Changkyun Im

A Flexible Depth Probe Using Liquid Crystal Polymer

We proposed a method of making a flexible depth-type neural probe using liquid crystal polymer. Conventional depth neural probes made of metal or silicon have the limitations of a single recording site per shank or the brittleness of the silicon substrate. To avoid these drawbacks, polymer-based depth neural probes have been developed with biocompatible polymers such as polyimides or parylenes. However, those have suffered from the difficulty of inserting the probes into brain tissues due to their high flexibility, requiring mechanical reinforcements. Herein, we report the first attempt to use a flexible material, liquid crystal polymer (LCP), as a substrate for a depth-type neural probe. The LCP-based probe offers a controllable stiffness vs. flexibility and compatibility with thin-film processes in addition to its inherent characteristics such as high reliability and biocompatibility. In the present study, an LCP neural probe was fabricated to have enough stiffness to penetrate the dura mater of rodent brains without a guide tool or additional reinforcement structures. A simultaneous multichannel neural recording was successfully achieved from the somatosensory motor cortex of the rodents. Immunohistochemistry showed that the electrodes could be inserted into the desired regions in the brain.

Neuronal Responses in the Globus Pallidus during Subthalamic Nucleus Electrical Stimulation in Normal and Parkinson's Disease Model Rats

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been widely used as a treatment for the movement disturbances caused by Parkinsons disease (PD). Despite successful application of DBS, its mechanism of therapeutic effect is not clearly understood. Because PD results from the degeneration of dopamine neurons that affect the basal ganglia (BG) network, investigation of neuronal responses of BG neurons during STN DBS can provide informative insights for the understanding of the mechanism of therapeutic effect. However, it is difficult to observe neuronal activity during DBS because of large stimulation artifacts. Here, we report the observation of neuronal activities of the globus pallidus (GP) in normal and PD model rats during electrical stimulation of the STN. A custom artifact removal technique was devised to enable monitoring of neural activity during stimulation. We investigated how GP neurons responded to STN stimulation at various stimulation frequencies (10, 50, 90 and 130 Hz). It was observed that activities of GP neurons were modulated by stimulation frequency of the STN and significantly inhibited by high frequency stimulation above 50 Hz. These findings suggest that GP neuronal activity is effectively modulated by STN stimulation and strongly dependent on the frequency of stimulation.

Detecting bladder fullness through the ensemble activity patterns of the spinal cord unit population in a somatovisceral convergence environment.

OBJECTIVE Chronic monitoring of the state of the bladder can be used to notify patients with urinary dysfunction when the bladder should be voided. Given that many spinal neurons respond both to somatic and visceral inputs, it is necessary to extract bladder information selectively from the spinal cord. Here, we hypothesize that sensory information with distinct modalities should be represented by the distinct ensemble activity patterns within the neuronal population and, therefore, analyzing the activity patterns of the neuronal population could distinguish bladder fullness from somatic stimuli. APPROACH We simultaneously recorded 26-27 single unit activities in response to bladder distension or tactile stimuli in the dorsal spinal cord of each Sprague-Dawley rat. In order to discriminate between bladder fullness and tactile stimulus inputs, we analyzed the ensemble activity patterns of the entire neuronal population. A support vector machine (SVM) was employed as a classifier, and discrimination performance was measured by k-fold cross-validation tests. MAIN RESULTS Most of the units responding to bladder fullness also responded to the tactile stimuli (88.9-100%). The SVM classifier precisely distinguished the bladder fullness from the somatic input (100%), indicating that the ensemble activity patterns of the unit population in the spinal cord are distinct enough to identify the current input modality. Moreover, our ensemble activity pattern-based classifier showed high robustness against random losses of signals. SIGNIFICANCE This study is the first to demonstrate that the two main issues of electroneurographic monitoring of bladder fullness, low signals and selectiveness, can be solved by an ensemble activity pattern-based approach, improving the feasibility of chronic monitoring of bladder fullness by neural recording.

Hypnotic effect of GABA from rice germ and/or tryptophan in a mouse model of pentothal-induced sleep

Abstractγ-Aminobutyric acid (GABA), a primary inhibitory neurotransmitter, and tryptophan (Trp), a substrate for melatonin, are found in functional foods and exert hypnotic effects. The hypnotic effects of 3 doses of GABA and a combined-preparation of GABA and Trp (GABA+Trp) were investigated in mice. Hypnotic activity was evaluated using pentothal-induced sleep time testing. Treatments included low, middle, and high doses of GABA and GABA+Trp. Low doses of GABA (low-GABA) and low-GABA+Trp reduced sleep latency and significantly (p<0.05) prolonged the sleep time induced by pentothal, compared with controls, although the melatonin concentration in the serum was not affected. On the other hand, the adenosine A1 receptor (AA1R) immunoreactivity in the suprachiasmatic nucleus of the hypothalamus was significantly (p<0.05) increased after administration of low-GABA and/or low-GABA+Trp, compared to controls. Low doses of GABA and/or Trp cause hypnotic effects that may be related to AA1R activation.

Plateau-Shaped Flexible Polymer Microelectrode Array for Neural Recording

Conventional polymer multielectrode arrays (MEAs) have limitations resulting from a high Young’s modulus, including low conformability and gaps between the electrodes and neurons. These gaps are not a problem in soft tissues such as the brain, due to the repopulation phenomenon. However, gaps can result in signal degradation when recording from a fiber bundle, such as the spinal cord. Methods: We propose a method for fabricating flexible polydimethylsiloxane (PDMS)-based MEAs featuring plateau-shaped microelectrodes. The proposed fabrication technique enables the electrodes on the surface of MEAs to make a tight connection to the neurons, because the wire of the MEA is fabricated to be plateau-shaped, as the Young’s modulus of PDMS is similar to soft tissues and PDMS follows the curvature of the neural tissue due to its high conformability compared to the other polymers. Injury caused by the movement of the MEAs can therefore be minimized. Each electrode has a diameter of 130 μm and the 8-channel array has a center-to-center electrode spacing of 300 μm. The signal-to-noise ratio of the plateau-shaped electrodes was larger than that of recessed electrodes because there was no space between the electrode and neural cell. Reliable neural recordings were possible by adjusting the position of the electrode during the experiment without trapping air under the electrodes. Simultaneous multi-channel neural recordings were successfully achieved from the spinal cord of rodents. We describe the fabrication technique, electrode 3D profile, electrode impedance, and MEA performance in in vivo experiments in rodents.

Cross detection for odor of metabolic waste between breast and colorectal cancer using canine olfaction

Although several studies have been performed to detect cancer using canine olfaction, none have investigated whether canine olfaction trained to the specific odor of one cancer is able to detect odor related to other unfamiliar cancers. To resolve this issue, we employed breast and colorectal cancer in vitro, and investigated whether trained dogs to odor related to metabolic waste from breast cancer are able to detect it from colorectal cancer, and vice versa. The culture liquid samples used in the cultivation of cancerous cells (4T1 and CT26) were employed as an experimental group. Two different breeds of dogs were trained for the different cancer odor each other. The dogs were then tested using a double-blind method and cross-test to determine whether they could correctly detect the experimental group, which contains the specific odor for metabolic waste of familiar or unfamiliar cancer. For two cancers, both dogs regardless of whether training or non-training showed that accuracy was over 90%, and sensitivity and specificity were over 0.9, respectively. Through these results, it was verified that the superior olfactory ability of dogs can discriminate odor for metabolic waste of cancer cells from it of benign cells, and that the specific odor for metabolic waste of breast cancer has not significant differences to it of colorectal cancer. That is, it testifies that metabolic waste between breast and colorectal cancer have the common specific odor in vitro. Accordingly, a trained dogs for detecting odor for metabolic waste of breast cancer can perceive it of colorectal cancer, and vice versa. In order to the future work, we will plan in vivo experiment for the two cancers and suggest research as to what kind of cancers have the common specific odor. Furthermore, the relationship between breast and colorectal cancer should be investigated using other research methods.

Performance of odorants inference depending on functional and spatial neuron grouping

This paper presents performance of olfactory neural decoding depending on functional and spatial neural selection. Multi-channel extra-cellular single-unit recording were done by micro-wire electrodes implanted in the mitra/tufted cell layers of the main olfactory bulb (MOB) of anesthetized rates to obtain neural responses to various odors. All neurons are classified according to significant differences response to using t-test (p&#60;0.01). Odor can be robustly inferred by using subpopulations of neurons. The results indicate that the performance of odor inference is highly dependent on the neural selection. Also, we compared different statistical methods correlations of olfactory decoding accuracy. The results show that t-test is better criterion of assessment of neurons capacity than others.

Odor-Dependent Hemodynamic Responses Measured with NIRS in the Main Olfactory Bulb of Anesthetized Rats

In this study, we characterize the hemodynamic changes in the main olfactory bulb of anesthetized Sprague-Dawley (SD) rats with near-infrared spectroscopy (NIRS, ISS Imagent) during presentation of two different odorants. Odorants were presented for 10 seconds with clean air via an automatic odor stimulator. Odorants are: (i) plain air as a reference (Blank), (ii) 2-Heptanone (HEP), (iii) Isopropylbenzene (IB). Our results indicated that a plain air did not cause any change in the concentrations of oxygenated (Δ[HbO2]) and deoxygenated hemoglobin (Δ[Hbr]), but HEP and IB induced strong changes. Furthermore, these odor-specific changes had regional differences within the MOB. Our results suggest that NIRS technology might be a useful tool to identify of various odorants in a non-invasive manner using animals which has a superb olfactory system.