Makoto Wada

Publications (6)19.94 Total impact

• Article: Neural Correlates of Tactile Temporal-Order Judgment in Humans: an fMRI Study.

  Toshimitsu Takahashi, Kenji Kansaku, Makoto Wada, Satoshi Shibuya, Shigeru Kitazawa
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  ABSTRACT: Little is known about the neuronal mechanisms underlying the temporal ordering of tactile signals. We examined the brain regions involved in judgments of the temporal order of successive taps delivered to both hands. Participants received identical stimuli while engaging in 2 different tasks: Judging the temporal order and judging the numerosity of points of tactile stimulation. Comparisons of the functional magnetic resonance imaging data obtained during the 2 tasks revealed regions that were more strongly activated with the judgments of the temporal order than with the judgments of numerosity under both arms-uncrossed and -crossed conditions: The bilateral premotor cortices, the bilateral middle frontal gyri, the bilateral inferior parietal cortices and supramarginal gyri, and the bilateral posterior part of the superior and middle temporal gyri. Stronger activation was found in some of these areas that implicated for remapping tactile stimuli to spatial coordinates after the participants crossed their arms. The activation in the perisylvian areas overlapped with the human visual-motion-sensitive areas in the posterior part. Based on these results, we propose that the temporal order of tactile signals is determined by combining spatial representations of stimuli in the parietal and prefrontal cortices with representations of "motion" or "changes" in the multisensory perisylvian cortex.
  Cerebral Cortex 07/2012; · 6.54 Impact Factor
• Source

  Available from: PubMed Central

  Article: c-Fos expression during temporal order judgment in mice.

  Makoto Wada, Noriyuki Higo, Shunjiro Moizumi, Shigeru Kitazawa
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  ABSTRACT: The neuronal mechanisms for ordering sensory signals in time still need to be clarified despite a long history of research. To address this issue, we recently developed a behavioral task of temporal order judgment in mice. In the present study, we examined the expression of c-Fos, a marker of neural activation, in mice just after they carried out the temporal order judgment task. The expression of c-Fos was examined in C57BL/6N mice (male, n = 5) that were trained to judge the order of two air-puff stimuli delivered bilaterally to the right and left whiskers with stimulation intervals of 50-750 ms. The mice were rewarded with a food pellet when they responded by orienting their head toward the first stimulus (n = 2) or toward the second stimulus (n = 3) after a visual "go" signal. c-Fos-stained cell densities of these mice (test group) were compared with those of two control groups in coronal brain sections prepared at bregma -2, -1, 0, +1, and +2 mm by applying statistical parametric mapping to the c-Fos immuno-stained sections. The expression of c-Fos was significantly higher in the test group than in the other groups in the bilateral barrel fields of the primary somatosensory cortex, the left secondary somatosensory cortex, the dorsal part of the right secondary auditory cortex. Laminar analyses in the primary somatosensory cortex revealed that c-Fos expression in the test group was most evident in layers II and III, where callosal fibers project. The results suggest that temporal order judgment involves processing bilateral somatosensory signals through the supragranular layers of the primary sensory cortex and in the multimodal sensory areas, including marginal zone between the primary somatosensory cortex and the secondary sensory cortex.
  PLoS ONE 01/2010; 5(5):e10483. · 4.09 Impact Factor
• Article: Statistical parametric mapping of immunopositive cell density.

  Makoto Wada, Kenji Yoshimi, Noriyuki Higo, Yong-Ri Ren, Hideki Mochizuki, Yoshikuni Mizuno, Shigeru Kitazawa
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  ABSTRACT: We developed a new method for comparing immunopositive cell densities across groups of animals and creating statistical parametric maps on standardized sections. As an example, we compared Iba-1 (microglial marker) positive cell densities in rats with (n=6) and without (n=6) unilateral injection of 1-methyl-4-phenylpyridinium salt (MPP+). Immunopositive cells were automatically counted in each animal over a coronal section in the midbrain (bregma -5.9 mm) and a positive cell density map was created for each animal. After the positive cell density map was normalized to a template section from an atlas, positive cell densities of the two groups were compared in each pixel over the section and a statistical parameter (p-value from t-test) was mapped on each pixel. We were able to detect significant increases of microglias in the side of MPP+ injection not only in the substantia nigra pars compacta but also in adjacent white matter. We also applied the same analysis to tyrosine hydroxylase stained sections and detected significant decreases of dopamine neurons in the side of MPP+ injection. The new method was proven to be useful for detecting significant changes of cell densities over the entire area of immunostained sections.
  Neuroscience Research 10/2006; 56(1):96-102. · 2.25 Impact Factor
• Article: Temporal order judgment in mice.

  Makoto Wada, Shunjiro Moizumi, Shigeru Kitazawa
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  ABSTRACT: A temporal order judgment task was developed for mice. After training male mice (C57BL6NCrj, n=15) to poke their noses into a hole, two stimuli (brief puffs of air) were delivered to the whiskers with a fixed interval of 750 ms in one of four orders: right (R)-left (L), L-R, L-L, and R-R. The mice were rewarded when they oriented their heads toward the first (n=5) or second (n=10) stimulus after a visual go signal. The mice were trained for up to 50 days. All mice met the criterion for task achievement (daily correct response rate >70% on 3 consecutive days) in response to unilateral stimuli (L-L and R-R), and 9 of the 15 mice met the criterion for task achievement in response to bilateral stimuli (L-R and R-L). The median periods for task achievement were 15 and 34 days for unilateral and bilateral stimuli, respectively. The correct response rate dropped to approximately the chance level after all whiskers had been removed. The nine successful mice were trained further and tested with smaller interstimulus intervals. The probability of right-first judgment plotted against the stimulation interval was fitted with a sigmoid function (r2=0.92) with asymptotes of 0.29 and 0.73 and a temporal resolution of 160 ms. The sigmoid curve was biased horizontally by 133 ms, reflecting the fact that stimuli delivered simultaneously were judged as left-first rather than right-first. The results show that mice can be trained to judge the temporal order of tactile stimuli delivered to whiskers and that such judgment might be lateralized to the right hemisphere.
  Behavioural Brain Research 02/2005; 157(1):167-75. · 3.42 Impact Factor
• Article: Effects of handedness on tactile temporal order judgment.

  Makoto Wada, Shinya Yamamoto, Shigeru Kitazawa
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  ABSTRACT: We examined effects of handedness on the judgment of temporal order of successive taps delivered to both hands. When the subjects' arms were uncrossed, the temporal resolution (84% correct responses) of right-handed subjects (52 +/- 4 ms, n = 16) was significantly better than that of left-handed subjects (83 +/- 9 ms, n = 16). When their arms were crossed, both groups tended to invert their judgment to a similar extent at intervals as long as 200-300 ms. In the arms crossed condition, right handed subjects inverted their judgment more often in response to left-hand-first stimuli than to right-hand-first stimuli, whereas left-handed subjects did not show the same asymmetry. We infer that hemispheric lateralization, which is generally stronger in right- than in left-handed subjects, contributes to the relatively better temporal resolution of right-handed subjects in the uncrossed condition, as well as to the asymmetric effect of stimulation order in the crossed condition.
  Neuropsychologia 02/2004; 42(14):1887-95. · 3.64 Impact Factor
• Article: Noninvasive bioluminescence imaging of c-fos expression in the mouse barrel cortex

  Makoto Wada, Shigeaki Watanabe, Ung-il Chung, Noriyuki Higo, Tatsuki Taniguchi, Shigeru Kitazawa
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  ABSTRACT: Expression of immediate early genes, such as c-fos, has been extensively used as a marker of neural activity. However, their expression in the brain has so far been examined by using invasive procedures. In this study, we tried to image c-fos expression in the mouse barrel cortex noninvasively by detecting bioluminescence produced by the reporter luciferase. To detect asymmetry in c-fos expression in the bilateral barrel cortices, we used ten Fos-Luc mice and removed long whiskers on one side. After 1 h of exploration in a novel cage, luciferin was intraperitoneally administrated under gas anesthesia and bioluminescence was measured with a cooled CCD camera. We observed moderate but clear emission over the head that was significantly stronger on the side of removal. After regrowth of the whiskers, the same mice had the vibrissae clipped on the other side. Bioluminescence was again dominant on the side of removal. In three of the mice, c-fos expression was examined immunohistochemically. The distribution of bioluminescence generally agreed with that of the c-fos positive cells though the bioluminescence tended to distribute wider, by around 0.5 mm, probably due to scattering of light through the tissues. The results show that expression of c-fos in the mouse barrel cortex can be imaged repeatedly and noninvasively in the living animal.
  Behavioural Brain Research.