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Dae-Shik Kim

Publications and source records attributed to Dae-Shik Kim.

17 recordsLinked to original sources

Total synthesis of the neotropical poison-frog alkaloid (-)-205B.

[reaction: see text]. A stereocontrolled total synthesis of the neotropical poison-frog alkaloid (-)-205B (1) has been achieved, employing a dithiane three-component linchpin coupling, a one-pot sequential construction of the embedded indolizidine ring, and ring-closing metathesis (RCM) to arrive at the novel 8b-azaacenaphthylene ring system comprising the alkaloid. The synthesis proceeded with a longest linear sequence of 19 steps, affording (-)-1 in 5.6% overall yield.

Alkaloids↗

Motor control in basal ganglia circuits using fMRI and brain atlas approaches.

In this study, we examined how the motor, premotor and associative basal ganglia territories process movement parameters such as the complexity and the frequency of movement. Twelve right-handed volunteers were studied using EPI BOLD contrast (3 T) while performing audio-paced finger tapping tasks designed to differentiate basal ganglia territories. Tasks varied movement complexity (repetitive index tapping, simple sequence of finger movements and complex sequence of 10 moves) and frequency (from 0.5 to 3 Hz). Activation maps were coregistered onto a 3-D brain atlas derived from post-mortem brains. Three main patterns of activation were observed. In the posterior putamen and the sensorimotor cortex, signal increased with movement frequency but not with movement complexity. In premotor areas, the anterior putamen and the ventral posterolateral thalamus, signal increased regularly with increasing movement frequency and complexity. In rostral frontal areas, the caudate nucleus, the subthalamic nucleus and the ventral anterior/ventrolateral thalamus, signal increased mainly during the complex task and the high frequency task (3 Hz). These data show the different roles of motor, premotor and associative basal ganglia circuits in the processing of motor-related operations and suggest that activation can be precisely located within the entire circuitry of the basal ganglia.

Adolescent↗

How does DWI correlate with white matter structures?

Diffusion-weighted MRI (DWI) is widely used to characterize brain white matter (WM), particularly through the use of diffusion tensor imaging (DTI). In this study the spatial characteristics of DWI in WM of cat visual cortex were investigated at 9.4T at very high resolution. It is shown that the spatial extent of the WM tract as measured from the DWI images depends highly on the b-value. In particular, when the diffusion gradient is applied perpendicular to the main direction of the fiber tract, the estimated thickness of the tract at the commonly used b-value of 1000 s/mm2 exceeds by 50% the thickness as it appears on a T2-weighted image. Only at b-values greater than 6000 s/mm2 does the thickness of the tract approach the thickness characterized by the T2-weighted image and that observed on histological slices of the same area. Further analysis of these results indicates that the choice of b-value of 1000 s/mm2 may not be optimal for the demarcation of anisotropic WM structures. DWI at high b-value may contain spatial information that is more specific to WM tracts.

Animals↗

3-D diffusion tensor axonal tracking shows distinct SMA and pre-SMA projections to the human striatum.

Studies in non-human primates have shown that medial premotor projections to the striatum are characterized as a set of distinct circuits conveying different type of information. This study assesses the anatomical projections from the supplementary motor area (SMA), pre-SMA and motor cortex (MC) to the human striatum using diffusion tensor imaging (DTI) axonal tracking. Eight right-handed volunteers were studied at 1.5 T using DTI axonal tracking. A connectivity matrix was computed, which tested for connections between cortical areas (MC, SMA and pre-SMA) and subcortical areas (posterior, middle and anterior putamen and the head of the caudate nucleus) in each hemisphere. Pre-SMA projections to the striatum were located rostral to SMA projections to the striatum. The SMA and the MC were similarly connected to the posterior and middle putamen and not to the anterior striatum. These data show that the MC and SMA have connections with similar parts of the sensorimotor compartment of the human striatum, whereas the pre-SMA sends connections to more rostral parts of the striatum, including the associative compartment.

Adult↗

Multicomponent linchpin coupling of silyl dithianes employing an N-Ts aziridine as the second electrophile: synthesis of (-)-indolizidine 223AB.

[reaction: see text] An efficient, stereocontrolled assembly of the indolizidine alkaloid, (-)-indolizidine 223AB, exploiting a three-component linchpin coupling employing an N-Ts aziridine as the second electrophile, followed by a one-pot sequential construction of the indolizidine ring system, has been achieved. The longest linear sequence was 10 steps, proceeding in 10% overall yield.

Aziridines↗

A comparison of hemodynamic and neural responses in cat visual cortex using complex stimuli.

We compare fMRI-BOLD responses in anesthetized cats with local field potentials (LFPs), aggregate high-frequency responses (analog-Mua) and spiking activity recorded in primary and higher visual cortex of alert animals. The similarity of the activations in these electrophysiological signals to those in the BOLD is quantified by counting recording sites where different stimuli elicit the same relative activation as in the imaging experiments. Using artificial stimuli, a comparison of BOLD and LFP strongly depends on the frequency range used. Stimulating with complex or natural stimuli reduces this frequency dependence and yields a good match of LFP and BOLD. In general, this match is best between 20 and 50 Hz. The measures of high-frequency activity behave qualitatively different: the responses of the analog-Mua match those of the LFP; the spiking activity shows a low concordance with the BOLD signal. This dissociation of BOLD and spiking activity is most prominent upon stimulation with natural stimuli.

Animals↗

Diffusion tensor fiber tracking shows distinct corticostriatal circuits in humans.

A landmark of corticostriatal connectivity in nonhuman primates is that cortical connections are organized into a set of discrete circuits. Each circuit is assumed to perform distinct behavioral functions. In animals, most connectivity studies are performed using invasive tracing methods, which are nonapplicable in humans. To test the proposal that corticostriatal connections are organized as multiple circuits in humans, we used diffusion tensor imaging axonal tracking, a new magnetic resonance technique that allows demonstration of fiber tracts in a noninvasive manner. Diffusion tensor imaging-based fiber tracking showed that the posterior (sensorimotor), anterior (associative), and ventral (limbic) compartments of the human striatum have specific connections with the cortex, and particularly the frontal lobes. These results provide the first direct demonstration of distinct corticostriatal connections in humans.

Adult↗

Spatial relationship between neuronal activity and BOLD functional MRI.

Despite the ubiquitous use of functional magnetic resonance imaging (fMRI), the extent to which the magnitude and spatial scale of the fMRI signal correlates with neuronal activity is poorly understood. In this study, we directly compared single and multiunit neuronal activity with blood oxygenation level-dependent (BOLD) fMRI responses across a large area of the cat area 18. Our data suggest that at the scale of several millimeters, the BOLD contrast correlates linearly with the underlying neuronal activity. At the level of individual electrode recording sites, however, the correlation between the two signals varied substantially. We conclude from our study that T(2)*-based positive BOLD signals are a robust predictor for neuronal activity only at supra-millimeter spatial scales.

Animals↗

Retinotopic mapping in cat visual cortex using high-field functional magnetic resonance imaging.

In the field of neuroscience, there has always been a need for imaging techniques that provide high-resolution, large field-of-view measurements of neural activity. Functional MRI has this capability, but the link between the blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal and neural activity is indirect. High magnetic field strengths (>3 T) improve the strength and specificity of the BOLD signal, but there are additional concerns about imaging artifacts at high field. We have tested the capabilities of ultra high field fMRI in the anesthetized juvenile cat, demonstrating rapid, non-invasive retinotopic mapping of early visual areas. Maps of topographic organization and measured cortical magnification factors are in good agreement with electrophysiological studies. Measurement precision was estimated at 1 mm. This mapping, performed with an MRI scanner at ultra high field (9.4 T), demonstrates the capabilities of high-resolution functional mapping of the visual system at ultra high field.

Animals↗

Lasonolide A: structural revision and total synthesis.

The proposed structure of lasonolide A was synthesized employing radical cyclization reactions of beta-alkoxyacrylates for preparation of the tetrahydropyranyl units A and B, but the spectroscopic data did not match those of the natural product. Both enantiomers of a revised structure featuring 17E,25Z double bonds were synthesized, and the (-)-isomer was found to be the biologically active enantiomer.

Antineoplastic Agents↗

Conventional DTI vs. slow and fast diffusion tensors in cat visual cortex.

Diffusion tensor imaging (DTI) uses water diffusion anisotropy in axonal fibers to provide a tool for analyzing and tracking those fibers in brain white matter. In the present work, multidirectional diffusion MRI data were collected from a cat brain and decomposed into slow and fast diffusion tensors and directly compared with conventional DTI data from the same imaging slice. The fractional anisotropy of the slow diffusing component (D(slow)) was significantly higher than the anisotropy measured by conventional DTI while reflecting a similar directionality and appeared to account for most of the anisotropy observed in gray matter, where the fiber density is notoriously low. Preliminary results of fiber tracking based on the slow diffusion component are shown. Fibers generated based on the slow diffusion component appear to follow the vertical fibers in gray matter. D(slow)TI may provide a way for increasing the sensitivity to anisotropic structures in cortical gray matter.

Animals↗

High-field magnetic resonance techniques for brain research.

High-field magnetic resonance imaging scanners with a static magnetic field of 3 Tesla or higher are becoming ubiquitous in clinical and basic neurosciences. Given the high cost and complexity of operation, it is important to ask whether or not and how the use of high-field magnets can be beneficial for the neurosciences. What new questions can be addressed? Which new insights can we expect from these new tools? In addition, what are the limitations of these new techniques? This review discusses the three most important applications of the high-field magnetic resonance techniques for the neuroscience community: first, functional magnetic resonance imaging, second, in vivo spectroscopy, and third, in vivo fiber tracking on the basis of diffusion tensor imaging.

Animals↗

In vivo mapping of functional domains and axonal connectivity in cat visual cortex using magnetic resonance imaging.

Noninvasive cognitive neuroimaging studies based on functional magnetic resonance imaging (fMRI) are of ever-increasing importance for basic and clinical neurosciences. The explanatory power of fMRI could be greatly expanded, however, if the pattern of the neuronal circuitry underlying functional activation could be made visible in an equally noninvasive manner. In this study, blood oxygenation level-dependent (BOLD)-based fMRI and diffusion tensor imaging (DTI) were performed in the same cat visual cortex, and the foci of fMRI activation utilized as seeding points for 3D DTI fiber reconstruction algorithms, thus providing the map of the axonal circuitry underlying visual information processing. The methods developed in this study will lay the foundation for in vivo neuroanatomy and the ability for noninvasive longitudinal studies of brain development.

Algorithms↗

Investigating directed cortical interactions in time-resolved fMRI data using vector autoregressive modeling and Granger causality mapping.

We present a framework aimed to reveal directed interactions of activated brain areas using time-resolved fMRI and vector autoregressive (VAR) modeling in the context of Granger causality. After describing the underlying mathematical concepts, we present simulations helping to characterize the conditions under which VAR modeling and Granger causality can reveal directed interactions from fluctuations in BOLD-like signal time courses. We apply the proposed approach to a dynamic sensorimotor mapping paradigm. In an event-related fMRI experiment, subjects performed a visuomotor mapping task for which the mapping of two stimuli ("faces" vs "houses") to two responses ("left" or "right") alternated periodically between the two possible mappings. Besides expected activity in sensory and motor areas, a fronto-parietal network was found to be active during presentation of a cue indicating a change in the stimulus-response (S-R) mapping. The observed network includes the superior parietal lobule and premotor areas. These areas might be involved in setting up and maintaining stimulus-response associations. The Granger causality analysis revealed a directed influence exerted by the left lateral prefrontal cortex and premotor areas on the left posterior parietal cortex.

Brain Mapping↗

Functional activation using apparent diffusion coefficient-dependent contrast allows better spatial localization to the neuronal activity: evidence using diffusion tensor imaging and fiber tracking.

Recent studies suggested that functional activation using apparent diffusion coefficient (ADC) contrast can be used to detect synchronized functional MRI (fMRI) signal changes during brain activation. Such changes may reflect better spatial localization to the smaller vessels, which are closely coupled to the true neuronal activation. Since it is generally believed that there are neural pathways among neuronally relevant areas, methods that would allow clear delineation of such pathways could help validate the neuronal relevance of the activated functional areas. The development of diffusion tensor imaging (DTI) has shown promise in detailed nerve fiber tracking. In this report, DTI was adopted to track the fiber connections among the discrete areas determined using the ADC contrast, in an effort to confirm the neuronal origin of these activated areas. As a comparison, activated areas using blood oxygenation level-dependent (BOLD) contrast were also obtained. Our results showed that the areas determined by the ADC contrast consistently allowed better fiber tracking within, while the BOLD-activated areas were more spatially diffused due to the smearing effect of brain vasculature, rendering the task of fiber tracking more difficult. This observation provides converging evidence that the activated areas using ADC contrast are more closely coupled to the neuronal activity than those using BOLD contrast.

Brain↗

Origin of negative blood oxygenation level-dependent fMRI signals.

Functional magnetic resonance imaging (fMRI) techniques are based on the assumption that changes in spike activity are accompanied by modulation in the blood oxygenation level-dependent (BOLD) signal. In addition to conventional increases in BOLD signals, sustained negative BOLD signal changes are occasionally observed and are thought to reflect a decrease in neural activity. In this study, the source of the negative BOLD signal was investigated using T2*-weighted BOLD and cerebral blood volume (CBV) techniques in isoflurane-anesthetized cats. A positive BOLD signal change was observed in the primary visual cortex (area 18) during visual stimulation, while a prolonged negative BOLD change was detected in the adjacent suprasylvian gyrus containing higher-order visual areas. However, in both regions neurons are known to increase spike activity during visual stimulation. The positive and negative BOLD amplitudes obtained at six spatial-frequency stimuli were highly correlated, and negative BOLD percent changes were approximately one third of the positive changes. Area 18 with positive BOLD signals experienced an increase in CBV, while regions exhibiting the prolonged negative BOLD signal underwent a decrease in CBV. The CBV changes in area 18 were faster than the BOLD signals from the same corresponding region and the CBV changes in the suprasylvian gyrus. The results support the notion that reallocation of cortical blood resources could overcome a local demand for increased cerebral blood flow induced by increased neural activity. The findings of this study imply that caution should be taken when interpreting the negative BOLD signals as a decrease in neuronal activity.

Animals↗