Abnormal pontine activation in pathological laughing as shown by functional magnetic resonance imaging.

To explore the aetiology of pathological laughing, a 65-year-old woman with pathological laughing was examined by 3-T functional magnetic resonance imaging (fMRI) before and after treatment with drugs. Here, we report that the patient consistently showed exaggerated pontine activation during the performance of three tasks before treatment, whereas abnormal pontine activation was no longer found after successful treatment with the selective serotonin reuptake inhibitor, paroxetine. Our findings in this first fMRI study of pathological laughing suggest that serotonergic replacement decreases the aberrant activity in a circuit that involves the pons.

Functional magnetic resonance imaging evidence for a representation of the ear in human primary somatosensory cortex: comparison with magnetoencephalography study.

Our previous study (T. Nihashi et al., 2001, Neuro- Image 13: 295-304), using magnetoencephalography (MEG), revealed somatotopy of the ear in the human primary somatosensory cortex (SI); that is, the signals following stimulation of the ear reach both the neck and face areas of the SI. However, since this was the first report on somatotopy of the ear in humans, we performed an fMRI activation study to confirm the somatotopic representation, and compared the electrical activity by MEG and the cerebral blood flow change by fMRI. We studied eight healthy subjects using 3-T MRI. We stimulated three parts of the left ear: the helix, the lobulus, and the tragus. First, we identified the location of the ear area in the SI based on our previous MEG study, in which equivalent current dipoles (ECDs) were located in the neck and/or face areas of the SI. Then, we determined the search volume as a sphere with a 15-mm radius, which was placed in the neck and/or face area. We analyzed whether or not fMRI activation occurred inside such spheres. Stimulation of the helix activated the neck area of the SI in four of eight subjects, and both the neck and face areas in two. No activation was observed in two subjects. Stimulation of the lobulus activated the neck area in one subject, the face area in two, both in four, and neither in one. Stimulation of the tragus activated the face in four, both in three, and neither in one. These fMRI findings confirm the result of MEG that the representation of the ear in the SI is separated into neck and face areas.

Hemodynamics of local cerebral blood flow induced by somatosensory stimulation under normoxia and hyperoxia in rats.

We observed changes in the local cerebral blood flow (LCBF), red blood cell (RBC) concentration and RBC velocity in alpha-chloralose anesthetized rats using laser-Doppler flowmetry during activation of the somatosensory cortex following electrical stimulation of the hind paw under hyperoxia (PaO(2)=513.5+/-48.4 mmHg; mean+/-S.D.) and normoxia (PaO(2)=106.4+/-8.4 mmHg). Electrical stimuli of 5 and 10 Hz (pulse width 0.1 ms) with an intensity of 1.5 mA were applied for 5 s (n=13 at 5 Hz, n=9 at 10 Hz). Baseline levels of LCBF and RBC concentration under hyperoxia were, respectively, 5.6+/-3.3 and 8.8+/-3.0% lower than those under normoxia (P<0.05), and that of RBC velocity under hyperoxia was slightly higher than that under normoxia (NS), suggesting mild vasoconstriction at rest under hyperoxia. At 5 Hz stimulation, after normalization to each baseline level, normalized response magnitudes of LCBF, RBC concentration and RBC velocity under hyperoxia were, respectively, 68.2+/-48.0, 71.1+/-65.5 and 66.0+/-56.3% greater than those under normoxia (P<0.05). At 10-Hz stimulation, normalized response magnitudes of LCBF and RBC concentration under hyperoxia were, respectively, 44.6+/-32.0 and 55.9+/-43.5% greater than those under normoxia (P<0.05), although a significant difference in the normalized response magnitude of RBC velocity was not detected between both conditions. The evoked LCBF under hyperoxia increased earlier, by approximately 0.15 s, than that under normoxia regardless of the stimulus frequency (P<0.05). These results suggest the involvement of oxygen interaction on the regulation of LCBF during neuronal activation.

Bayesian technique for investigating linearity in event-related BOLD fMRI.

Event-related BOLD fMRI data is modeled as a linear time-invariant system. Together with Bayesian inference techniques, a statistical test is developed for rigorously detecting linearity/nonlinearity in the BOLD response system. The test is applied to data collected from eight subjects using an event-related paradigm with a switching checkerboard as the visual stimulus. Analyzed as a group, the results clearly find the response to be nonlinear. When each subject is analyzed individually, however, the results are predominantly nonlinear, but there is some evidence to suggest that there may be a crossover from a linear to a nonlinear regime and vice versa. This could be important when estimating physiological parameters for individuals. Additionally, estimates of the hemodynamic response function and corresponding response were obtained, but there was no consistent appearance of a poststimulus undershoot in the event-related BOLD response.

Hyperoxia modified activation-induced blood oxygenation level-dependent response of human visual cortex (V1): an event-related functional magnetic resonance imaging study.

To investigate the effect that hyperoxia has on the blood oxygenation level-dependent (BOLD) response to visual stimulation of human V1, an event-related functional magnetic resonance imaging technique was applied. The event-related paradigm consisted of 2 s of stimulation by a checkerboard reversing at a frequency of 8 Hz, followed by 18 s of control scans. The peak height and peak time of the BOLD response curves were compared under normoxic and hyperoxic conditions. It was found that the peak height was larger and the peak time shorter for hyperoxia than for normoxia. These results suggest that hyperoxia modified the activation-induced hemodynamic response of human V1.

Temporal characteristics of event-related BOLD response and visual-evoked potentials from checkerboard stimulation of human V1: a comparison between different control features.

This work is concerned with the temporal characteristics of event-related blood oxygenation level-dependent (ER-BOLD) and visual-evoked potential (VEP) signals produced by checkerboard stimulation of human V1. The study investigated whether different control features produce different amplitude VEPs, and if so, whether this corresponds to different ER-BOLD responses. The results showed that there was a difference in the amplitude of the P1-N1 components of the VEPs, and also in the magnitude and extent of the ER-BOLD responses. These results suggest the possibility that the P1-N1 components may be related to the difference in the magnitude and extent of the ER-BOLD response. Magn Reson Med 45:212-216, 2001.

Modulation of evoked cerebral blood flow under excessive blood supply and hyperoxic conditions.

We measured the field potential and local cerebral blood flow (LCBF) using laser-Doppler flowmetry in alpha-chloralose anesthetized rats during activation of the somatosensory cortex by electrical stimulation of the hind paw under independent administration of additional carbon dioxide and oxygen. The aim of this study was to test the hypothesis that the increase in LCBF during activation of the cortex (evoked LCBF) is not directed toward supplying oxygen for oxidative metabolism. Under the hypercapnic condition (PaCO(2) = 74. 9 +/- 14.3 mmHg), the baseline LCBF was about 46.5% higher than that under the normocapnic condition (PaCO(2) = 35.7 +/- 2.1 mmHg) (p < 0. 001), but after normalization for each baseline (divided by the prestimulus level), there was no significant difference in the peak value and the rise time of normalized evoked LCBF. On the other hand, the baseline level of LCBF under the hyperoxic condition (PaO(2) = 479.4 +/- 77.2 mmHg) was about 5.0% lower than that under the normoxic condition (PaO(2) = 105.5 +/- 7.8 mmHg) (p < 0.01), suggesting mild vasoconstriction under the condition of hyperoxia at rest. The peak value of normalized evoked LCBF under the hyperoxic condition was about 6.5% higher than that under the normoxic condition (p < 0.05). In addition, the rise time of evoked LCBF was earlier under the hyperoxic condition (0.37 +/- 0.16 s) than that under the normoxic condition (0.52 +/- 0.12 s) (p < 0.01). The field potential measured during stimulation under hypercapnic and hyperoxic conditions was not significantly different when compared with that under normal gas conditions. These results support our hypothesis and suggest that the excess oxygen is involved in the mechanism underlying the regulation of LCBF.

Hyperoxia-enhanced activation-induced hemodynamic response in human VI: an fMRI study.

The effect hyperoxia had on the hemodynamic response to visual stimulation (black and white checkerboard alternating at a frequency of 8 Hz) of human VI was investigated using a blood oxygenation level-dependent (BOLD) contrast with an fMRI technique. Data were acquired with a 5 on/5 off block paradigm using single-shot gradient-echo echo-planar imaging. Using a two-tailed paired t-test (p < 0.05, n = 13) it was found that the mean percentage signal change and the mean number of activated pixels was significantly increased for hyperoxia (5.7 +/- 0.9, 187 +/- 73, mean +/- SD) relative to those for normoxia (5.4 +/- 0.9, 168 +/- 58). We believe that these results indicate that hyperoxia enhances the activation-induced hemodynamic response in human VI.

Evoked local cerebral blood flow induced by somatosensory stimulation is proportional to the baseline flow.

The purpose of this study was to determine the relationship between the increase in local cerebral blood flow during neuronal activation (evoked LCBF) and the baseline flow level. We measured the hemodynamics in alpha-chloralose-anesthetized rats using laser-Doppler flowmetry during somatosensory stimulation under the hypocapnic, normocapnic and hypercapnic conditions. The baseline levels of LCBF and red blood cell (RBC) velocity under hypocapnia (PaCO(2)=26.4+/-1.1 mmHg) were, respectively, 10 and 11% lower than those under normocapnia (PaCO(2)=34.2+/-1.4 mmHg) (P<0.01). The evoked response magnitude of LCBF and RBC velocity under hypocapnia were, respectively, 22 and 18% lower than those under normocapnia. There was no significant difference in the baseline level and evoked response magnitude of RBC concentration. On the other hand, the baseline levels of LCBF, RBC velocity and RBC concentration under hypercapnia (PaCO(2)=73.4+/-13.3 mmHg) were, respectively, 47, 24 and 14% higher than those under normocapnia (PaCO(2)=34.7+/-2.5 mmHg) (P<0.01). The evoked response magnitude of LCBF, RBC velocity and RBC concentration under hypercapnia were, respectively, 96, 82 and 62% greater than those under normocapnia. After normalization with respect to each baseline level, there was no significant difference in normalized evoked response magnitude of LCBF, RBC velocity and RBC concentration, either between hypocapnic and normocapnic conditions or between hypercapnic and normocapnic conditions, indicating that evoked LCBF is proportional to the baseline flow. These results suggest that the amount of evoked LCBF is not determined by the demand for metabolic substrates.

Hemodynamics evoked by microelectrical direct stimulation in rat somatosensory cortex.

The aim of this study was to estimate the timing (latency) of the increase in red blood cell (RBC) velocity and RBC concentration, and the magnitude of response in local cerebral blood flow (LCBF) for neuronal activation. We measured LCBF change during activation of the somatosensory cortex by direct microelectrical stimulation. Electrical stimuli of 5, 10 and 50 Hz of 1 ms pulse with 10-15 microA, were given for 5 s. LCBF, RBC velocity and RBC concentration were monitored by laser-Doppler flowmetry (LDF) in alpha-chloralose anesthetized rats (n = 7). LCBF, RBC velocity and RBC concentration increased nearly proportionally to stimulus frequency, i.e. neuronal activity. LCBF rose approximately 0.5 s after the onset of stimulation, and there was no significant time lag of the latencies among LCBF, RBC velocity and RBC concentration at the same stimulus frequency. We interpret these results to mean that the onset of LCBF increase on cortical activation is reflected by a rapid change in arteriole (resistance vessel) dilation and capillary volume. The data also elucidate the linear relationship between LCBF increase and cortical activity.

CBF change evoked by somatosensory activation measured by laser-Doppler flowmetry: independent evaluation of RBC velocity and RBC concentration.

The purpose of this study was to examine the timing and magnitude of cerebral blood flow (CBF) responses to neuronal activation. We measured the changes in local CBF (LCBF), red blood cell (RBC) velocity and RBC concentration by laser-Doppler flowmetry (LDF) as well as field potential recordings during activation of the somatosensory cortex of the rat in response to electrical stimulation of the hind paw. Electrical stimuli, 0.1 ms pulses of 1-1.5 mA for 5 s, were applied at 0.2, 0.5, 5, 10 and 50 Hz under alpha-chloralose anesthesia. LCBF showed the maximum increase at 5 Hz, and rose approximately 0.5 s after the onset of stimulation regardless of the frequency. The maximum frequency of the field potentials was also obtained at 5 Hz. During activation of the somatosensory cortex, the onset of rise in RBC concentration did not precede that of RBC velocity, and the peak RBC concentration was noted earlier than that of both LCBF and RBC velocity, suggesting that both arteriolar diameter and active changes in the capillary contributed to the LCBF response.

Activation detection in functional MRI using subspace modeling and maximum likelihood estimation.

A statistical method for detecting activated pixels in functional MRI (fMIRI) data is presented. In this method, the fMRI time series measured at each pixel is modeled as the sum of a response signal which arises due to the experimentally controlled activation-baseline pattern, a nuisance component representing effects of no interest, and Gaussian white noise. For periodic activation-baseline patterns, the response signal is modeled by a truncated Fourier series with a known fundamental frequency but unknown Fourier coefficients. The nuisance subspace is assumed to be unknown. A maximum likelihood estimate is derived for the component of the nuisance subspace which is orthogonal to the response signal subspace. An estimate for the order of the nuisance subspace is obtained from an information theoretic criterion. A statistical test is derived and shown to be the uniformly most powerful (UMP) test invariant to a group of transformations which are natural to the hypothesis testing problem. The maximal invariant statistic used in this test has an F distribution. The theoretical F distribution under the null hypothesis strongly concurred with the experimental frequency distribution obtained by performing null experiments in which the subjects did not perform any activation task. Application of the theory to motor activation and visual stimulation fMRI studies is presented.

Speed of face recognition in humans: an event-related potentials study.

Event-related potentials (ERPs) were measured while subjects passively looked at a line drawing of a normal face or a line drawing in which parts of the face were scattered so as not to be recognized as a face (scattered face) in order to estimate the speed of face recognition in humans. Because the spatial frequencies of these two types of line drawings were very similar, one could minimize the potentials due to the structure coding stage of the face processing. In addition, passive viewing of these stimuli eliminates the contribution of other processing such as discrimination or memory retrieval. Comparing these two conditions, statistically significant positive potentials were observed in frontal areas from 135ms after stimulus onset for the normal face. These early positive differences were probably due to the face processing per se in human visual recognition. Although statistically significant differences were observed in frontal areas, these are probably related to fusiform or inferior temporal area activation that is often reported using neuro-imaging technologies such as PET or fMRI.

[Development of a high resolution beta camera].

We have developed and tested a high resolution beta camera. The beta camera consists of thin CaF2(Eu) scintillator, tapered fiber optics plate, position sensitive photomultiplier tube (PSPMT). The output of the PSPMT is fed to position calculation circuit and accumulated in the memory. The data in the memory is fed to personal computer for display and analysis. We have developed two types of beta cameras. One is 20 mm diameter field of view (FOV) camera, and the other is 10 mm diameter camera. Intrinsic spatial resolutions were 0.8 mm FWHM and 0.5 mm FWHM for 20 mm and 10 mm FOV camera, respectively. We confirmed that developed beta cameras may overcome the limitation of the resolution of the PET camera.

[Evaluation of reconstruction arc in myocardial SPECT imaging using a cardiac phantom--comparison between 360 degrees and 180 degrees arcs].

In order to investigate the effect of reconstruction arc on myocardial SPECT images, a series of phantom studies was performed with and without plastic chambers simulating perfusion defects using 201Tl and 99mTc. Coefficient of variations (CV) of the counts among the ROIs and defect contrast were evaluated in 360 degrees and 180 degrees images reconstructed from the same 360 degrees projection data. Reconstruction processes were identical for all images. In the absence of defects, the CV of the counts were approximately the same in 360 degrees and 180 degrees images. The CV of the counts in the 360 degrees 201Tl image, among 4 defects located on the anterior, lateral, inferoposterior, and septal walls, was superior to those in the 180 degrees images. In contrast, in the 99mTc images, the CV of the counts among the 4 defects in the 180 degrees image was superior to those of the 360 degrees image. The defect contrast was changed both by the location of the defect and by the reconstruction arc (201Tl, 99mTc). The defect contrast of the 180 degrees images, in both 201Tl and 99mTc experiments, was closer to the true contrast value as calculated by the count ratio between myocardium and defect. Although the defect contrast in the anterior, lateral and septal walls was more emphasized in the 180 degrees images, the defect contrast in the inferoposterior wall was less emphasized in the 180 degrees images compared to the 360 degrees (201Tl, 99mTc).

[Exposure to the technologists from radioactive patients during nuclear medicine studies].

In order to evaluate the exposure to the nuclear medicine technologists from patients who had been administrated with radiopharmaceuticals, we measured the exposure in 5 common diagnostic procedures (bone, lung, tumor scan, and brain, myocardial SPECT, n = 8 to 52) using a silicon semiconductor pocket dosimeter. We also measured the spatial dose rates at 5 cm, 50 cm, and 100 cm from skin surface of the patients (n = 10 to 21) using an ionization chamber, both 5 min after injection and right before the studies with the same procedures above. We further measured the spatial dose rate distributions around the patients in the 4 procedures (bone, renal, blood pool scan, and brain SPECT, n = 2 to 3). In results, the exposure to the technologists in each procedure was small (0.5, 0.5, 0.7, 1.6, and 0.3 muSv in each bone, lung, tumor scan, and brain, myocardial SPECT, respectively), compared with the dose limits of the medical workers. However, the dose-response relationships in cancer and hereditary effects, referred to as the stochastic effects, have been assumed linear and no threshold models; therefore, the exposure should be minimized. For this purpose, the measurements of spatial dose rates and spatial dose rate distributions were thought to be useful. The differences of these results among procedures were caused by the differences of dose distributions and physical and biological half lives of the radiopharmaceuticals. The results of the measurements in 7 consecutive weeks suggested that the direct measurement of the exposure using a high sensitive digital pocket dosimeter might result a reduced exposure to the technologists.

[Effect of reconstruction arc in myocardial SPECT imaging--comparison between 180 degrees and 360 degrees arc--].

A series of thallium-201 (201Tl) and technetium-99m (99mTc) myocardial perfusion images with or without perfusion defects were acquired by 360 degrees arc using a triple-head camera. The vertical long, horizontal long, and short axis images of 201Tl and 99mTc with 360 degrees, 180 degrees, and opposite 180 degrees were identically reconstructed and reoriented without attenuation correction. In order to detect the detailed differences between 360 degrees (30 degrees - 390 degrees) and 180 degrees (30 degrees - 210 degrees) images, the opposite 180 degrees (210 degrees - 30 degrees) images were utilized. Opposite 180 degrees images revealed the contribution of those to the 360 degrees images. In the normal perfusion images, the CV (coefficient of variation) of the counts in 360 degrees images with 201Tl by the segments was larger than 180 degrees images. On the contrary, the CV of the counts in 360 degrees images with 99mTc was smaller than 180 degrees images. This difference, caused by the difference of photon energy, were detected mainly as the extent of counts decreasing in the deep segments in the opposite 180 degrees images. Lesion contrasts of the opposite 180 degrees images were lower than those of 180 degrees images due to distance related collimator response (the detector response of the collimated gamma camera varies with source-to-detector distance) and scatter. Therefore, lesion contrasts were more decreased in the 360 degrees images compared with those of 180 degrees images, especially in the segments of lateral and anterior walls. The differences in lesion contrasts between 201Tl and 99mTc images were mainly in the segments of inferior and posterior walls (p < 0.05). Lesion contrast was dependent on the location of the perfusion defects, reconstruction arc, and photon energy.

[Comparison of inferior myocardial defect between planar and SPECT image of 123I-metaiodobenzylguanidine cardiac scintigraphy].

Discordant findings of inferior MIBG defect between SPECT and planar images were sometimes observed in the clinical studies. In this study, we compared inferior myocardial findings between planar and SPECT image of 123I-metaiodobenzyl-guanidine (MIBG) cardiac scintigraphy in 29 patients. All patients were estimated as normal in anterior accumulation of MIBG. The patients were divided into 3 groups according to the visual finding of inferior defect in the planar and SPECT image; normal group (normal inferior accumulation of MIBG both in the planar and SPECT image, N = 10), discordance group (inferior MIBG defect was only observed in the SPECT image, but was not observed in the planar image, N = 7), inferior defect group (inferior MIBG defect was observed both in the planar and SPECT image, N = 12). Inferior/anterior count ratio of SPECT and planar image were 0.96 +/- 0.11 vs. 0.97 +/- 0.05 in normal group, 0.59 +/- 0.21 vs. 0.99 +/- 0.13 in discordance group, 0.46 +/- 0.13 vs. 0.82 +/- 0.04 in inferior defect group. Liver/heart count ratio was significantly higher in the discordance group (2.07 +/- 0.49) than that in the normal (1.14 +/- 0.15) and inferior defect group (1.45 +/- 0.39). In phantom study, it has been reported that increased liver accumulation of MIBG causes artifactual inferior defect adjacent to the liver. These data indicate that increased liver/heart count ratio may cause artifactual inferior defect on MIBG SPECT image in the clinical studies. Planar image evaluation may be helpful to distinct the artifactual inferior defect on SPECT image.

[Initial myocardial uptake and myocardial clearance of 123I-metaiodobenzylguanidine in patients with ischemic heart disease of left ventricular dysfunction and dilated cardiomyopathy].

We studied initial myocardial uptake and myocardial clearance of 123I-metaiodobenzylguanidine (MIBG) in patients with ischemic heart disease of left ventricular dysfunction and dilated cardiomyopathy. Eleven patients with ischemic heart disease of left ventricular dysfunction (IHD group), 6 patients with dilated cardiomyopathy (DCM group) and 7 control cases (control group) were studied. Heart to mediastinum activity ratio (H/M) of early and delayed image was significantly lower in the IHD and DCM groups than in the control group. Although initial myocardial uptake of MIBG showed no significant difference among three groups, myocardial clearance of MIBG was significantly higher in the IHD (35 +/- 11%) and DCM (48 +/- 13%) groups than that in the control group (19 +/- 10%). H/M of delayed image was related to the left ventricular size, initial MIBG uptake and MIBG myocardial clearance. Negative correlation was observed between MIBG myocardial clearance and left ventricular ejection fraction in all cases. In conclusion, initial myocardial uptake of MIBG were not decreased in patients with IHD and DCM. Enhanced myocardial clearance of MIBG was observed not only in patients with DCM but also in patients with IHD.

[Artifactual defect of inferior myocardium on 123I-metaiodobenzylguanidine myocardial SPECT: characteristic findings and preventive method on phantom study].

Discordance between planar and SPECT image of inferior myocardial defect on 123I-metaiodobenzylguanidine myocardial scintigraphy (MIBG) was occasionally observed in the clinical studies. The purpose of this study is to clarify the existence of artifactual myocardial defect on MIBG SPECT image. Phantom study was performed in various kinds of situation using triple gamma camera. Artifactual defect adjacent to the liver was significantly observed in the case of increased liver/heart uptake ratio more than 2:1. Artifactual defect was markedly observed in the 180 degrees than that in the 360 degrees SPECT acquisition. To avoid artifactual defect during SPECT acquisition, liver phantom was moved down to the foot direction (vanishing liver position). In this phantom position, artifactual defect adjacent to the liver was not observed on reconstructed myocardial SPECT image. The vanishing liver position was also applicable to human study. Human body was inclined to right side at an angle of 15 degrees, artifactual defect could be avoided. Further study is needed to analyze the cause of this artifactual defect and to conform the preventive method with vanishing liver position in the routine myocardial SPECT examination.