An electroencephalogram microdisplay to visualize neuronal activity on the brain surface.

Functional mapping during brain surgery is applied to define brain areas that control critical functions and cannot be removed. Currently, these procedures rely on verbal interactions between the neurosurgeon and electrophysiologist, which can be time-consuming. In addition, the electrode grids that are used to measure brain activity and to identify the boundaries of pathological versus functional brain regions have low resolution and limited conformity to the brain surface. Here, we present the development of an intracranial electroencephalogram (iEEG)-microdisplay that consists of freestanding arrays of 2048 GaN light-emitting diodes laminated on the back of micro-electrocorticography electrode grids. With a series of proof-of-concept experiments in rats and pigs, we demonstrate that these iEEG-microdisplays allowed us to perform real-time iEEG recordings and display cortical activities by spatially corresponding light patterns on the surface of the brain in the surgical field. Furthermore, iEEG-microdisplays allowed us to identify and display cortical landmarks and pathological activities from rat and pig models. Using a dual-color iEEG-microdisplay, we demonstrated coregistration of the functional cortical boundaries with one color and displayed the evolution of electrical potentials associated with epileptiform activity with another color. The iEEG-microdisplay holds promise to facilitate monitoring of pathological brain activity in clinical settings.

Intraoperative application and early experience with novel high-resolution, high-channel-count thin-film electrodes for human microelectrocorticography.

OBJECTIVE: The study objective was to evaluate intraoperative experience with newly developed high-spatial-resolution microelectrode grids composed of poly(3,4-ethylenedioxythiophene) with polystyrene sulfonate (PEDOT:PSS), and those composed of platinum nanorods (PtNRs). METHODS: A cohort of patients who underwent craniotomy for pathological tissue resection and who had high-spatial-resolution microelectrode grids placed intraoperatively were evaluated. Patient demographic and baseline clinical variables as well as relevant microelectrode grid characteristic data were collected. The primary and secondary outcome measures of interest were successful microelectrode grid utilization with usable resting-state or task-related data, and grid-related adverse intraoperative events and/or grid dysfunction. RESULTS: Included in the analysis were 89 cases of patients who underwent a craniotomy for resection of neoplasms (n = 58) or epileptogenic tissue (n = 31). These cases accounted for 94 grids: 58 PEDOT:PSS and 36 PtNR grids. Of these 94 grids, 86 were functional and used successfully to obtain cortical recordings from 82 patients. The mean cortical grid recording duration was 15.3 ± 1.15 minutes. Most recordings in patients were obtained during experimental tasks (n = 52, 58.4%), involving language and sensorimotor testing paradigms, or were obtained passively during resting state (n = 32, 36.0%). There were no intraoperative adverse events related to grid placement. However, there were instances of PtNR grid dysfunction (n = 8) related to damage incurred by suboptimal preoperative sterilization (n = 7) and improper handling (n = 1); intraoperative recordings were not performed. Vaporized peroxide sterilization was the most optimal sterilization method for PtNR grids, providing a significantly greater number of usable channels poststerilization than did steam-based sterilization techniques (median 905.0 [IQR 650.8-935.5] vs 356.0 [IQR 18.0-597.8], p = 0.0031). CONCLUSIONS: High-spatial-resolution microelectrode grids can be readily incorporated into appropriately selected craniotomy cases for clinical and research purposes. Grids are reliable when preoperative handling and sterilization considerations are accounted for. Future investigations should compare the diagnostic utility of these high-resolution grids to commercially available counterparts and assess whether diagnostic discrepancies relate to clinical outcomes.

The Brain Electroencephalogram Microdisplay for Precision Neurosurgery.

Brain surgeries are among the most delicate clinical procedures and must be performed with the most technologically robust and advanced tools. When such surgical procedures are performed in functionally critical regions of the brain, functional mapping is applied as a standard practice that involves direct coordinated interactions between the neurosurgeon and the clinical neurology electrophysiology team. However, information flow during these interactions is commonly verbal as well as time consuming which in turn increases the duration and cost of the surgery, possibly compromising the patient outcomes. Additionally, the grids that measure brain activity and identify the boundaries of pathological versus functional brain regions suffer from low resolution (3-10 mm contact to contact spacing) with limited conformity to the brain surface. Here, we introduce a brain intracranial electroencephalogram microdisplay (Brain-iEEG-microdisplay) which conforms to the brain to measure the brain activity and display changes in near real-time (40 Hz refresh rate) on the surface of the brain in the surgical field. We used scalable engineered gallium nitride (GaN) substrates with 6" diameter to fabricate, encapsulate, and release free-standing arrays of up to 2048 GaN light emitting diodes (µLEDs) in polyimide substrates. We then laminated the µLED arrays on the back of micro-electrocorticography (µECoG) platinum nanorod grids (PtNRGrids) and developed hardware and software to perform near real-time intracranial EEG analysis and activation of light patterns that correspond to specific cortical activities. Using the Brain-iEEG-microdisplay, we precisely ideFSntified and displayed important cortical landmarks and pharmacologically induced pathological activities. In the rat model, we identified and displayed individual cortical columns corresponding to individual whiskers and the near real-time evolution of epileptic discharges. In the pig animal model, we demonstrated near real-time mapping and display of cortical functional boundaries using somatosensory evoked potentials (SSEP) and display of responses to direct electrical stimulation (DES) from the surface or within the brain tissue. Using a dual-color Brain-iEEG-microdisplay, we demonstrated co-registration of the functional cortical boundaries with one color and displayed the evolution of electrical potentials associated with epileptiform activity with another color. The Brain-iEEG-microdisplay holds the promise of increasing the efficiency of diagnosis and possibly surgical treatment, thereby reducing the cost and improving patient outcomes which would mark a major advancement in neurosurgery. These advances can also be translated to broader applications in neuro-oncology and neurophysiology.

Constructing 2D maps of human spinal cord activity and isolating the functional midline with high-density microelectrode arrays.

Intraoperative neuromonitoring (IONM) is a widely used practice in spine surgery for early detection and minimization of neurological injury. IONM is most commonly conducted by indirectly recording motor and somatosensory evoked potentials from either muscles or the scalp, which requires large-amplitude electrical stimulation and provides limited spatiotemporal information. IONM may inform of inadvertent events during neurosurgery after they occur, but it does not guide safe surgical procedures when the anatomy of the diseased spinal cord is distorted. To overcome these limitations and to increase our understanding of human spinal cord neurophysiology, we applied a microelectrode array with hundreds of channels to the exposed spinal cord during surgery and resolved spatiotemporal dynamics with high definition. We used this method to construct two-dimensional maps of responsive channels and define with submillimeter precision the electrophysiological midline of the spinal cord. The high sensitivity of our microelectrode array allowed us to record both epidural and subdural responses at stimulation currents that are well below those used clinically and to resolve postoperative evoked potentials when IONM could not. Together, these advances highlight the potential of our microelectrode arrays to capture previously unexplored spinal cord neural activity and its spatiotemporal dynamics at high resolution, offering better electrophysiological markers that can transform IONM.

Human brain mapping with multithousand-channel PtNRGrids resolves spatiotemporal dynamics.

Electrophysiological devices are critical for mapping eloquent and diseased brain regions and for therapeutic neuromodulation in clinical settings and are extensively used for research in brain-machine interfaces. However, the existing clinical and experimental devices are often limited in either spatial resolution or cortical coverage. Here, we developed scalable manufacturing processes with a dense electrical connection scheme to achieve reconfigurable thin-film, multithousand-channel neurophysiological recording grids using platinum nanorods (PtNRGrids). With PtNRGrids, we have achieved a multithousand-channel array of small (30 µm) contacts with low impedance, providing high spatial and temporal resolution over a large cortical area. We demonstrated that PtNRGrids can resolve submillimeter functional organization of the barrel cortex in anesthetized rats that captured the tissue structure. In the clinical setting, PtNRGrids resolved fine, complex temporal dynamics from the cortical surface in an awake human patient performing grasping tasks. In addition, the PtNRGrids identified the spatial spread and dynamics of epileptic discharges in a patient undergoing epilepsy surgery at 1-mm spatial resolution, including activity induced by direct electrical stimulation. Collectively, these findings demonstrated the power of the PtNRGrids to transform clinical mapping and research with brain-machine interfaces.

Monolithic and Scalable Au Nanorod Substrates Improve PEDOT-Metal Adhesion and Stability in Neural Electrodes.

Poly(3,4-ethylenenedioxythiophene) or PEDOT is a promising candidate for next-generation neuronal electrode materials but its weak adhesion to underlying metallic conductors impedes its potential. An effective method of mechanically anchoring the PEDOT within an Au nanorod (Au-nr) structure is reported and it is demonstrated that it provides enhanced adhesion and overall PEDOT layer stability. Cyclic voltammetry (CV) stress is used to investigate adhesion and stability of spin-cast and electrodeposited PEDOT. The Au-nr adhesion layer permits 10 000 CV cycles of coated PEDOT film in phosphate buffered saline solution without delamination nor significant change of the electrochemical impedance, whereas PEDOT coating film on planar Au electrodes delaminates at or below 1000 cycles. Under CV stress, spin-cast PEDOT on planar Au delaminates, whereas electroplated PEDOT on planar Au encounters surface leaching/decomposition. After 5 weeks of accelerated aging tests at 60 °C, the electrodeposited PEDOT/Au-nr microelectrodes demonstrate a 92% channel survival compared to only 25% survival for spin-cast PEDOT on planar films. Furthermore, after a 10 week chronic implantation onto mouse barrel cortex, PEDOT/Au-nr microelectrodes do not exhibit delamination nor morphological changes, whereas the conventional PEDOT microelectrodes either partially or fully delaminate. Immunohistochemical evaluation demonstrates no or minimal response to the PEDOT implant.

Gold catalyzed nickel disilicide formation: a new solid-liquid-solid phase growth mechanism.

The vapor-liquid-solid (VLS) mechanism is the predominate growth mechanism for semiconductor nanowires (NWs). We report here a new solid-liquid-solid (SLS) growth mechanism of a silicide phase in Si NWs using in situ transmission electron microcopy (TEM). The new SLS mechanism is analogous to the VLS one in relying on a liquid-mediating growth seed, but it is fundamentally different in terms of nucleation and mass transport. In SLS growth of Ni disilicide, the Ni atoms are supplied from remote Ni particles by interstitial diffusion through a Si NW to the pre-existing Au-Si liquid alloy drop at the tip of the NW. Upon supersaturation of both Ni and Si in Au, an octahedral nucleus of Ni disilicide (NiSi2) forms at the center of the Au liquid alloy, which thereafter sweeps through the Si NW and transforms Si into NiSi2. The dissolution of Si by the Au alloy liquid mediating layer proceeds with contact angle oscillation at the triple point where Si, oxide of Si, and the Au alloy meet, whereas NiSi2 is grown from the liquid mediating layer in an atomic stepwise manner. By using in situ quenching experiments, we are able to measure the solubility of Ni and Si in the Au-Ni-Si ternary alloy. The Au-catalyzed mechanism can lower the formation temperature of NiSi2 by 100 °C compared with an all solid state reaction.

Nucleation and atomic layer reaction in nickel silicide for defect-engineered Si nanochannels.

At the nanoscale, defects can significantly impact phase transformation processes and change materials properties. The material nickel silicide has been the industry standard electrical contact of silicon microelectronics for decades and is a rich platform for scientific innovation at the conjunction of materials and electronics. Its formation in nanoscale silicon devices that employ high levels of strain, intentional, and unintentional twins or grain boundaries can be dramatically different from the commonly conceived bulk processes. Here, using in situ high-resolution transmission electron microscopy (HRTEM), we capture single events during heterogeneous nucleation and atomic layer reaction of nickel silicide at various crystalline boundaries in Si nanochannels for the first time. We show through systematic experiments and analytical modeling that unlike other typical face-centered cubic materials such as copper or silicon the twin defects in NiSi2 have high interfacial energies. We observe that these twin defects dramatically change the behavior of new phase nucleation and can have direct implications for ultrascaled devices that are prone to defects or may utilize them to improve device performance.

Ultrashort channel silicon nanowire transistors with nickel silicide source/drain contacts.

We demonstrate the shortest transistor channel length (17 nm) fabricated on a vapor-liquid-solid (VLS) grown silicon nanowire (NW) by a controlled reaction with Ni leads on an in situ transmission electron microscope (TEM) heating stage at a moderate temperature of 400 °C. NiSi(2) is the leading phase, and the silicide-silicon interface is an atomically sharp type-A interface. At such channel lengths, high maximum on-currents of 890 (µA/µm) and a maximum transconductance of 430 (µS/µm) were obtained, which pushes forward the performance of bottom-up Si NW Schottky barrier field-effect transistors (SB-FETs). Through accurate control over the silicidation reaction, we provide a systematic study of channel length dependent carrier transport in a large number of SB-FETs with channel lengths in the range of 17 nm to 3.6 µm. Our device results corroborate with our transport simulations and reveal a characteristic type of short channel effects in SB-FETs, both in on- and off-state, which is different from that in conventional MOSFETs, and that limits transport parameter extraction from SB-FETs using conventional field-effect transconductance measurements.