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        Bilateral Cerebral Hemodynamic Response During Unilateral Direct Electrical Stimulation in the Mouse Somatosensory Cortex

        송자경,Minah Suh 한국물리학회 2009 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.54 No.4

        We examined the effects of direct cortical electrical stimulation on the perfusion and the oximetry signals in the whole mouse cortex. An intrinsic optical imaging technique was used to assess the effects of stimulation on cerebral hemodynamics and lateralization. In anesthetized mouse, electrical stimulations with frequencies ranging from 50 to 250 Hz cause bilateral changes in cerebral blood flow and hemoglobin oxygenation signals. In the ipsilateral hemisphere, direct electrical stimulation brings about immediate increases in deoxy hemoglobin concentration and cerebral blood flow. In the contralateral hemisphere, the stimulation also causes immediate weak increases in the deoxy-hemoglobin concentration and immediate intense increases in the blood flow. Overall, the unilateral direct cortical stimulation elicits signicant hemodynamic changes in both the ipsi- and the contralateral sides in the somatosensory cortex of mice and these responses exhibit a frequency dependence. Our data show bilateral hemodynamic changes in the response to electrical stimulation and suggest the likely existence of brain lateralization of neurovascular coupling in the mouse somatosensory cortex. We examined the effects of direct cortical electrical stimulation on the perfusion and the oximetry signals in the whole mouse cortex. An intrinsic optical imaging technique was used to assess the effects of stimulation on cerebral hemodynamics and lateralization. In anesthetized mouse, electrical stimulations with frequencies ranging from 50 to 250 Hz cause bilateral changes in cerebral blood flow and hemoglobin oxygenation signals. In the ipsilateral hemisphere, direct electrical stimulation brings about immediate increases in deoxy hemoglobin concentration and cerebral blood flow. In the contralateral hemisphere, the stimulation also causes immediate weak increases in the deoxy-hemoglobin concentration and immediate intense increases in the blood flow. Overall, the unilateral direct cortical stimulation elicits signicant hemodynamic changes in both the ipsi- and the contralateral sides in the somatosensory cortex of mice and these responses exhibit a frequency dependence. Our data show bilateral hemodynamic changes in the response to electrical stimulation and suggest the likely existence of brain lateralization of neurovascular coupling in the mouse somatosensory cortex.

      • Spatiotemporal dynamics of perfusion and oximetry during ictal discharges in the rat neocortex.

        Zhao, Mingrui,Ma, Hongtao,Suh, Minah,Schwartz, Theodore H The Society 2009 The Journal of neuroscience Vol.29 No.9

        <P>Epileptic events elicit a large focal increase in cerebral blood flow (CBF) to perfuse metabolically active neurons in the focus. Conflicting data exists, however, on whether hemoglobin saturation increases or decreases in the focus and surrounding cortex, and whether CBF increases globally or is decreased in adjacent areas. How these hemodynamic events correlate with actual changes in tissue oxygenation is also not known. Using laser Doppler flowmetry, oxygen microsensors and intrinsic optical imaging spectroscopy, we demonstrate that the dip in hemoglobin in the focus correlates with a profound but temporary decrease in tissue oxygenation despite a large increase in CBF. Furthermore, CBF simultaneously decreases in the cortex immediately adjacent to the focus. These events are then replaced with a longer duration, less focal increase in CBF, cerebral blood volume, and hyperoxygenation, the duration of which correlates with the duration of the seizure. These findings raise the question of whether transient focal hypoxia and vascular steal might contribute to progressive deleterious effects of chronic epilepsy on the adult and developing brain. Possible mechanisms based on recent astrocyte-based models of neurovascular coupling are discussed.</P>

      • Nanoscale live cell optical imaging of the dynamics of intracellular microvesicles in neural cells.

        Lee, Sohee,Heo, Chaejeong,Suh, Minah,Lee, Young Hee American Scientific Publishers 2013 Journal of Nanoscience and Nanotechnology Vol.13 No.11

        <P>Recent advances in biotechnology and imaging technology have provided great opportunities to investigate cellular dynamics. Conventional imaging methods such as transmission electron microscopy, scanning electron microscopy, and atomic force microscopy are powerful techniques for cellular imaging, even at the nanoscale level. However, these techniques have limitations applications in live cell imaging because of the experimental preparation required, namely cell fixation, and the innately small field of view. In this study, we developed a nanoscale optical imaging (NOI) system that combines a conventional optical microscope with a high resolution dark-field condenser (Cytoviva, Inc.) and halogen illuminator. The NOI system's maximum resolution for live cell imaging is around 100 nm. We utilized NOI to investigate the dynamics of intracellular microvesicles of neural cells without immunocytological analysis. In particular, we studied direct, active random, and moderate random dynamic motions of intracellular microvesicles and visualized lysosomal vesicle changes after treatment of cells with a lysosomal inhibitor (NH4Cl). Our results indicate that the NOI system is a feasible, high-resolution optical imaging system for live small organelles that does not require complicated optics or immunocytological staining processes.</P>

      • Hemodynamic surrogates for excitatory membrane potential change during interictal epileptiform events in rat neocortex.

        Ma, Hongtao,Zhao, Mingrui,Suh, Minah,Schwartz, Theodore H American Physiological Society [etc.] 2009 journal of neurophysiology Vol.101 No.5

        <P>Hemodynamic changes in the brain are often used as surrogates for epileptic neuronal activity in both the laboratory and the clinic (e.g., intrinsic signal, functional magnetic resonance imaging and single-photon emission computed tomography) in spite of the fact that perfusion-based signals have been shown to overestimate the population of spiking neurons. In addition, mechanisms of neurovascular coupling that apply during normal cortical processing may not be relevant in pathological circumstances such as epilepsy. For these reasons, we investigated the spatiotemporal dynamics of epileptic neurovascular coupling using voltage-sensitive dyes (VSDs) to generate spatial maps of excitatory membrane activity and intrinsic optical spectroscopy (IOS) to measure deoxy-hemoglobin and total hemoglobin, i.e., cerebral blood volume (CBV), in vivo during interictal spikes in rat neocortex to examine their spatiotemporal correlations. We hypothesized that the IOS signal would correlate spatially with subthreshold excitatory activity, which involves a larger area of cortex than suprathreshold neuronal spiking. However, we found that both perfusion and oximetric signals spatially overshot the extent of the excitatory VSD signal by approximately 2x. Nevertheless, a high correlation could be found at specific time points in the evolution and dissolution of the hemodynamic signals. The increase in deoxy-hemoglobin reached the highest correlation with the excitatory VSD signal earlier than CBV signals although CBV signals correlated equally well at certain time points. The amplitude of the hemodynamic signals had a linear correlation with the amplitude of the VSD signals except for small nonlinearities in the very center of the focus and in the periphery of the surround, indicating a tight spatial coupling. Our data suggest that hemodynamic signals can accurately define the spatial extent of excitatory interictal epileptiform subthreshold membrane activity at specific time points in their evolution.</P>

      • BRAIN RESPONSES TO DIGITAL MUSIC: AN FNIRS STUDY

        Eun-Ju Lee,Kyeong Cheon Cha,Minah Suh 글로벌지식마케팅경영학회 2018 Global Marketing Conference Vol.2018 No.07

        The young generation that was born in the digital age grew up with digital technologies; they listen to music online on web sites like YouTube, which provides access to music by artists from all over the world. We conducted a functional near-infrared spectroscopy (fNIRS) experiment with fifty-six young adults. The human brain generates electrical waves as long as it lives. Since the dynamic nature of brain rhythm is at work in all kinds of human brain function, neuroscientists have used brain rhythm to understand brain function. Since the work of Gerstein and Mandelbrot (1964), many attempts have been made to use random-walk analyses to account for brain responses like the spiking of neurons, cell migration, and motor variability. Like any other biological system, the brain pursues functional efficiency at all levels of operation—in the brain’s case, from the neuronal cell level to the neural network level. Before one can determine the presence of a periodic rhythm versus a random state in brain activation, one must determine whether external stimuli can shape the brain’s modulation pattern. Brain-wave patterns are affected by whether the neural circuit that governs a particular set of brain functions reaches a significant level of activation. The bottom-up processing of external stimuli can be affected by top-down processing; in other words, the execution of higher-order cognitive attention can affect the degree of randomness in the bottom-up processing of external sensory inputs like that of music. Unlike EEG signals, the rhythms of hemodynamic signals are not commonly calculated, possibly because hemodynamic signals are sluggish. The random-walk test on neural time series has been applied only recently to magnetoencephalography (MEG) data (Kipi?ski, K?nig, Sielu?ycki, & Kordecki, 2011), and it has rarely been applied to hemodynamic signals measured with magnetic resonance imaging (MRI) or near-infrared spectroscopy (NIRS). However, since hemodynamic responses are the result of neurovascular coupling—a dynamic event among the brain’s neurons, glias, and vasculatures—it is possible to calculate the degree of randomness of hemodynamic signals as surrogates for neuronal activity. While brain activities are inherently random and noisy in their natural state, when the brain rhythm is modified by music that provides appropriate levels of sensory stimulation, the brain’s signals will begin to reflect the music’s rhythms. This reflection is called “attunement.” The effect of sensori-neural stimulation on hemodynamic responses measured by fNIRS has been reported in neuroscience research that found that auditory stimulation and music elevated the concentrations of oxygenated hemoglobin (HbO2) and total hemoglobin (HbT) in blood flow to certain regions of the brain (Hoshi & Tamura, 1993; Kotilahti et al., 2010; Sakatani, Chen, Lichty, Zuo, & Wang, 1999). However, studies have shown decreases (increases) in children’s (adults’) prefrontal cerebral volume after they play computer games. For example, one study suggested that the level of attention may modulate the directional changes in HbO2 and HbT concentrations (Nagamitsu, Nagano, Yamashita, Takashima, & Matsuishi, 2006). The brains of children who find that a game lacks adequate levels of perceptual stimulation do not require an additional supply of oxygen, but adults who find playing the same game a cognitive challenge require more effort to perform the same task, so they require elevated levels of oxygen in their brains (Ferreri et al., 2014). According to musical theorists, when the brain is entrained, the attention follows the music (London, 2012). When members of the digital generation listen to music, the perceptual stimulation level is likely to related to the degree of randomness in brain responses as well as the quality of the sensory experience. Drawing on the literature review, we predict that TBF is higher for a stimulus that is above OSL than the TBF for a counterpart stimulus that is below OSL. We also predict that the hemodynamic rhythm of related brain regions to music that is above OSL adopts a regular predictable pattern. Hence, we propose the following research hypotheses: H1: Digital music that provides acoustic stimulation near the OSL creates brain responses in the form of higher TBF and lower randomness in HbO2 concentrations than does digital music that provides acoustic stimulation that is below the OSL. Functional Near-infrared Spectroscopy The transparency of biological tissue to light in the near-infrared wavelengths makes NIRS possible. NIRS is non-invasive and portable, and it has a cost advantage. The incident near-infrared light from a transmitting optode (source) is scattered through the tissues, and the reflected light is detected by a receiving optode (detector). The amount of the source light that a tissue absorbs depends on the light’s wave length, and the oxygenation status determines the brain’s absorption of the light. The loss of the intensity that is due to the absorption of the photons can be measured in units of optical density (Zaramella et al., 2001). The changes in [oxy-Hb] and [deoxy-Hb] can be calculated according to the modified Beer-Lambert law (Kocsis, Herman, & Eke, 2006) using two wave lengths of near-infrared light—in our case, 780 and 850nm. We used a 12-channel wireless fNIRS system (Biomedical Optics Lab, Korea University) with sampling rates of 8 ~10 Hz to measure the participants’ hemodynamic response while they watched the videos. The system consists of three light sources and five detectors (a 3×7 grid). The fNIRS probe was attached to each subject’s forehead. The detectors of the lowest line were set along the Fp1 and Fp2 electrode line according to the international 10/20 system. Measurements from channels 1, 2, 11, and 12, which contained noise from movements of the subjects’ heads, hair, and sweat, were excluded from further analysis. Neuroscience research has recorded acoustic stimulation in various regions of the brain, including the temporal brains of newborn babies (Hoshi & Tamura, 1993) and the frontal brains of adults (Sakatani et al., 1999). Since infrared light cannot penetrate hair, brain regions that are not covered by hair, such as the prefrontal cortex, are well-suited to an fNIRS study. When a member of the digital generation listens to music online, the motivation is usually enjoyment, so brain activity changes that are due to popular music should occur in brain areas that are associated with reward-related processing—that is, the medial pre-frontal cortex (mPFC) (Haber & Knutson, 2010). As the mental function of pleasurable experience that is modulated in the medial frontal cortex increases, TBF to this region increases. In particular, the processing of sounds is dominantly modulated by the brain’s right hemisphere (Kaiser, Lutzenberger, Preissl, Ackermann, & Birbaumer, 2000). We analyzed TBF to the right brain area of the mPFC at channel 5 using fNIRS. The research hypothesis predicts that songs that provide strong sensory stimulation above the OSL increase the TBFs of those in the digital generation more than do songs that present a sensory stimulation level that is much under the OSL. TBF can be directly obtained as a product of HbT (Wyatt et al., 1990). After the music began in the experiment, the subjects’ concentrations of HbT increased until HbT reached its peak at around five to eight seconds; then it decreased for the next thirty seconds. There was a divide of hemodynamic responses between the two songs that had more than a million hits per day (A and B) and the remaining three (C, D, and E). We conducted repeated measures of ANOVA on TBF, measured at forty seconds, for the five songs, since TBF at the end of each set of song segments can represent the digital generation’s level of sustained attention. The multivariate test for the model was significant, and the main effect of songs on TBF was significant (Wilk’s Lambda 0.75, F(4,51)=4.249, p=0.005, ???? ). After the forty seconds of each song were over, the TBF levels remained at the highest level for song A, followed in order by Songs B, C, D, and E. Pairwise comparisons after the Bonferroni correction showed that there was a significant divide in the length of time that the TBF levels remained at the highest level between songs A/B and songs C/D/E (p<0.05). Other differences were not significant, possibly because the neural data contained large individual difference variances (between-subject F test: F(1,54) =38.501, .p<0.001,???? ). The results support hypothesis 1. Next, we examined the relationships between TBF and daily hits, and BORP and daily hits. The Pearson correlation coefficient between TBF and daily hits was 0.88 (p<0.05), and the correlation coefficient between BORP and daily hits was -0.96 (p<0.05). Pairwise comparisons after the Bonferroni correction showed that, there was a significant divide in the length of time that the TBF levels remained at the highest level between songs A/B and songs D/E (p<0.05). Other differences were not significant, possibly because neural data contains a large portion of individual variance (between-subject F test: F(1,54) =372.675, p<0.001, ???? ). These results are consistent with our hypothesis 1b that pop music that presents stimulation above OSL can reduce the randomness in hemodynamic signals. The changes in the participants’ hemoglobin concentrations while they listened to popular songs show a mean-reverting tendency with low BORP—a “rhythm” such that a system recovers order and balance in due time. The brain’s response to less popular songs were random-walk processes, which represents a neural drain, a process in which brain fails to recover from oxygen depletion because of boredom. In conclusion, we found that total blood flow to the right medial prefrontal cortex increased less when the young adults were exposed to music that presented acoustic stimulation near the optimal sensory load (OSL) than it did when they were exposed to songs with a level of stimulation much below the OSL. The degrees of hemodynamic randomness decreased significantly while the participants listened to online music that provided near-OSL stimulation. Online popularity, recorded as the number of daily hits, was significantly positively correlated with the total blood flow and negatively correlated with hemodynamic randomness. These findings suggest that a new digital media strategy may be required that provides a sufficient level of sensory stimulation as an essential part of marketing to the digital consumer generation.

      • Measurements of Location-Dependent Nitric Oxide Levels on Skin Surface in relation to Acupuncture Point

        Ha, Yejin,Kim, Misun,Nah, Jiseon,Suh, Minah,Lee, Youngmi Hindawi Publishing Corporation 2012 Evidence-based Complementary and Alternative Medic Vol.2012 No.-

        <P>Location-dependent skin surface's partial nitric oxide pressure (pNO) is studied using highly sensitive amperometric NO microsensor with a small sensing area (diameter = 76 <I><I>μ</I></I>m). The pNO level of LI4 (Hegu) acupuncture point is measured and compared with the pNO level of nonacupuncture point. In addition, the mapping of pNO is carried out over the left wrist skin area one- as well as two-dimensionally. Statistically higher pNO levels near the position of acupuncture points than non-acupuncture points are observed consistently, implying tight relationship between the level of NO release of skin and acupuncture points. The amperometric planar NO microsensor successfully monitors the heterogeneity of skin pNO distribution in high spatial resolution due to its advantageous features such as high sensitivity and small sensing dimension. The current study suggests the direct connection between NO and acupuncture points and possibly provides beneficial information to understand physiological roles and basis of the acupuncture points.</P>

      • GLOBAL POP MUSIC CULTURE IN CYBER SPACE: CAN YOUNG GENERATION’S BRAIN RESPONSES EXPLAIN GLOBAL SUCCESS OF YOUTUBE MUSIC?

        Eun-Ju Lee,Kyoung Cheon Cha,Minah Suh,Hanah Choi 글로벌지식마케팅경영학회 2017 Global Fashion Management Conference Vol.2017 No.07

        Unlike older generation whose consumption of music was bounded by their local culture, today’s young consumers access music beyond cultural boundaries. Many successful pop music in cyber space attracted billions of listeners from all over the world. The young generation born and raised in the digital age, are often thought to have altered sensory-neural characteristics because of their extensive use of electronic device since early childhood. This study investigates a perceptual saturation hypothesis which posits that in order to capture the young generation’s hard-to-get attention, online music must present a high level of energy and rhythm that is near the point of perceptual saturation. We conducted a functional near-infrared spectroscopy (fNIRS) experiment with sixty-four young adults and found that total cerebral blood volume over prefrontal brain area was higher for a song that presents acoustic intensity near the point of perceptual saturation than a counterpart stimulus with lower levels of acoustic intensity. The degrees of prefrontal hemodynamic randomness decreased significantly while the participants listened to YouTube music that provided high levels of acoustic stimulation. Online popularity, recorded as the number of daily hits, was positively correlated with the total cerebral blood volume and negatively correlated with hemodynamic randomness.

      • The Importance of Latency in the Focality of Perfusion and Oxygenation Changes Associated with Triggered after Discharges in Human Cortex

        Ma, Hongtao,Geneslaw, Andrew,Zhao, Mingrui,Suh, Minah,Perry, Challon,Schwartz, Theodore H SAGE Publications 2009 Journal of cerebral blood flow and metabolism Vol.29 No.5

        <P> The spatiotemporal dynamics of neurovascular coupling during epilepsy are not well understood, and there are little data from studies of the human brain. We investigated changes in total hemoglobin (Hbt) and hemoglobin oxygenation in patients undergoing epilepsy surgery with intraoperative intrinsic optical spectroscopy (IOS) during triggered afterdischarges (ADs). We found an early (~0.5 secs) focal dip in hemoglobin oxygenation, arising precisely in the stimulated gyrus that lasted for 11.5 ± 10.0 secs, approximately the length of the AD (10.4 ± 4.4 secs). A later oxygen overshoot and increase in blood volume occurred in the adjacent surrounding gyri. After a significant delay (~20 to 30 secs), the overshoot and blood volume signal became extremely focal to the area of the onset of the AD. A smaller very late undershoot, the last phase of the ‘triphasic’ response, was also identified, although localization was inconsistent. In this study, we show that a ‘late focal overshoot’ and late Hbt signal may be extremely useful, in addition to the early dip, for the localization of seizure onset. It is likely that a separate mechanism underlies the persistent focal increase in cerebral blood volume after a long-duration cortical stimulation, compared with the nonspecific mechanism that causes the initial increase in cerebral blood flow. </P>

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