Biomedical subjects

Keisuke Toyama

Publications and source records attributed to Keisuke Toyama.

8 recordsLinked to original sources

PubMed2004

A neural correlate of reward-based behavioral learning in caudate nucleus: a functional magnetic resonance imaging study of a stochastic decision task.

Humans can acquire appropriate behaviors that maximize rewards on a trial-and-error basis. Recent electrophysiological and imaging studies have demonstrated that neural activity in the midbrain and ventral striatum encodes the error of reward prediction. However, it is yet to be examined whether the striatum is the main locus of reward-based behavioral learning. To address this, we conducted functional magnetic resonance imaging (fMRI) of a stochastic decision task involving monetary rewards, in which subjects had to learn behaviors involving different task difficulties that were controlled by probability. We performed a correlation analysis of fMRI data by using the explanatory variables derived from subject behaviors. We found that activity in the caudate nucleus was correlated with short-term reward and, furthermore, paralleled the magnitude of a subject's behavioral change during learning. In addition, we confirmed that this parallelism between learning and activity in the caudate nucleus is robustly maintained even when we vary task difficulty by controlling the probability. These findings suggest that the caudate nucleus is one of the main loci for reward-based behavioral learning.

Adult↗

PubMed2004

Hierarchical Bayesian estimation for MEG inverse problem.

Source current estimation from MEG measurement is an ill-posed problem that requires prior assumptions about brain activity and an efficient estimation algorithm. In this article, we propose a new hierarchical Bayesian method introducing a hierarchical prior that can effectively incorporate both structural and functional MRI data. In our method, the variance of the source current at each source location is considered an unknown parameter and estimated from the observed MEG data and prior information by using the Variational Bayesian method. The fMRI information can be imposed as prior information on the variance distribution rather than the variance itself so that it gives a soft constraint on the variance. A spatial smoothness constraint, that the neural activity within a few millimeter radius tends to be similar due to the neural connections, can also be implemented as a hierarchical prior. The proposed method provides a unified theory to deal with the following three situations: (1) MEG with no other data, (2) MEG with structural MRI data on cortical surfaces, and (3) MEG with both structural MRI and fMRI data. We investigated the performance of our method and conventional linear inverse methods under these three conditions. Simulation results indicate that our method has better accuracy and spatial resolution than the conventional linear inverse methods under all three conditions. It is also shown that accuracy of our method improves as MRI and fMRI information becomes available. Simulation results demonstrate that our method appropriately resolves the inverse problem even if fMRI data convey inaccurate information, while the Wiener filter method is seriously deteriorated by inaccurate fMRI information.

Algorithms↗

PubMed2003

Development of functional thalamocortical synapses studied with current source-density analysis in whole forebrain slices in the rat.

We analysed the laminar distribution of transmembrane currents from embryonic (E) day 17 until adulthood after selective thalamic stimulation in slices of rat forebrain to study the development of functional thalamocortical and cortico-cortical connections. At E18 to birth a short-latency current sink was observed in the subplate and layer 6, which was decreased, but not fully abolished in a cobalt containing solution or after the application of glutamate receptor blockers (APV and DNQX). This indicated that embryonic thalamic axons were capable of conducting action potentials to the cortex and some of them had already formed functional synapses there. Between birth and P3, when thalamic axons were completing their upward growth, a sink gradually appeared more superficially in the dense cortical plate and synchronously, a current source aroused in layer 5. Both sinks and sources completely disappeared after blocking synaptic transmission. The adult-like distribution of CSDs became apparent after P7. The component in layer 6 cannot be blocked completely after this age suggesting antidromic activation. This study demonstrated that cells of the lowest layers of the cortex received functional thalamic input before birth and that thalamocortical axons formed synapses with more superficial cells as they grew into the cortical plate.

Animals↗

PubMed2003

Effects of TNFalpha on the growth and sensitivity to cytosine arabinoside of blast progenitors in acute myelogenous leukemia with special reference to the role of NF-kappaB.

Leukemic blasts in acute myelogenous leukemia (AML) are derived from a minor population of cells called blast progenitors. Hematopoietic growth factors (HGFs) stimulate their growth and simultaneously sensitize them to cytosine arabinoside (Ara-C), a cell-cycle-specific cytotoxic drug. Since tumor necrosis factor alpha (TNFalpha) modifies HGF activities, we examined the effects of TNFalpha in combination with HGFs on in vitro growth and Ara-C sensitivity of AML blast progenitors in patient samples. TNFalpha variably affected HGF-supported colony formation and the self-renewal of blast progenitors. However, the combination of TNFalpha with IL-3 uniformly rendered blast progenitors more resistant to Ara-C irrespective of whether TNFalpha suppressed or augmented IL-3-supported growth, indicating that TNFalpha regulates the Ara-C sensitivity of leukemic progenitors independently of their cell cycle status. Since nuclear factor-kappaB (NF-kappaB) is activated by TNFalpha and induces expression of prosurvival genes, effects of the antisense oligodeoxynucleotides to NF-kappaB subunits, p65 and p50, were examined. Antisense oligodeoxynucleotides sensitized HL60 cells to Ara-C but rendered leukemic progenitors in patient samples even more resistant to Ara-C in the presence of TNFalpha and IL-3 in combination, indicating that NF-kappaB is involved in the Ara-C sensitivity of leukemic blast progenitors but may exert opposite dual functions, namely protection from and induction of apoptosis, under different conditions.

Adult↗

PubMed2002

Magnetic responses of human visual cortex to illusory contours.

To examine the neural mechanism underlying illusory-contour perception, we measured the magnetic responses of the human visual cortex to an abutting-line grating inducing illusory contours (test stimulus) and a non-abutting-line grating (control stimulus) using the technique of magnetoencephalography (MEG). In the initial latency period of 60-80 ms, the MEG response to the test stimulus was nearly identical with that to the control stimulus, but in the subsequent period of 80-150 ms, the former was larger than the latter. The origin of the peak MEG response to the test stimulus was estimated to be in the vicinity of striate cortex/extrastriate visual cortex for two of the four subjects. These results suggest that, in accord with those of the previous electrophysiological and functional magnetic resonance imaging studies, illusory-contour signals are generated in the very early stage(s) of processing in the primate visual cortex.

Adult↗

PubMed2002

Surround suppression in the human visual cortex: an analysis using magnetoencephalography.

The responses of neurons in the primate and cat primary visual cortices (V1s) to the stimuli within their classical receptive fields (CRFs) are markedly suppressed by the surrounding stimuli outside CRFs. In the present study, we show that a similar suppressive effect occurs for visually evoked magnetic responses in the human visual cortex. The initial peak amplitude of the magnetic response (at a latency of around 90 ms) to a test grating accompanied by high-contrast surround gratings was smaller than that for the test without the surround. Current source localization with a single dipole model indicated that the initial response originated from cortical activity near the occipital pole in the contralateral hemisphere to the visual stimulation. The peak amplitude for the test decreased with increasing surround contrast, and increased with increasing test contrast. The contrast dependence and the early development of the surround suppression were in agreement with the results of the V1 single-cell studies of monkeys and cats. We suggest that the surround suppression of the initial peak amplitude of the magnetic response may be ascribed to the inhibition of the neural activity at the early processing stage(s), presumably at V1, in the human visual cortex.

Adult↗

PubMed1996

Imaging a Computational Process in the Visual Cortex.

Visual perception is a computational process reconstructing the 3D visual world based on the 2D images viewed by the two eyes, which inherently contains ill-posed problems due to information deficiency. A typical example is the correspondence problem in finding partner points between the two retinal images. A neural network model for solution of the correspondence problem was proposed by Marr (1982, Vision. San Francisco: Freeman and Co.), constructed of groups of neurons selectively responsive to different disparities of visual stimuli shown to the two eyes. This model solves the correspondence problem as a relaxation process of excitation working between the neuronal groups responding to the same disparity antagonized by inhibition working between those responding to different disparity. Optical recording of responses evoked in the rat visual cortical slice by electrical stimulation of the white matter demonstrated the relaxation process of excitation antagonized by inhibition. Copyright 1996 Elsevier Science Ltd.

Journal Article↗

PubMedDate not supplied

Regulation of drug transporters by the farnesoid X receptor in mice.

The farnesoid X receptor (FXR, NR1H4) regulates bile acid and lipid homeostasis by acting as an intracellular bile acid-sensing transcription factor, resulting in altered expression of enzymes and transporters involved in bile acid synthesis and transport. Here, we quantitatively analyzed the alterations in expression levels of drug transporters, mainly organic anion-transporting polypeptides (oatp), in wild-type and FXR-null mice to evaluate the role of FXR in their expression and regulation by cholic acid. Changes in the mRNA amounts in liver, kidney, small intestine, and testis in FXR-null mice fed with or without a supplement of 0.5% cholic acid in the diet were analyzed by semiquantitative RT-PCR. In FXR-null mice, the mRNA levels of oatp1, oatp2, oatp3, and octn1 were lower than those of wild-type mice in kidney and testis, while there was no difference in liver or small intestine. Cholic acid feeding led to significantly decreased levels of expression of oatp1 and oct1 and an increased level of expression of oatp2 in wild-type mouse liver. In FXR-null mice, oatp1 and other transporters were downregulated in liver, kidney, and testis, whereas small intestine ASBT, octn2, and pept1 were upregulated. Our results suggested that FXR is involved in the transcriptional regulation of oatp and other transporters in a tissue-specific manner. Furthermore, the effect of cholic acid treatment indicates the involvement of regulatory mechanism(s) other than FXR.

Animals↗