Encephalitis of unknown etiology with anti-GluR epsilon2 autoantibody, showing divergent neuroradiologic and clinical findings.
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Biomedical subjects
Publications and source records attributed to Soichiro Nomura.
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Although cognitive efforts were reported to elicit global autonomic arousal, which cognitive processes associate with autonomic arousal has not been clear. We investigated autonomic arousal using event-related skin conductance responses (SCRs) during the Stroop color-word task. After baseline SCR deflections were determined in each trial block, SCRs were compared between cognitive conflict conditions (incongruent vs. congruent stimuli), between tasks assigned (word reading vs. color naming), and between erroneous and correct responses. Baseline SCRs were significantly greater at the beginning of each trial block. SCRs were significantly greater with incongruent than congruent stimuli while SCRs differed little between word reading and color naming. SCRs were greater when responses were incorrect. The results suggested that autonomic arousal occurs during cognitive conflict resolution in addition to mental set adoption for a task and in error awareness.
The splicing of 26 nucleotides in the coding region of the X-box binding protein-1 (XBP-1) transcript to generate a mature active transcription factor is a part of the unfolded protein response to intracellular endoplasmic reticulum stress. In this study, we demonstrated that XBP-1 splicing is promptly induced in the rat brain including the hippocampus by both inescapable electric foot shock (IS) and pharmacologically manipulated activation of 5-hydroxytryptamine release in a dose-dependent manner. By administering ketanserin, a 5-hydroxytryptamine 2A antagonist, however, we could only partially block the increased splicing by IS and observed that the splicing was not influenced by lithium carbonate pretreatment. Although it is still unclear whether the enhanced unfolded protein response functions neuroprotectively by modulating the rate of general translation and increasing chaperone proteins or whether it eventually induces cellular damage by triggering apoptosis, the present results indicate the possible existence of a new adaptive intracellular signaling pathway in the brain that responds to environmentally challenged behavioral stress loading.
Until recently, early visual areas (V1/V2) were believed to respond mainly to illusory contours (ICs). At present, however, functional neuroimaging suggests that the human lateral occipital complex (LOC), a higher tier than V2, responds strongly to ICs and that IC-related activation in V1/V2 in fact might be driven by feedback input from the LOC. When Kanizsa-type ICs are modified by rounding the corners of the inducers and misaligning them slightly, the impression of an enclosed salient region (SR) remains, although ICs no longer are perceived. Stanley and Rubin (Stanley, D.A., Rubin, N., 2003. fMRI activation in response to illusory contours and salient regions in the human lateral occipital complex. Neuron, 37, 323-331) found that the LOC responded to SR, suggesting that the LOC subserves a rapid but crude region-based segmentation process preceding boundary completion in V1/V2. The present study compared the time course of cortical responses to ICs with those to SR using high-density (74-channel) event-related potentials (ERPs). Scalp mapping and statistical analysis indicated that shared negative modulation for ICs and SR was distributed bilaterally over the lateral occipital scalp at a latency of 70 to 180 ms. Slightly later, a weak negative modulation occurred with ICs but not SR at the occipital pole scalp from 170 to 180 ms. Dipoles for early and late modulations were fitted optimally in the LOC and occipital pole, respectively. The present results suggested that IC-related cortical activation could be separated into region-based segmentation and subsequent boundary completion.
Wistar rats exposed to inescapable foot shocks (IS) for 2 wk exhibited PTSD-like bi-directional changes similar to avoidance/numbing and hyperarousal symptoms when placed in a shuttle box. Paroxetine administration after IS reduced the hyperarousal-like behavior, and its therapeutic effect on avoidance/numbing-like behavior was also significant. Further, F344 rats, which were more vulnerable to various kinds of stressors, showed more significant 'bi-directional changes' than Wistar rats. Thus, the paradigm we have developed could serve as a useful PTSD model because of its face, predictive, and construct validity. Moreover, the intensity of IS dose-dependently induced PTSD-like behaviors and hypo-activity in a shuttle box, similar to the 'avoidance/numbing' that reappeared in a square open field. These findings further support the construct validity of this paradigm. Both electro-convulsive shock treatment before and after IS ameliorated the PTSD-like behaviors in this model, so electro-convulsive therapy may be an effective method for prevention and medical treatment of PTSD in the future. On the other hand, pretreatment with fluvoxamine before IS did not have a significant effect, and its improving effect after IS was only observed for 'hyperarousal' behavior. Lastly, we recently developed a useful criterion, which is represented as a 'bi-directional index', for separating real PTSD rats from those exposed to IS.
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BACKGROUND: In addition to character dimensions, personality includes temperament dimensions, defined as individual differences in implicit associative learning responses to environmental stimuli processed by unconscious memories. We examined whether temperament dimensions were associated with patterns of unconscious emotional responses of an autonomic nature. METHODS: From 70 healthy men, high and low novelty-seeking (NS) groups and high and low harm-avoidance (HA) groups were selected using scores on the Tridimensional Personality Questionnaire measuring temperament dimensions. Emotionally negative, neutral, and positive visual stimuli were presented subliminally using backward masking, and skin conductance responses (SCRs) were measured as an autonomic index of emotional responses. Skin conductance responses to the three emotional stimulus conditions were compared between groups. RESULTS: Skin conductance responses in the high NS group were significantly greater than in the low NS group when positive or negative emotional stimuli were presented but not neutral stimuli. Skin conductance responses in the high HA group were significantly greater than in the low HA group for stimuli of all three valences. CONCLUSIONS: Autonomic response patterns to unconscious emotional perception differed between NS and HA, suggesting that different dimensions of temperament may be associated with different patterns of unconscious emotional responses. Novelty seeking and HA may be associated with specificity and susceptibility of preattentive emotional perception, respectively.
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To investigate interhemispheric differences concerning unconscious human emotional responses processed, we measured human skin conductance responses (SCRs) to masked (unseen) emotional stimuli presented to left or right visual fields. Backward masking was used to preclude conscious processing of emotional stimuli. Masked negative or neutral emotional pictures from the International Affective Picture System (IAPS) were presented to 11 right-handed male volunteers. Mean SCR for negative emotional stimuli presented to the left visual field was significantly greater than mean SCRs for negative emotional stimuli to the right visual field and for neutral stimuli to the left or right visual fields. Thus, the right rather than the left hemisphere appears to respond to preattentive negative emotional stimuli.
To better understand neurochemical and psychopharmacological aspects of post-traumatic stress disorder (PTSD), it is necessary to establish an animal model of PTSD in which behavioral changes persist after the initial traumatization. We administered inescapable electric foot-shock (IS) to male Wistar rats in a shuttle-box with the gate closed. With or without paroxetine (PRX; belonging to selective serotonin reuptake inhibitors) treatment for 2 weeks after IS, we performed an avoidance/escape task session in the shuttle-box using signal lights as non-specific anxiogenic stimulants. Locomotor activity decreased before the task session and avoidance behavior increased during the session. Two weeks of PRX administration reduced hypervigilant behavior during the task session. We considered these behavioral changes as representative of numbing/avoidance and hypervigilance, referred to as bi-directional changes in PTSD.
We evaluated brain activity using 64-channel visual evoked potentials (VEPs) while subjects perceived apparent motion in depth. Checkerboard patterns (CBPs) within small and large circles were presented in turn as experimental conditions. Motion in depth was perceived when the CBP in the large circle was coarser than in the small circle; when coarseness did not change, no motion in depth was perceived. As control conditions only fine or coarse CBPs were presented. We used ANOVA to compare VEPs associated with experimental vs. control conditions and with coarse vs. fine CBPs. Negative potentials at a latency near 190 ms showed statistically significant interactions between these comparisons in the right lateral occipital and posterior parietal areas when apparent motion in depth was perceived. This suggests that higher tiers of the dorsal stream mediate this motion perception.
Differences in cognitive processing between spatially possible and impossible figures were investigated using event-related potentials (ERPs). Two types of figures with identical luminance and equivalent spatial frequency were used as visual stimuli: possible three-dimensional figures (drawn with perspective and existing in the three-dimensional world) and impossible figures (drawn with perspective but not existing in the three-dimensional world). High-density electroencephalographic recording (72 channels) was performed for analysis of ERPs accompanying perception of each figure type; amplitude differences between the conditions were considered neurophysiologic correlates to perceptual differences between possible and impossible objects. Low-resolution brain electromagnetic tomography (LORETA) was used to identify the current source related to the differences. Compared with impossible three-dimensional figures, perception of possible figures showed a significant negative potential increase in the right inferior occipitotemporal region between 350 and 389 ms of latency. The current source was localized to the right fusiform gyrus. The results suggest that right fusiform gyrus is involved in discrimination between spatially possible and impossible objects.
Although still controversial, iron deficiency has been indicated as one of the risk factors for developing neuroleptic-induced extrapyramidal symptoms (EPSs), including akathisia, dystonia, and neuroleptic malignant syndrome. Here we report our experience of iron supplementation and alternating neuroleptics for treating Parkinsonism in a schizophrenic female patient having severe iron deficient anemia.
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Medication algorithms based on the best evidence available together with expert consensus are considered to promote logical consistent clinical decision making in the choice of antidepressant drugs. We report our preliminary results using the modified algorithm established by the Japanese Psychopharmacology Algorithm Project (JPAP). Subjects were 24 patients with major depressive disorders who presented to the outpatient clinic of the Department of Psychiatry at the National Defense Medical College prior to any treatment for the current episode. Ultimately, 15 patients recovered with treatment according to our protocol, including 7 who recovered upon treatment with first-line drugs; the most effective of these was paroxetine, followed by fluvoxamine and then milnacipran. Six patients recovered with second-line treatments. Among these, a combination of milnacipran and lithium was most effective, with recovery of 4 of 4 patients. We have formed a strong impression that augmentation therapy, especially with milnacipran plus lithium, is likely to be effective if the first-line antidepressant is ineffective. Investigation of more cases will be needed to confirm or refine details of the algorithm and, more generally, to determine the best approach to antidepressant medication.
To better understand neuroscientific aspects of posttraumatic stress disorder (PTSD), it is necessary to establish an animal model of PTSD in which behavioral changes persist after initial traumatization. We administered inescapable footshock (IS) to male Wistar rats in a shuttle-box (inescapable stress session), and after 2 weeks we performed an avoidance/escape task session in the shuttle-box using signal lights as anxiogenic external stimuli. Rats exposed to IS beforehand exhibited PTSD-like bi-directional behavioral changes, that is, "avoidance/numbing" (e.g. decreased activity, reactivity, and interest in surroundings) and "hyperarousal" (e.g. irritability and exaggerated responsiveness to external stimuli). Concretely speaking, in a relatively calm situation, spontaneous locomotion decreased during a 5-min adaptation period just before the avoidance/escape task session. On the other hand, in a stressful situation after starting the task session, not only avoidance responses to external stimuli (signal lights) but also gate-crossings during inter-trial interval increased. Accordingly, the paradigm used here could serve as a useful model of PTSD. We administered paroxetine (PRX) to rats just after IS for 2 weeks to examine its chronic effect on our animal model. Two weeks of PRX treatment significantly reduced hyperarousal-like behaviors, but no effect on avoidance/numbing-like ones was manifested.
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