Hirohito Sawahata

Intrasulcal electrocorticography in macaque monkeys with minimally invasive neurosurgical protocols.

Electrocorticography (ECoG), multichannel brain-surface recording and stimulation with probe electrode arrays, has become a potent methodology not only for clinical neurosurgery but also for basic neuroscience using animal models. The highly evolved primates brain has deep cerebral sulci, and both gyral and intrasulcal cortical regions have been implicated in important functional processes. However, direct experimental access is typically limited to gyral regions, since placing probes into sulci is difficult without damaging the surrounding tissues. Here we describe a novel methodology for intrasulcal ECoG in macaque monkeys. We designed and fabricated ultra-thin flexible probes for macaques with micro-electro-mechanical systems technology. We developed minimally invasive operative protocols to implant the probes by introducing cutting-edge devices for human neurosurgery. To evaluate the feasibility of intrasulcal ECoG, we conducted electrophysiological recording and stimulation experiments. First, we inserted parts of the Parylene-C-based probe into the superior temporal sulcus to compare visually evoked ECoG responses from the ventral bank of the sulcus with those from the surface of the inferior temporal cortex. Analyses of power spectral density and signal-to-noise ratio revealed that the quality of the ECoG signal was comparable inside and outside of the sulcus. Histological examination revealed no obvious physical damage in the implanted areas. Second, we placed a modified silicone ECoG probe into the central sulcus and also on the surface of the precentral gyrus for stimulation. Thresholds for muscle twitching were significantly lower during intrasulcal stimulation compared to gyral stimulation. These results demonstrate the feasibility of intrasulcal ECoG in macaques. The novel methodology proposed here opens up a new frontier in neuroscience research, enabling the direct measurement and manipulation of electrical activity in the whole brain.

Characteristics of temporal fluctuation of the vertical ground reaction force during quiet stance in Parkinson's disease

Stance instability is seen in late stage Parkinsons disease (PD). Stabilometer-based center-of-pressure (COP) evaluation is an easy, routine method for measuring postural control ability. Most of the stabilometer- and force plate-based studies on upright postural control have discussed horizontal COP component control. Previous studies on vertical component control have been few, and no fractal analysis-based study on the component has been reported. We aimed to show the influence of neurological changes and aging on the vertical component and the difference in fluctuation pattern behavior in healthy young and elderly subjects as well as Parkinsonian patients. Detrended fluctuation analysis was used to study characteristics of fluctuation of vertical ground reaction force. In the three groups, all scaling exponents (α, α1, α2), which are time-correlated data of vertical ground reaction force, had a value >0 and <0.5 (0<α<0.5). Additionally, α and α2 were significantly different between PD and the other groups. Significant differences were observed between PD and the other groups regarding RMS, maximum peak value, and coefficient of variance. We demonstrated statistically significant differences in vertical ground reaction force between Parkinsonian patients and the other groups, suggesting that a neurological influence with PD may be markedly reflected in the vertical ground reaction force.

Nanoscale‐Tipped High‐Aspect‐Ratio Vertical Microneedle Electrodes for Intracellular Recordings

Intracellular recording nanoscale electrode devices provide the advantages of a high spatial resolution and high sensitivity. However, the length of nanowire/nanotube-based nanoelectrodes is currently limited to <10 μm long due to fabrication issues for high-aspect-ratio nanoelectrodes. The concept reported here can address the technological limitations by fabricating >100 μm long nanoscale-tipped electrodes, which show intracellular recording capability.

Associative-memory representations emerge as shared spatial patterns of theta activity spanning the primate temporal cortex

Highly localized neuronal spikes in primate temporal cortex can encode associative memory; however, whether memory formation involves area-wide reorganization of ensemble activity, which often accompanies rhythmicity, or just local microcircuit-level plasticity, remains elusive. Using high-density electrocorticography, we capture local-field potentials spanning the monkey temporal lobes, and show that the visual pair-association (PA) memory is encoded in spatial patterns of theta activity in areas TE, 36, and, partially, in the parahippocampal cortex, but not in the entorhinal cortex. The theta patterns elicited by learned paired associates are distinct between pairs, but similar within pairs. This pattern similarity, emerging through novel PA learning, allows a machine-learning decoder trained on theta patterns elicited by a particular visual item to correctly predict the identity of those elicited by its paired associate. Our results suggest that the formation and sharing of widespread cortical theta patterns via learning-induced reorganization are involved in the mechanisms of associative memory representation.

Dissolvable Base Scaffolds Allow Tissue Penetration of High-Aspect-Ratio Flexible Microneedles

Microscale needle technology is important in electrophysiological studies, drug/chemical delivery systems, optogenetic applications, and so on. In this study, dissolvable needle-base scaffold realizes penetration of high-aspect-ratio flexible microneedles (e.g., <5 μm diameter and >500 μm length) into biological tissues. This methodology, which is applicable to numerous high-aspect-ratio flexible microneedles, should reduce the invasiveness and provide safer tissue penetrations than conventional approaches.

Super multi-channel recording systems with UWB wireless transmitter for BMI

In order to realize a low-invasive and high accuracy Brain-Machine Interface (BMI) system for clinical applications, a super multi-channel recording system was developed in which 4096 channels of Electrocorticogram (ECoG) signal can be amplified and transmitted to outside the body by using an Ultra Wide Band (UWB) wireless system. Also, a high density, flexible electrode array made by using a Parylene-C substrate was developed that is composed of units of 32-ch recording arrays. We have succeeded in an evaluation test of UWB wireless transmitting using a body phantom system.

Micro-electrode arrays for multi-channel motor unit EMG recording

We report an array of micro-electrodes, which can record multi-channel motor unit (MU) electromyogram (EMG) signals with a high spatial resolution. As a basic structure of the electrode, we fabricated an array of 200-μm-square Si-pyramids with the height of 200 μm by Tetramethylammonium hydroxide (TMAH), in order for robust MU-EMG recordings without conductive gel. Platinum (Pt) was used as the electrode material and parylene-C was used as the insulator for the Pt-electrode. The fabricated μEMG electrode array, which was connected to a recording system, clearly detected MU-EMG action potentials from a human forearm. In addition, different MU-EMG signals between the μEMG electrodes were detected by crooking the fingers. These results indicate that the μEMG array device becomes a powerful tool for medical applications including myoelectric prosthetic technologies.

Reflectance imaging by fiber bundle endoscope: Vertical reconstruction by multipositional illumination

Fiber bundles for imaging internal organs with minimum physical damage have been increasingly developed for both basic life sciences and clinical applications. Reflectance imaging is possible using fiber bundles for detecting the intrinsic optical contrast of blood vessels and tissue structure. The placement of an illumination source adjacent to imaging optics causes scattered light from deeper tissue layers to illuminate superficial tissues and results in a reflectance image. However, it does not have focal capacity and lacks depth resolution. In this study, we performed spatial analysis for the vertical reconstruction of in vivo tissues using a multipositional illumination scheme. The observed image corresponded to the “shadow” of a target object. When we manipulated the location of illumination, the shadow moved horizontally depending on the depth of the target. We used this horizontal displacement as a cue and successfully performed the vertical reconstruction of mouse brain blood vessels.

Single 5 μm diameter needle electrode block modules for unit recordings in vivo

Investigations into mechanisms in various cortical areas can be greatly improved and supported by stable recording of single neuronal activity. In this study, fine silicon wire electrodes (diameter 3 μm, length 160 μm) are fabricated by vapor–liquid–solid (VLS) growth with the aim of stabilizing recording and reducing the invasiveness on the measurement procedure. The electrode is fabricated on a modular 1 ×  1 mm2 conductive silicon block that can be assembled into a number of different device packages, for example on rigid or flexible printed circuit boards (PCB). After plating with a 5 μm diameter platinum black, the needle exhibits an electrical impedance of ~100 kΩ at 1 kHz in saline. The in vivo recording capability of the device is demonstrated using mice, and spike signals with peak-to-peak amplitudes of 200−300 μV in the range 0.5−3 kHz are stably detected, including single-unit activities in cortical layer 2/3. In addition, the device packaged with a flexible PCB shows stable unit recordings for 98.5 min (n = 4). Consequently, our modular, low-invasive needle electrode block devices present an effective route for single-unit recordings in vivo, as well as demonstrating adaptability in device design for a diverse range of experiments.

Vertically aligned extracellular microprobe arrays/(111) integrated with (100)-silicon mosfet amplifiers

We report a heterogeneous integration of vertically aligned extracellular micro-scale silicon (Si)-probe arrays/(111) with MOSFET amplifiers/(100), by IC processes and subsequent vapor-liquid-solid (VLS) growth of Si-probes. To improve the extracellular recording capability of the microprobe with a high impedance of > 1 MΩ at 1 kHz, here we integrated (100)-Si source follower buffer amplifiers by ~700°C VLS growth compatible (100)-Si MOSFET technology. Without on-chip source follower, output/input signal ratio of the microprobe in saline was 0.59, which was improved to 0.72 by the on-chip source follower configuration, while the signal-to-noise ratio (SNR) was improved to 12.5 dB in the frequency of extracellular recording. These results indicate that the integration of the source follower buffer amplifiers becomes a powerful way to enhance the performance of high impedance microprobe electrodes in neural recordings.