Tomoya Yamamoto

Cyclooxygenase 2 is a key enzyme for inflammatory cytokine-induced angiogenesis

Cyclooxygenasel (COX1) and COX2 mediate the rate‐limiting step in arachidonic acid me¬tabolism. Expression of COX2 mRNA and protein is often enhanced in various human cell types by inflam¬matory cytokines such as interleukin‐1β (IL‐1β) and tumor necrosis factor α (TNFα). IL‐1β enhanced ex¬pression of various prostanoids and this expression was blocked by COX2 selective inhibitors. IL‐1β markedly induced angiogenesis in vitro and in vivo, which was significantly inhibited by COX2 selective inhibitors but not by a vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor. In contrast, COX2 selective inhibitors only partially blocked VEGF‐induced angiogenesis. EP2, EP4 (prostaglandin E2 recep¬tors) agonists and thromboxane A2 (TXA2) receptor agonists induced angiogenesis in vitro and in vivo; IL‐1β‐induced angiogenesis was blocked by an EP4 antagonist and a TXA2 receptor antagonist. IL‐1β in¬duced much less angiogenesis in cornea of COX2 knockout mice than that of wild‐type mice. This is the first report that COX2 and some prostanoids play a key role in IL‐1β‐induced angiogenesis.—Kuwano, T., Nakao, S., Yamamoto, H., Tsuneyoshi, M., Yamamoto, T., Kuwano, M., Ono, M. Cyclooxygenase 2 is a keyenzyme for inflammatory cytokine‐induced angiogenesis. FASEB J. 18, 300–310 (2004)

Comparison of magnetoencephalography, functional MRI, and motor evoked potentials in the localization of the sensory-motor cortex.

To clarify the topographical relationship between peri-Rolandic lesions and the central sulcus, we carried out presurgical functional mapping by using magnetoencephalography (MEG), functional magnetic resonance imaging (f-MRI), and motor evoked potentials (MEPs) on 5 patients. The sensory cortex was identified by somatosensory evoked magnetic fields using MEG (magnetic source imaging (MSI)). The motor area of the hand region was identified using f-MRI, during a hand squeezing task. In addition, transcranial magnetic stimulation localized the hand motor area on the scalp, which was mapped onto the MRI. In all cases, the sensory cortex was easily identified by MSI and the results of MSI correlated well with the findings obtained by the intraoperative recording of somatosensory evoked potentials. In contrast, the motor cortex could not be localized by f-MRI due to either the activated signal of the large cortical vein or the lack of any functional activation in the area of peri-lesional edema. MEPs were also unable to localize the entire motor strip. Therefore, at present, MSI is considered to be the most reliable method to localize peri-Rolandic lesions [corrected].

Visual evoked cortical magnetic responses to checkerboard pattern reversal stimulation: A study on the neural generators of N75, P100 and N145

In an attempt to elucidate the neural generators of pattern reversal visual evoked potentials (PR-VEPs), we measured the visual evoked magnetic fields (PR-VEFs) using a 37-channel magnetoencephalography in six healthy young adults. A half-field checkerboard pattern was phase-reversed at a rate of 1 Hz to stimulate the right or left visual half-field, thus yielding 12 PR-VEFs in total from the six subjects. The simultaneously recorded scalp PR-VEPs showed three distinct components of N75, P100 and N145. Three corresponding components were also identified in the PR-VEFs with similar peak latencies (N75m, P100m and N145m). P100m and N145m were clearly identified in all 12 PR-VEFs, whereas N75m was observed in only nine of 12 PR-VEFs. The equivalent current dipoles (ECDs) of N75m, P100m and N145m were located closely to each other in the occipital cortex around the calcarine fissure contralateral to the stimulated visual field, when they were overlaid on the MRI. The reliability of dipole estimation was highest in P100m, followed by N145m while N75m showed the least reliability. The direction of the current flow of ECDs of N75m and N145m was from the medial to the lateral in the occipital cortex when viewed in a coronal section, whereas that for P100m was toward the medial. The ECD location of P100m changed according to the retinotopic organization when the upper or lower quadrant of the visual field was stimulated, with the ECDs being located in the lower or upper part, respectively, of the visual cortex. Our results therefore indicate that the neural origins of N75m, P100m and N145m of PR-VEFs are in the primary visual cortex on the contralateral side of the stimulated visual half-field, while the three components are physiologically distinct.

Feeding-related activity of glucose-and morphine-sensitive neurons in the monkey amygdala

Feeding-related neuronal activity of monkey amygdalar glucose-sensitive and morphine-sensitive cells was investigated during a task that required bar-pressing to obtain food. Both glucose-sensitive and morphine-sensitive cells, located mostly in the centromedial part of the amygdala, decreased firing during the bar-press period more often than insensitive cells. Naloxone attenuated the decrease in activity during the bar press period. The results suggest involvement of these glucose- and morphine-sensitive cells in the control of food acquisition behavior.

Functional mapping of the sensorimotor cortex: combined use of magnetoencephalography, functional MRI, and motor evoked potentials

Combined use of magnetoencephalography (MEG), functional magnetic resonance imaging (f-MRI), and motor evoked potentials (MEPs) was carried out on one patient in an attempt to localise precisely a structural lesion to the central sulcus. A small cyst in the right frontoparietal region was thought to be the cause of generalised seizures in an otherwise asymptomatic woman. First the primary sensory cortex was identified with magnetic source imaging (MSI) of somatosensory evoked magnetic fields using MEG and MRI. Second, the motor area of the hand was identified using f-MRI during handsqueezing. Then transcranial magnetic stimulation localised the hand motor area on the scalp, which was mapped onto the MRI. There was a good agreement between MSI, f-MRI and MEP as to the location of the sensorimotor cortex and its relationship to the lesion. Multimodality mapping techniques may thus prove useful in the precise localisation of cortical lesions, and in the preoperative determination of the best treatment for peri-rolandic lesions.

The effect of interstimulus intervals and between-block rests on the auditory evoked potential and magnetic field: is the auditory P50 in humans an overlapping potential?

OBJECTIVE The human auditory P50 may consist of overlapping potentials. To test this hypothesis, we manipulated interstimulus intervals (ISIs) and between-block rests, and recorded the P50, P50m, N100 and the N100m simultaneously. METHODS Subjects were 12 right-handed healthy adults. Four conditions included: (1) 1.5 s/rest, (2) 1.5 s/successive, (3) 0.5 s/rest, and (4) 0.5 s/successive. Auditory stimuli were presented a total of 880 times for each condition. Auditory evoked potentials and magnetic fields were recorded. We examined the P50, N100, P50m, N100m and dipoles of the P50m and the N100m. RESULTS There was no significant effect of the ISI on the P50 amplitudes, but the P50m amplitudes in the 0.5 s ISI conditions were significantly smaller than those in the 1.5 s ISI conditions. The N100 and the N100m amplitudes in the 0.5 s ISI conditions were significantly smaller than those in the 1.5 s ISI conditions. The N100 and the N100m amplitudes in the resting conditions were significantly larger than those in the successive conditions. The P50m dipoles were slightly deeper and more anterior than those of the N100m in primary auditory cortex. CONCLUSIONS Central structures other than supratemporal cortex contribute to the P50 and that the P50 in humans represents overlapping potentials.

Differential interaction of somatosensory inputs in the human primary sensory cortex: a magnetoencephalographic study

OBJECTIVE Somatosensory evoked magnetic fields (SEFs) were recorded to investigate the interaction of the somatosensory inputs using the modality of electrical finger stimulation in 6 normal subjects. METHODS Electrical stimuli were given to the index (II), middle (III) or little (V) fingers individually, and also to pairs of either the II and III simultaneously, or the II and V simultaneously. The interaction ratio (IR) was calculated as the ratio of the SEF amplitude by simultaneous two-finger stimulation to the arithmetically summed SEF amplitudes of two individual-finger stimulations. RESULTS SEFs showed 3 major components: N22m, P30m and P60m. The N22m and P60m revealed a clear somatotopic organization in the primary sensory cortex (S1) in the sequence of II, III and V, while the P30m showed a cluster with medial location compared with N22m and P60m in S1. The N22m had a significantly greater IR in II and III stimulation compared to that in II and V stimulation. The P60m also showed a similar trend in the IR but was greater than that of N22m. In contrast, the IR in P30m showed no such tendency. CONCLUSION The interaction of S1 was most influenced when adjacent receptive fields were activated in the modality of electrical finger stimulation. Our results were consistent with the concept that the Brodmanns areas in S1 which produce the 3 components of the SEFs have different functional organization.

Tonotopic organization of human auditory cortex revealed by multi-channel SQUID system

A 14-channel SQUID (superconducting quantum interference device) system has been used to record the magnetic signal from the human brain in response to an auditory stimuli (750, 1,000, 1,250 and 1,500 Hz, 70, 76 and 82 dB SPL, 500 ms duration). Three individuals with normal hearing were studied. The locations of magnetic response at the latency of 70 ms (P70), 100 ms (N100) and 160 ms (P160) from the onset of the auditory stimulus were identified. The location for N100 response corresponded to the primary auditory cortex (area 41), where a clear tonotopic organization was demonstrated. The amplitopic organization was less evident. These results suggest a flow of auditory signals in the temporal lobe and tonotopic organization in the auditory cortex.

The isochronic band hypothesis and climbing fibre regulation of motricity: an experimental study

The dynamic organization of the olivocerebellar afferent input to Purkinje cells was examined in rat cerebellar cortex. The distribution of synchronous Purkinje cell complex spike activity was characterized, bilaterally, utilizing multiple electrode recordings in crus IIa folium under ketamine anaesthesia. The results confirmed the existence of rostrocaudal complex spike isochronicity bands with a mediolateral width of 500 µm. For a given band, no finer spatial submicrostructures could be discerned at a first‐order approximation (two‐dimensional projection). Closer analysis determined that isochronicity between bands is not continuous in space but demonstrates discrete discontinuities at the mediolateral boundaries. Principal component multivariate analysis revealed that the first principal component of the spatio‐temporal variance is synchronicity along the rostrocaudal band with a decreased level of coupling in the mediolateral direction at the band boundary. Furthermore, this discrete banding isochronicity is organized by the distribution of feedback inhibition from the cerebellar nuclei on to the inferior olive nucleus. The usual multiple band structure can be dynamically altered to a single wide‐band dynamic architecture, or to other patterns of activity, as may be required by movement coordination.

Presurgical three-dimensional magnetic source imaging of the somatosensory cortex in a patient with a peri-Rolandic lesion: technical note.

We report a case in which three-dimensional (3-D) magnetic source imaging, using the combined techniques of magnetoencephalography and 3-D magnetic resonance imaging, was employed to localize precisely a structural lesion in the precentral gyrus. The lesion was primarily a hematoma located in the right frontal lobe and was associated with a cryptic arteriovenous malformation that had produced repeated seizures with progressive left hemiparesis. 3-D magnetic source imaging mapped the entire somatosensory homunculus and localized the hematoma in the precentral gyrus. Both this relationship and the deduced localization were confirmed by a cortical recording of somatosensory evoked potentials at the time of surgery. 3-D magnetic source imaging proved to be useful in localizing cortical lesions precisely and in determining preoperatively the best form of treatment for the peri-Rolandic lesions.