Role of the left posterior middle temporal gyrus in shape recognition and its reconstruction during drawing: A study combining transcranial magnetic stimulation and functional near infrared spectroscopy.

There are numerous reports of enhanced or emerged visual arts abilities in patients with semantic impairment. These reports led to the theory that a loss of function on the language side of the brain can result in changes of ability to draw and/or to paint. Further, the left posterior middle temporal gyrus (l-pMTG) has been revealed to contribute to the higher control semantic mechanisms with objects recognition and integration of visual information, within a widely distributed network of the left hemisphere. Nevertheless, the theory has not been fully studied in neural bases. The aim of this study is to examine role of the l-pMTG on shape recognition and its reconstruction within drawing behavior, by using a combining method of the repetitive transcranial magnetic stimulation (rTMS) and functional near-infrared spectroscopy (fNIRS). Eighteen healthy participants received a low frequency inhibitory rTMS to their l-pMTG during the drawing task of the Benton Visual Retention Test (BVRT). There was a significant decrease of the mean accuracy of reproductions in the Complex designs of the BVRT, compared to the Simple and Medium designs. The fNIRS data showed strong negative correlations with the results of the BVRT. Though our hypothesis had a contradiction that rTMS would have inhibited the brain activity in the stimulated site, the results suggest that shape recognition and its reconstruction such as the BVRT require neural activations of the l-TL as well as that of the l-pMTG.

Depression is associated with discoordination between heart rate variability and physical acceleration in older women.

Background and Aims: It is well known that depression is closely associated with the autonomic nervous system and physical acceleration (PA), which may cause functional time-deviance between these two parameters. Exploring this relationship is important in sustaining the mental and physical health of older adults in daily life. However, few studies have assessed the relationship between depression and the coordination of parasympathetic nervous activity (PSNA) and PA. The present study was designed to investigate whether the coordination between PSNA and PA is associated with the mental state of healthy volunteers in normal daily lives and the underlying mechanism. Methods: In total, 95 adult women were divided into non-older and older groups comprising 50 (aged 20-59 years) and 45 (aged 60-85 years) women, respectively. PSNA and PA data were simultaneously obtained every minute for 24 h during the free-moving day using the ActiveTracer accelerometer. Lag time was determined as the time difference between PSNA and PA, and it was introduced as a parameter of %lag0, which is the percent ratio of the lag = 0 min between PSNA and PA in 1 h. The General Health Questionnaire 28 (GHQ28) was used to evaluate the effects of psychological distress, including depression. Results: In the hour before sleep, %lag0 was significantly lower in older women (38.7 ± 6.4) who had higher GHQ28 values (subscale D = 0, n = 12) compared with that in older women (19.4 ± 10.5) with lower values (subscale D ≧ 1, n = 33) (p < 0.05). Conclusion: Impairments in coordination between PSNA and PA are significantly associated with depression in older women, particularly in the hour before sleep on free-moving days.

Characterization of forehead blood flow bias on NIRS signals during neural activation with a verbal fluency task.

The major problem of near-infrared spectroscopy (NIRS) for brain activity measurement during verbal fluency task is the overlapping forehead scalp blood flow (FBF) on the target cerebral blood flow (CBF). There could be among-individual differences in the influence of FBF on CBF. We investigated effects of FBF on CBF by comparing signals obtained through a laser Doppler flowmeter (LDF) and NIRS using the modified Beer-Lambert Law (MBLL). Among 25 healthy individuals, 7 participants showed a strong correlation between LDF and NIRS signals (rs >0.500). There were no significant differences according to age or sex. Subsequently, we applied the hemodynamic separation method to the values calculated using the MBLL (Δ[oxy-Hb]M): to separate the concentration of oxygenated hemoglobin in the forehead (Δ[oxy-Hb]F) and cerebral cortex (Δ[oxy-Hb]C). First, we found that the influence of Δ[oxy-Hb]F on Δ[oxy-Hb]C in the high rs group was almost twice as large as that in the low rs group. Second, presence of sex and age differences in the influence of Δ[oxy-Hb]F on Δ[oxy-Hb]C were suggested. Based on the results, we discuss the factors affecting FBF and the resulting variations in NIRS signals.

Importance of two-dimensional gaze analyses in the assessment of reading performance in patients with retinitis pigmentosa.

The causes of reading difficulties in people with peripheral visual field loss are not fully understood. We conducted a two-dimensional gaze analysis on eye movements during reading in patients with retinitis pigmentosa to investigate the causes of reading difficulties in relation to the central visual field using a binocular eye mark recorder (EMR-9). Twenty-seven patients with retinitis pigmentosa whose central visual field narrowed to ≤ 20° using Goldmann kinetic perimetry (I/4 target) and this present study included eight healthy participants. The participants' visual acuities were corrected to better than +0.4 logMAR. Correlations and multivariate regression analyses were investigated between the number of letters read correctly, the I/4 central visual field, V/4 perifoveal and peripheral visual field, and visual acuity. Multivariate regression analysis revealed that all these parameters played almost equal roles in the number of letters read correctly. In the two-dimensional gaze analysis, the task performance time of patients during reading increased as the I/4 central visual field narrowed. The task performance time was more clearly correlated with the rotation saccade (r = 0.428, p <0.05) and the distance of the vertical direction (ΣY) of eye movements (r = 0.624, p < 0.01), but not with regressive saccade and the distance of the horizontal direction (ΣX). Visual acuity was correlated with the task performance time (-0.436, <0.05) but not with eye movement directionality. Reading difficulties in patients with retinitis pigmentosa result from impaired eye movement directionality. Understanding eye measurements for people with tunnel vision required a two-dimensional gaze analysis. The two-dimensional gaze analysis also showed that the involvement of the perifoveal and peripheral visual fields, visual acuity, and I/4 central visual field was important for reading in people with tunnel vision.

Inter-Brain Synchronization During Sandplay Therapy: Individual Analyses.

Interactions between the client (Cl) and therapist (Th) evolve therapeutic relationships in psychotherapy. An interpersonal link or therapeutic space is implicitly developed, wherein certain important elements are expressed and shared. However, neural basis of psychotherapy, especially of non-verbal modalities, have scarcely been explored. Therefore, we examined the neural backgrounds of such therapeutic alliances during sandplay, a powerful art/play therapy technique. Real-time and simultaneous measurement of hemodynamics was conducted in the prefrontal cortex (PFC) of Cl-Th pairs participating in sandplay and subsequent interview sessions through multichannel near-infrared spectroscopy. As sandplay is highly individualized, and no two sessions and products (sandtrays) are the same, we expected variation in interactive patterns in the Cl-Th pairs. Nevertheless, we observed a statistically significant correlation between the spatio-temporal patterns in signals produced by the homologous regions of the brains. During the sandplay condition, significant correlations were obtained in the lateral PFC and frontopolar (FP) regions in the real Cl-Th pairs. Furthermore, a significant correlation was observed in the FP region for the interview condition. The correlations found in our study were explained as a "remote" synchronization (i.e., unconnected peripheral oscillators synchronizing through a hub maintaining free desynchronized dynamics) between two subjects in a pair, possibly representing the neural foundation of empathy, which arises commonly in sandplay therapy (ST).

Coordination between heart rate variability and physical activity may be diminished by fatigability in non-older women in the hour before sleep.

Fatigability is related to several diseases as well as the autonomic nervous system. We investigated whether fatigability is associated with coordination between physical acceleration (PA) and parasympathetic nervous activity (PSNA) in women. Overall, 95 women were divided into non-old (n = 50; age: 22-59 years) and old (n = 45; age: ≥60 years) groups. PSNA and PA data were simultaneously obtained every minute for 24 h. We defined %lag0 as the percent ratio of lag = 0 min between PSNA and PA in 1 h. Cornell Medical Index was used to determine the degrees of physical and psychological symptoms. In the non-older group in the hour before sleep, the participants with high fatigability scores had significantly lower %lag0 than those with low fatigability (p < 0.05). Additionally, those with higher fatigability combined with exhaustion in the morning had significantly lower %lag0 than those without exhaustion in the hour before sleep (p < 0.05) but not in the hour after waking up. These results suggest that fatigability in non-older women was associated with loss of coordination between PSNA and PA in the hour before sleep. Additionally, exhaustion in the morning may be related to loss coordination of PSNA and PA during the previous night.

Parasympathetic Nervous Activity Associated with Discoordination Between Physical Acceleration and Heart Rate Variability in Patients with Sleep Apnea.

Sleep apnea syndrome (SAS) often accompanies alterations in heart rate variability (HRV). The severity of SAS is sometimes evaluated using the oxygen desaturation index (ODI). We hypothesized that effects of the autonomic nervous system could be involved in the coordination between HRV and physical acceleration during free movement in patients with SAS. Among 33 women aged 60 years or older, 19 had a high ODI (>5). Their HRV and physical acceleration were simultaneously obtained every minute for 24 hours. The low frequency/high frequency (LF/HF) ratio and the high frequency in normalized units (HFnu) were used as HRV indices. Low levels of %Lag0, defined as the percentage of the lag = 0 min in 1 h, indicated coordination between physical acceleration and HRV. Nineteen participants were divided into group A (high %Lag0 before sleep [n = 9]) or group B (low %Lag0 [n = 10]). In group B participants with a high ODI and low %Lag0 in the hour after waking, HFnu was significantly increased compared to that in group A participants with high ODI and high %Lag0 in the hour after waking (p < 0.05). These results suggest that close associations between high ODI and discoordination between HRV and physical acceleration may be due to higher parasympathetic nervous system activity after waking.

Monte Carlo Modeling of Shortwave-Infrared Fluorescence Photon Migration in Voxelized Media for the Detection of Breast Cancer.

Recent progress regarding shortwave-infrared (SWIR) molecular imaging technology has inspired another modality of noninvasive diagnosis for early breast cancer detection in which previous mammography or sonography would be compensated. Although a SWIR fluorescence image of a small breast cancer of several millimeters was obtained from experiments with small animals, detailed numerical analyses before clinical application were required, since various parameters such as size as well as body hair differed between humans and small experimental animals. In this study, the feasibility of SWIR was compared against visible (VIS) and near-infrared (NIR) region, using the Monte Carlo simulation in voxelized media. In this model, due to the implementation of the excitation gradient, fluorescence is based on rational mechanisms, whereas fluorescence within breast cancer is spatially proportional to excitation intensity. The fluence map of SWIR simulation with excitation gradient indicated signals near the upper surface of the cancer, and stronger than those of the NIR. Furthermore, there was a dependency on the fluence signal distribution on the contour of the breast tissue, as well as the internal structure, due to the implementation of digital anatomical data for the Visible Human Project. The fluorescence signal was observed to become weaker in all regions including the VIS, the NIR, and the SWIR region, when fluorescence-labeled cancer either became smaller or was embedded in a deeper area. However, fluorescence in SWIR alone from a cancer of 4 mm diameter was judged to be detectable at a depth of 1.4 cm.

Effects of Light and Sound on the Prefrontal Cortex Activation and Emotional Function: A Functional Near-Infrared Spectroscopy Study.

We constructed a near infrared spectroscopy-based real-time feedback system to estimate the subjects' emotional states using the changes in oxygenated hemoglobin concentration [Δ(oxy-Hb)] in the prefrontal cortex (PFC). Using this system, we investigated the influences of continual mild and equivocal stimuli consisting of lights and a reconstructed waterfall sound on Δ[oxy-Hb] in the PFC. The visual (light) and auditory (sound) stimuli changed randomly and independently, depending on the emotional states of the individual subjects. The emotional states induced by the stimuli were examined via a questionnaire rated on an 11-point scale, from +5 (pleasant) to -5 (unpleasant), through 0 (neutral), after the 5-min experiments. Results from 757 subjects revealed that Δ[oxy-Hb] in the PFC exhibited a weak, but significant, correlation with emotional change, with the given continual and mild stimuli similar to that experienced in response to the intense pleasant/unpleasant stimuli. Based on the results we discuss the generation of pleasant/unpleasant weak emotional change induced by mild and weak stimuli such as light and sound.

11.7 T MR Imaging Revealed Dilatation of Virchow-Robin Spaces within Hippocampus in Maternally Lipopolysaccharide-exposed Rats.

PURPOSE: 11.7 Tesla MRI was examined to detect Virchow-Robin spaces (VRSs) smaller than 100 µm in the rat brain. The effects of maternal exposure to lipopolysaccharide (LPS) were evaluated on basis of the number of dilated VRSs in the offspring rat brain. METHODS: T2-weighted MRI with an in-plane resolution up to 78 µm (repetition time = 5000 ms, echo time = 35 ms, slice thickness = 250 µm, imaging plane, coronal) was applied to identify VRSs. The dilated VRSs were counted in the rat brain at 5 and 10 weeks of age. The dams of half the number in each group were treated with LPS during pregnancy, and the remaining half was employed as control. LPS injection in gestation period was used to simulate maternal infections, the method of which was widely accepted as a rat model inducing neuropsychiatric disorders in the offspring. Effects of LPS exposure on the offspring rat brain were statistically investigated. RESULTS: VRSs as small as 78 µm were successfully detected by the ultra high-field MRI. All dilated VRSs were observed within lacunosum molecular layer of hippocampus, and molecular and granular layers of dentate gyrus around hippocampal fissure. In juvenile rats (5 weeks of age), the number of dilated VRSs was significantly increased in the prenatal LPS exposed rat brain (12.9 ± 2.4, n = 7) than in the control (5.3 ± 1.5, n = 7, P < 0.05), while in young adult rats (10 weeks of age), there was no significant difference in the number between the prenatal LPS exposed rat brain (3.6 ± 0.9, n = 5) and the control (2.6 ± 0.4, n = 5). CONCLUSION: The results of the present study suggested that maternal infection might cause dilatation of VRSs through neural damages especially in the dentate gyrus of the offspring rats. Thus, ultra high-field MRI can offer a promising diagnostic tool capable of determining the location of neonatal brain damage caused by maternal infections.

An Analysis of the Factor Model on the Workload of Nursing Staff Using a Hospital Management Tool.

We developed a tool that allows a medical facility to offer efficient nursing care with limited human resources by optimizing the distribution of hospital ward nursing tasks. The use of information and communications technology to visualize daily workloads and make use of quantified workload data is important for identifying management elements that allow the efficient allocation of personnel and tasks. The goal of this study was to utilize data from the ward management tool that we developed to consider workflow processes for nursing staff and the relationships between the nursing competence of the nursing staff and the patients' conditions and how these impact on workloads. We found a correlation between workload and staff competence. With respect to the teamwork index and patient condition, structural equation modeling analysis using the intensity of nursing care needs and degree of independent daily living showed that patient condition had a meaningful effect on workload.

Estimation of Skin Blood Flow Artefacts in NIRS Signals During a Verbal Fluency Task.

The aim of this study was to clarify effects of skin (scalp) blood flow on functional near infrared spectroscopy (fNIRS) during a verbal fluency task. In the present study, to estimate the influence of skin blood flow on fNIRS signals, we conducted examinations on 19 healthy volunteers (39.9±13.1 years, 11 male and 8 female subjects). We simultaneously measured the fNIRS signals, skin blood flow (i.e., flow, velocity, and number of red blood cells [RBC]), and pulse wave rates using a multimodal fNIRS system. We found that the effects of skin blood flow, measured by the degree of interference of the flow, velocity, and number of RBCs, and pulse wave rates, on NIRS signals varied considerably across subjects. Further, by using the above physiological parameters, we evaluated application of the independent component analysis algorithm proposed by Molgedey and Schuster (MS-ICA) to remove skin blood flow artefacts from fNIRS signals.

NKp46 regulates the production of serine proteases and IL-22 in human mast cells in urticaria pigmentosa.

NKp46 (natural cytotoxic receptor 1/CD335) is expressed on natural killer cells and Th2-type innate lymphocytes. However, NKp46 expression in human mast cells has not yet been reported. Here, we explored the expression of, and possible role played by, NKp46 in such cells. NKp46 protein was expressed in human mast cells in urticaria pigmentosa principally of the tryptase-positive/chymase-negative type (MCT), but not in human non-neoplastic skin mast cells of the tryptase-positive/chymase-positive (MCTC) type. NKp46 expression was also evident in the human neoplastic mast cell line HMC1.2. NKp46 knockdown changed the phenotype of this cell line from MCT to MCTC and downregulated GrB production, but did not influence IL-22 production. An agonistic anti-NKp46 antibody upregulated production of GrB and IL-22, but did not change the MCT-like phenotype of HMC1.2 cells. NKp46 was thus involved in the production of serine proteases and IL-22 in human mast cells.

In vivo magnetic resonance imaging at 11.7 Tesla visualized the effects of neonatal transection of infraorbital nerve upon primary and secondary trigeminal pathways in rats.

Using 11.7T ultra high-field T2-weighted MRI, the present study aimed to investigate pathological changes of primary and secondary trigeminal pathways following neonatal transection of infraorbital nerve in rats. The trigeminal pathways consist of spinal trigeminal tract, trigeminal sensory nuclear complex, medial lemniscus, ventromedial portion of external medullary lamina and ventral posterior nucleus of thalamus. By selecting optimum parameters of MRI such as repetition time, echo time, and slice orientation, this study visualized the trigeminal pathways in rats without any contrast agents. Pathological changes due to the nerve transection were found at 8 weeks of age as a marked reduction of the areas of the trigeminal pathways connecting from the injured nerve. In addition, T2-weighted MR images of the trigeminal nerve trunk and the spinal trigeminal tract suggest a communication of CSF through the trigeminal nerve between the inside and outside of the brain stem. These results support the utility of ultra high-field MRI system for noninvasive assessment of effects of trigeminal nerve injury upon the trigeminal pathways.

fMRI evidence of improved visual function in patients with progressive retinitis pigmentosa by eye-movement training.

To evaluate changes in the visual processing of patients with progressive retinitis pigmentosa (RP) who acquired improved reading capability by eye-movement training (EMT), we performed functional magnetic resonance imaging (fMRI) before and after EMT. Six patients with bilateral concentric contraction caused by pigmentary degeneration of the retina and 6 normal volunteers were recruited. Patients were given EMT for 5 min every day for 8-10 months. fMRI data were acquired on a 3.0-Tesla scanner while subjects were performing reading tasks. In separate experiments (before fMRI scanning), visual performances for readings were measured by the number of letters read correctly in 5 min. Before EMT, activation areas of the primary visual cortex of patients were 48.8% of those of the controls. The number of letters read correctly in 5 min was 36.6% of those by the normal volunteers. After EMT, the activation areas of patients were not changed or slightly decreased; however, reading performance increased in 5 of 6 patients, which was 46.6% of that of the normal volunteers (p< 0.05). After EMT, increased activity was observed in the frontal eye fields (FEFs) of all patients; however, increases in the activity of the parietal eye fields (PEFs) were observed only in patients who showed greater improvement in reading capability. The improvement in reading ability of the patients after EMT is regarded as an effect of the increased activity of FEF and PEF, which play important roles in attention and working memory as well as the regulation of eye movements.

Ischemic pretreatment delays ischemic brain vasospasm injury in gerbils.

Three experiments were conducted for the present study. First, to elucidate the mechanism and functional significance underlying ischemic vasoconstriction, we investigated the relationship between arteriolar constriction and tissue energy metabolism during bilateral common carotid artery occlusion in gerbils. Second, to identify differences in the postischemic recovery of physiologic parameters between short and prolonged brain ischemia, we measured changes in regional cerebral blood flow, microvessel diameter, brain temperature, and electrophysiologic response. Third, to explore the physiological mechanism of ischemic tolerance, we studied vascular response and intracerebral oxygenation states after acute global ischemia with and without pretreatment by mild ischemic stress. Here, we identify one of the physiologic mechanisms of the ischemic tolerance caused by brief ischemic pretreatment.

Influence of subjective happiness on the prefrontal brain activity: an fNIRS study.

Focusing on the relationship between subjective happiness (SH) and emotional changes, we examined influences of SH on emotion-related prefrontal activity using multichannel NIRS. The International Affective Picture System (IAPS) was used to evoke emotional changes. Subjects were a total of 18 right-handed healthy students. Frequency of picture-induced increases in oxygenated haemoglobin (oxy-Hb) was evaluated. Subjects with a high SH score had a higher frequency of increased oxy-Hb in the left prefrontal cortex (PFC) while viewing pleasant pictures, whereas they showed a lower frequency in the right PFC while viewing unpleasant pictures. It is well known that the left PFC and right PFC are engaged in different ways in the emotional processes. Although further investigations are required, the present results indicate that the SH level influences the right-left differences in emotion-related prefrontal activity.

Novel sonomicrometry of ex vivo diaphragm after phrenic nerve injury: Role of matrix metalloproteinases.

Extracellular matrix (ECM) proteins and their proteolytic enzymes, matrix metalloproteinases (MMPs), implicate in neuromuscular junctions (NMJs) function during development. However, their pathophysiological mechanisms in the diaphragm remain obscure, because a well-characterized ex vivo experimental system has still been lacking. In the study, we aim to develop a novel ex vivo method of sonomicrometry and evaluate validity of the method with a mouse diaphragm twitch after phrenic nerve injury. In an ex vivo experiment using phrenic nerve-injured mice, diaphragm twitch during electrical pulse stimulation of phrenic nerve was transiently suppressed on day 1. Recombinant MMPs administered in recording solution exerted dose-responsive suppression on the diaphragm twitch in normal mice tissue. Furthermore, gelatinolytic and immunoblot experiments were performed to evaluate MMPs' involvement and NMJs' insults. After nerve injury, (1) in vivo levels of MMPs were transiently upregulated at day 1 and (2) expressions of ECM proteins, agrin (nicotinic acetylcholine receptor stabilizer) and laminin, were transiently reduced at day 1 in the diaphragm. These alterations were cancelled by preinjection of the MMP inhibitor. In conclusion, MMPs hamper NMJ synaptic function in association with the impairment of ECM milieu. Our novel experimental method using ex vivo sonomicrometry is necessary for examining the molecular pathophysiolgy for the dysfunction of NMJs in the diaphragm.

Effects of timing and duration of hypothermia on survival in an experimental gerbil model of global ischaemia.

PURPOSE: Despite the use of animal models to study post-cardiac-arrest resuscitation, the effects of hypothermia on physiological circulatory parameters are still not fully understood. In this study, using a gerbil model of global ischaemia/reperfusion, we aimed to assess the effects of hypothermia on physiological parameters and evaluated the optimal timing for the induction of hypothermia to achieve a better survival rate. METHODS: Survival rates at 72 h after reperfusion were evaluated by varying the degree of hypothermia and/or duration of ischaemia, and then examined by varying induction timing and/or extending the duration of ischaemia. Physiological parameters were measured using an intravital microscopy system. RESULTS: Under normothermic cerebral ischaemia, the survival rate was dramatically decreased by the induction of 15-20 min of ischaemia. Induction of hypothermia significantly improved the survival rate only when it occurred less than 10 min after ischaemic onset. In the hypothermia-treated groups, post-ischaemic hyperperfusion was significantly suppressed, and post-ischaemic vasoconstriction of the pial arteriole was prevented. CONCLUSIONS: Hypothermia-induced suppression of post-ischaemic hyperperfusion and the prevention of vasoconstriction of the pial arteriole play an important role in improving the survival rate after global ischaemia/reperfusion, but the time window for induction of hypothermia remains relatively narrow.

Water-diffusion slowdown in the human visual cortex on visual stimulation precedes vascular responses.

We used magnetic resonance imaging (MRI) to investigate the temporal dynamics of changes in water diffusion and blood oxygenation level-dependent (BOLD) responses in the brain cortex of eight subjects undergoing visual stimulation, and compared them with changes of the vascular hemoglobin content (oxygenated, deoxygenated, and total hemoglobin) acquired simultaneously from intrinsic optical recordings (near infrared spectroscopy). The group average rise time for the diffusion MRI signal was statistically significantly shorter than those of the BOLD signal and total hemoglobin content optical signal, which is assumed to be the fastest observable vascular signal. In addition, the group average decay time for the diffusion MRI also was shortest. The overall time courses of the BOLD and optical signals were strongly correlated, but the covariance was weaker with the diffusion MRI response. These results suggest that the observed decrease in water diffusion reflects early events that precede the vascular responses, which could originate from changes in the extravascular tissue.