Virtual cooperativity in myoglobin oxygen saturation curve in skeletal muscle in vivo

BACKGROUND: Myoglobin (Mb) is the simplest monomeric hemoprotein and its physicochemical properties including reversible oxygen (O(2))binding in aqueous solution are well known. Unexpectedly, however, its physiological role in intact muscle has not yet been established in spite of the fact that the role of the more complex tetrameric hemoprotein, hemoglobin (Hb), in red cells is well established. Here, I report my new findings on an overlooked property of skeletal Mb. METHODS: I directly observed the oxygenation of Mb in perfused rat skeletal muscle under various states of tissue respiration. A computer-controlled rapid scanning spectrophotometer was used to measure the oxygenation of Mb in the transmission mode. The light beam was focused on the thigh (quadriceps) through a 5-mm-diameter light guide. The transmitted light was conducted to the spectrophotometer through another 5-mm-diameter light guide. Visible difference spectra in the range of 500–650 nm were recorded when O(2 )uptake in the hindlimb muscle reached a constant value after every stepwise change in the O(2 )concentration of the buffer. RESULTS: The O(2 )dissociation curve (ODC) of Mb, when the effluent buffer O(2 )pressure was used as the abscissa, was of a sigmoid shape under normal and increased respiratory conditions whereas it was of rectangular hyperbolic shape under a suppressed respiratory condition. The dissociation curve was shifted toward the right and became more sigmoid with an increase in tissue respiration activity. These observations indicate that an increase in O(2 )demand in tissues makes the O(2 )saturation of Mb more sensitive to O(2 )pressure change in the capillaries and enhances the Mb-mediated O(2 )transfer from Hb to cytochrome oxidase (Cyt. aa(3)), especially under heavy O(2 )demands. CONCLUSION: The virtual cooperativity and O(2 )demand-dependent shifts of the ODC may provide a basis for explaining why Mb has been preserved as monomer during molecular evolution

Paramagnetic artifact and safety criteria for human brain mapping

Biological effects of magnetic field and their safety criteria, especially effects of gradient magnetic field on the cerebral and pulmonary circulation during functional brain mapping are still unclear. Here we estimated that magnetically induced artifacts for the blood oxygenation level- and flow- based functional magnetic resonance imaging are less than 0.1%, and disturbance in the pulmonary circulation is less than 1.3% even if the field strength of magnetic resonance system is risen up to 10 tesla. These paramagnetic effects are considered to be small and harmless during human brain mapping

Regulation of oxygen transport during brain activation: stimulus-induced hemodynamic responses in human and animal cortices

BACKGROUND: The correlation between regional changes in neuronal activity and changes in hemodynamics is a major issue for noninvasive neuroimaging techniques such as functional magnetic resonance imaging (fMRI) and near-infrared optical imaging (NIOI). A tight coupling of these changes has been assumed to elucidate brain function from data obtained with those techniques. In the present study, we investigated the relationship between neuronal activity and hemodynamic responses in the occipital cortex of humans during visual stimulation and in the somatosensory cortex of rats during peripheral nerve stimulation. METHODS: The temporal frequency dependence of macroscopic hemodynamic responses on visual stimuli was investigated in the occipital cortex of humans by simultaneous measurements made using fMRI and NIOI. The stimulus-intensity dependence of both microscopic hemodynamic changes and changes in neuronal activity in response to peripheral nerve stimulation was investigated in animal models by analyzing membrane potential (fluorescence), hemodynamic parameters (visible spectra and laser-Doppler flowmetry), and vessel diameter (image analyzer). RESULTS: Above a certain level of stimulus-intensity, increases in regional cerebral blood flow (rCBF) were accompanied by a decrease in regional cerebral blood volume (rCBV), i.e., dissociation of rCBF and rCBV responses occurred in both the human and animal experiments. Furthermore, the animal experiments revealed that the distribution of increased rCBF and O(2 )spread well beyond the area of neuronal activation, and that the increases showed saturation in the activated area. CONCLUSIONS: These results suggest that above a certain level of neuronal activity, a regulatory mechanism between regional cerebral blood flow (rCBF) and rCBV acts to prevent excess O(2 )inflow into the focally activated area

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)

Dissociation of Stimulus-lnduced Responses in Regional Cerebral Blood Flow and Blood Volume in the Visual Cortex of Humans

To elucidate hemodynamic response in the human visual cortex during visual stimulation, changes in regional cerebral blood flow (rCBF) and cerebral blood volume (rCBV) were investigated using blood oxygenation-level dependent (BOLD) and flow sensitive alternating inversion recovery (FAIR) functional magnetic resonance imaging (BOLD- and FAIR-fMRI) and I6-channel near-infrared optical imaging (NIOI) techniques. A white and black annular checherboard (visual angle: 1.2 to 5.8 degrees) focused on perimacular annulus stimulation of the retina, whose temporal frequencies were 0.5, 1.4, 4.7 and 14 Hz with a central fixation point and gray background, was used as the visual stimulus for perimacular annulus. The stimulus-induced activation area obtained with NIOI corresponded to the one measured with BOLD-fMRI. Nevertheless, a dissociation of stimulus induced responses between the BOLD-fMRI signal and hemoglobin (Hb) parameters obtained with NIOI was found; i.e., changes in BOLD-fMRI signal showed a maximal increase at a temporal frequency of l.4-4.7 Hz, while increases in oxygenated (oxy-Hb) and total hemoglobin (total-Hb) concentrations showed a minimum around the same frequency, and deoxygenated hemoglobin (deoxy-Hb) showed a slight but significant decrease. This dissociation of stimulus-induced responses of the BOLD-fMRI signal and Hb parameters could be simulated as a functions of concentration changes in oxy-Hb, deoxy-Hb, and total-Hb. The temporal frequency dependence of changes in rCBF, estimated from FAIR signal and from the time-course change in total-Hb, was similar to that of the BOLD-fMRI signal change. The present results indicated that stimulus-induced responses of rCBF were dissociated from those of rCBV in the visual cortex of humans during perimacular stimulation at temporal frequency around 1.4-4.7 Hz

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

Correlation analyses between number of letters correctly read and visual function in 27 patients.

The graphs show the relationship between number of letters correctly read vs the I/4 central visual field (A), vs V/4 perifovea (B), vs V/4 periphery (C) and vs acuity (D). (PPTX)</p

Typical examples of analyses of eye movements during reading.

S4 traces for a patient with a visual field of 4° in the right eye (the green line) and 3° in the left eye (the red line). S12 traces for a patient with a visual field of 10° in the right eye (the green line) and 4° in the left eye (the red line). S33 traces for a healthy volunteer with a visual field of 100° in both eyes (right: the green line, left: the red line. Left: Traces of fixation. The size of the circle indicates the length of the residence time at that position. The red lines and circles reflect the movement of the left eye, and the green lines and circles reflect the movement of the right eye. Middle: Angle distribution of the rotation SC direction. The red and green bars denote the left and right eyes, respectively. Right: Traces of eye movements every 0.01 s. The red and green lines denote the traces of the left and right eyes, respectively. Abbreviations: SC, saccade.</p