Chemical Vapor Deposition-Derived Graphene Film.

A wide range of biomedical devices are being used to treat cardiovascular diseases, and thus they routinely come into contact with blood. Insufficient hemocompatibility has been found to impair the functionality and safety of these devices through the activation of blood coagulation and the immune system. Numerous attempts have been made to develop surface modification approaches of the cardiovascular devices to improve their hemocompatibility. However, there are still no ideal "blood-friendly" coating materials, which possess the desired hemocompatibility, tissue compatibility, and mechanical properties. As a novel multifunctional material, graphene has been proposed for a wide range of biomedical applications. The chemical inertness, atomic smoothness, and high durability make graphene an ideal candidate as a surface coating material for implantable devices. Here, we evaluated the hemocompatibility of a graphene film prepared on quartz glasses (Gra-glasses) from a direct chemical vapor deposition process. We found that the graphene coating, which is free of transfer-mediating polymer contamination, significantly suppressed platelet adhesion and activation, prolonged coagulation time, and reduced ex vivo thrombosis formation. We attribute the excellent antithrombogenic properties of the Gra-glasses to the low surface roughness, low surface energy (especially the low polar component of the surface energy), and the negative surface charge of the graphene film. Given these excellent hemocompatible properties, along with its chemical inertness, high durability, and molecular impermeability, a graphene film holds great promise as an antithrombogenic coating for next-generation cardiovascular devices.

Carbon-Based Fiber Materials as Implantable Depth Neural Electrodes.

Implantable brain electrophysiology electrodes are valuable tools in both fundamental and applied neuroscience due to their ability to record neural activity with high spatiotemporal resolution from shallow and deep brain regions. Their use has been hindered, however, by the challenges in achieving chronically stable operations. Furthermore, implantable depth neural electrodes can only carry out limited data sampling within predefined anatomical regions, making it challenging to perform large-area brain mapping. Minimizing inflammatory responses and associated gliosis formation, and improving the durability and stability of the electrode insulation layers are critical to achieve long-term stable neural recording and stimulation. Combining electrophysiological measurements with simultaneous whole-brain imaging techniques, such as magnetic resonance imaging (MRI), provides a useful solution to alleviate the challenge in scalability of implantable depth electrodes. In recent years, various carbon-based materials have been used to fabricate flexible neural depth electrodes with reduced inflammatory responses and MRI-compatible electrodes, which allows structural and functional MRI mapping of the whole brain without obstructing any brain regions around the electrodes. Here, we conducted a systematic comparative evaluation on the electrochemical properties, mechanical properties, and MRI compatibility of different kinds of carbon-based fiber materials, including carbon nanotube fibers, graphene fibers, and carbon fibers. We also developed a strategy to improve the stability of the electrode insulation without sacrificing the flexibility of the implantable depth electrodes by sandwiching an inorganic barrier layer inside the polymer insulation film. These studies provide us with important insights into choosing the most suitable materials for next-generation implantable depth electrodes with unique capabilities for applications in both fundamental and translational neuroscience research.

Massive Growth of Graphene Quartz Fiber as a Multifunctional Electrode.

Quartz fiber, a widely used reinforcer with high tensile strength and excellent heat resistance, can have more attractive electrical applications such as electromagnetic interference shielding, static dissipation, and strain sensing if it becomes conductive. Many attempts have been made to increase the electrical conductivity of quartz fiber by surface coating of conductive polymers or plating of metal films, but suffers from sacrificing flexibility and causing heavy metal pollution. Here we designed and massively produced a hybrid structure of graphene quartz fiber (GQF) by a forced-flow chemical vapor deposition (CVD) method, which combines the excellent conductivity of graphene and the extraordinary properties of quartz fiber. The as-fabricated flexible GQF exhibited high sensitivity, fast response (<0.5 s) and good durability (∼5000 cycles) to organic solvent vapor, suitable as a real-time biomimetic gas sensor. Furthermore, the massively produced GQFs can be knitted into meter-scale fabrics with tunable conductivity (sheet resistances of 0.2-10 kΩ/sq) and superior electrothermal conversion efficiency (up to 980 °C within a few seconds at 24 V), thus propelling its promising application in industrial electric heaters. We expect this hybrid GQF material will greatly expand the applications of traditional quartz fiber into an infusive multifunctional regime.

Full activation pattern mapping by simultaneous deep brain stimulation and fMRI with graphene fiber electrodes.

Simultaneous deep brain stimulation (DBS) and functional magnetic resonance imaging (fMRI) constitutes a powerful tool for elucidating brain functional connectivity, and exploring neuromodulatory mechanisms of DBS therapies. Previous DBS-fMRI studies could not provide full activation pattern maps due to poor MRI compatibility of the DBS electrodes, which caused obstruction of large brain areas on MRI scans. Here, we fabricate graphene fiber (GF) electrodes with high charge-injection-capacity and little-to-no MRI artifact at 9.4T. DBS-fMRI with GF electrodes at the subthalamic nucleus (STN) in Parkinsonian rats reveal robust blood-oxygenation-level-dependent responses along the basal ganglia-thalamocortical network in a frequency-dependent manner, with responses from some regions not previously detectable. This full map indicates that STN-DBS modulates both motor and non-motor pathways, possibly through orthodromic and antidromic signal propagation. With the capability for full, unbiased activation pattern mapping, DBS-fMRI using GF electrodes can provide important insights into DBS therapeutic mechanisms in various neurological disorders.

Gas-Permeable, Irritation-Free, Transparent Hydrogel Contact Lens Devices with Metal-Coated Nanofiber Mesh for Eye Interfacing.

An electronic "smart" contact lens device with high gas permeability and optical transparency, as well as mechanical compliance and robustness, offers daily wear capability in eye interfacing and can have broad applications ranging from ocular diagnosis to augmented reality. Most existing contact lens electronics utilize gas-impermeable substrates, electronic components, and interfacial adhesion layers, which impedes them from applications requiring continuous daily wear. Here we report on the design and fabrication of an eye interfacing device with a commercial ocular contact lens as the substrate, metal-coated nanofiber mesh as the conductor, and in situ electrochemically deposited poly(3,4-ethylenedioxythiophene) (PEDOT) /poly(styrene sulfonate) (PSS) as the adhesion material. This hydrogel contact lens device shows high gas permeability, wettability, and level of hydration, in addition to excellent optical transparency, mechanical compliance, and robustness. Using a rabbit model, we found that the animals wearing these hydrogel contact lens devices continuously for 12 hours showed a level of corneal fluorescein staining comparable to those wearing pure hydrogel contact lenses for same period of time, with no obvious corneal abrasion or irritation, indicating their high level of safety for continuous daily wear. Finally, full-field electroretinogram (ERG) recordings on rabbits were carried out to demonstrate the functionality of this device. We believe that the strategy of integrating nanofiber mesh-based electronic components demonstrated here can offer a general platform for hydrogel electronics with the advantages of preserving the physiological and mechanical properties of the hydrogel, thus enabling seamless integration with biological tissues and providing various wearable or implantable sensors with improved biocompatibility for health monitoring or medical treatment.