Motohiro Kiyosawa

Auditory triggered mental imagery of shape involves visual association areas in early blind humans

Previous neuroimaging studies identified a large network of cortical areas involved in visual imagery in the human brain, which includes occipitotemporal and visual associative areas. Here we test whether the same processes can be elicited by tactile and auditory experiences in subjects who became blind early in life. Using positron emission tomography, regional cerebral blood flow was assessed in six right-handed early blind and six age-matched control volunteers during three conditions: resting state, passive listening to noise sounds, and mental imagery task (imagery of object shape) triggered by the sound of familiar objects. Activation foci were found in occipitotemporal and visual association areas, particularly in the left fusiform gyrus (Brodmann areas 19-37), during mental imagery of shape by both groups. Since shape imagery by early blind subjects does involve similar visual structures as controls at an adult age, it indicates their developmental crossmodal reorganization to allow perceptual representation in the absence of vision.

Baseline Features of Idiopathic Optic Neuritis as Determined by a Multicenter Treatment Trial in Japan

BACKGROUND An optic neuritis treatment trial was conducted at 30 clinical centers in Japan using the same protocol. Patient participation was based on: age range of 14-55 years; acute symptoms indicative of unilateral optic neuritis of unknown or demyelinating origin; visual symptoms of 14-day duration or less; relative afferent pupillary defect in affected eye; and normal or swollen optic disc of affected eye. CASES Initially, 102 patients qualified for participation; baseline data were obtained for analysis from 70 of these patients. Demographic characteristics of Japanese patients with optic neuritis were clarified and compared with those in a US study. OBSERVATIONS The incidence of ocular or periocular pain and the presence of periventricular plaques were noted to be lower, and the incidence of disc swelling higher, in the Japanese patients, suggesting racial differences in the characteristics of the disease. Such differences may possibly be related to the lower incidence of multiple sclerosis in Japanese patients. The results of visual function tests were virtually the same in both studies. The nonaffected eyes of more than half the patients showed abnormal mean deviation in Humphrey field analysis, as also noted in the US study. CONCLUSIONS The baseline clinical features of optic neuritis in the Japanese patients have been defined. Some racial differences in the characteristics of the disease may exist.

Multicenter Clinical Trial for Evaluating Methylprednisolone Pulse Treatment of Idiopathic Optic Neuritis in Japan

BACKGROUND A randomized, controlled clinical trial was conducted in 1991 to compare an intravenous megadose of methylprednisolone with a control drug (mecobalamin) for treating acute idiopathic optic neuritis. CASES Sixty-six cases from 22 clinical centers throughout Japan were examined to evaluate the treatment on visual function parameters, such as visual acuity, visual field, color vision, contrast sensitivity, and critical flicker frequency. OBSERVATIONS The methylprednisolone pulse treatment group showed faster recovery of visual function, particularly the visual acuity at 1 week (P<.05), Humphrey field analyzer mean deviation at 3 weeks (P<.05), and color vision at 1 week (P<.05). Recovery of contrast sensitivity at several different spatial frequencies was significant in the pulse treatment group at 1 (P<.01), 2 (P<.05), and 4 weeks (P<.05) after the start of treatment. Visual function test results at 12 weeks and 1 year were essentially the same in the two treatment groups. Side effects appeared more frequently in the pulse treatment group than in the control (P<.05). CONCLUSIONS Pulse treatment does not appear effective for idiopathic optic neuritis even though visual function in the pulse treatment group of this trial recovered more quickly during the initial phase compared to the controls. More effective and specific treatment should be established for optic neuritis.

Evaluation of carbon-11 labeled KF15372 and its ethyl and methyl derivatives as a potential CNS adenosine A1 receptor ligand.

We prepared [11C]KF15372 ([1-propyl-11C]8-dicyclopropylmethyl-1,3-dipropylxanthine, refs 10, 13) as well as its 11C-ethyl and 11C-methyl derivatives ([11C]EPDX and [11C]MPDX), and examined the potential of the three compounds as PET ligands for CNS adenosine A1 receptors. The three compounds had high affinity for the A1 receptors in vitro in the following order; [11C]EPDX > [11C]KF15372 > [11C]MPDX. In mice, the highest initial brain uptake was found in [11C]MPDX followed by [11C]EPDX and [11C]KF15372, but the level of [11C]MPDX decreased faster than those of the other two compounds. The uptake of each compound was decreased by carrier KF15372, but not by an A2A antagonist, indicating the selective affinity for the A1 receptors. Autoradiography with [11C]MPDX ex vivo demonstrated decreased A1 receptor binding in the superior colliculus of rats deprived of retino-collicular fibers by contralateral eye enucleation. These results show that three compounds have potential as PET ligands for CNS adenosine A1 receptors.

Functional neuroanatomy of visual object naming: a PET study

Abstract⊎ Background: The ability to name objects depends partly on visual perception. We used positron emission tomography (PET) to measure activity-related changes in regional cerebral blood flow (r-CBF) in order to identify regions of the brain activated during visual object naming. ⊎ Methods: Four right-handed volunteers were recruited. Following an intravenous injection of15O-labeled water, r-CBF was measured during visual object naming, counting numbers, and resting. PET and MRI images were coregistered, the size of the brain was proportionally adjusted in each axis to Talairachs and Tournouxs atlas, and the comparison of stimulated versus resting blood flow images revealed activated brain regions. ⊎ Results: In the subtraction of resting from naming, activation was observed in the bilateral primary visual cortex, bilateral fusiform gyrus, left lingual gyrus, bilateral inferotemporal cortex, bilateral inferior frontal gyrus, bilateral precentral gyrus, anterior cingulate gyrus, left parietal operculum, and left putamen. In the subtraction of counting from naming, most of the those areas were activated, but no significant activity was observed in the left lingual gyrus, left parietal operculum, or bilateral precentral gyrus (motor cortex). The areas activated with the paradigm included those dedicated to visual perception (primary and associate visual cortex), visual recognition (inferior temporal cortex), and phonological output (Brocas area). ⊎ Conclusion: Our results indicated that the major neural network from occipital lobe to frontal cortex, which is mainly involved in the ventral visual pathway, demonstrated activation in these tasks. Result of this study will serve as base line data for analyzing the findings in patients with impaired visual perception.

Carbon-11-labeled KF21213: a highly selective ligand for mapping CNS adenosine A2A receptors with positron emission tomography

In vivo assessment of the adenosine A(2A) receptors localized in the striatum with positron emission tomography (PET) may offers us a new diagnostic tool for neurological disorders. We evaluated the potential of [7-methyl-(11)C](E)-8-(2,3-dimethyl-4-methoxystyryl)-1, 3,7-trimethylxanthine ([(11)C]KF21213) as a PET ligand for mapping adenosine A(2A) receptors in the central nervous system. KF21213 showed a high affinity for the adenosine A(2A) receptors in vitro (Ki = 3.0 nM) and a very low affinity for the A(1) receptors (Ki > 10,000 nM). In mice, the striatal uptake of [(11)C]KF21213 increased for the first 15 min and then gradually decreased, whereas the uptake in the reference regions such as the cortex and cerebellum rapidly decreased. The uptake ratio of striatum to cortex and striatum to cerebellum increased to 8.6 and 10.5, respectively, at 60 min postinjection. The striatal uptake was significantly blocked by co-injection of carrier KF21213 or each of three other A(2A) antagonists, but not by co-injection of A(1) antagonist. The specific uptake was not detected in the cortex or in the cerebellum. Ex vivo autoradiography and PET clearly visualized adenosine A(2A) receptors in the rat striatum. [(11)C]KF21213 was the most selective tracer for mapping adenosine A(2A) in the central nervous system by PET among the tracers proposed to date.

Glucose hypermetabolism in the thalamusof patients with essential blepharospasm

AbstractEssential blepharospasm (EB) is classified as a form of focal dystonia characterized by involuntary spasms of the musculature of the upper face. The basic neurological process causing EB is not known. The purpose of this study was to investigate cerebral glucose metabolism in patients with EB whose symptoms were suppressed by an injection of botulinum-A toxin. Earlier studies were confounded by sensory feedback activities derived from dystonic symptom itself. Cerebral glucose metabolism was examined by positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in 25 patients (8 men and 17 women; age 52.6 ± 10.1 years) with EB. The patients were awake but with the spasms suppressed by an injection of botulinum-A toxin. Thirty-eight normal volunteers (14 men and 24 women; age 58.2 ± 7.3 years) were examined as controls. The difference between the two groups was examined by statistical parametric mapping (SPM99). A significant increase in the glucose metabolism was detected in the thalamus and pons in the EB patients. Hyperactivity in the thalamus may be a key pathophysiological change common to EB and other types of focal dystonia. The activity of the striatum and cerebellum are likely to be sensory dependent.

Ophthalmological findings in patients with Takayasu disease

We examined 65 (61 female and 4 male) Takayasu patients. Patient age ranged from 17 to 78 years old (mean 50.2); age of onset was from 11 to 60 years old (mean 32.8); and duration from onset to referral ranged from 1 month to 43 years (mean 16.8 years). Routine ophthalmological examinations were performed. Fluorescein angiography, kinetic perimetry by Goldmann perimetry, static perimetry by Octopus 1-2-3, electroretinography (ERG), and measurements of central retinal arterial pressure were also performed, as appropriate. Major causes of impaired visual acuity (less than 16/20) were cataract. A few patients had low visual acuity caused by Takayasu disease itself. On the other hand, although not many complained of visual disturbance, about 35% of patients had subnormal visual functions. Because the visual deterioration may be based on ocular hypoperfusion, which may subsequently lead to more serious changes, regular ophthalmological examination for every Takayasu disease patient is recommended.

Decreased dopamine D2 receptor binding in essential blepharospasm

Objectives –  The purpose of this study was to investigate whether dopamine D2 receptor binding was altered in the striatum of essential blepharospasm patients.

Cortical hypometabolism and its recovery following nucleus basalis lesions in baboons: a PET study

The cerebral metabolic rate for glucose was measured serially with positron emission tomography and [18F]fluorodeoxyglucose in five baboons with stereotactic electrocoagulation of the left nucleus basalis of Meynert (NbM). Four days after lesion, a significant metabolic depression was present in the ipsilateral cerebral cortex, most marked in the frontotemporal region, and which recovered progressively within 6–13 weeks. These data demonstrate that adaptive mechanisms efficiently compensate for the cortical metabolic effects of NbM-lesion-induced cholinergic deafferentation. Moreover, unilateral NbM lesions also induced a transient reduction in contralateral cortical metabolic rate, the mechanisms of which are discussed. Explanation of these effects of cholinergic deafferentation in the primate could further our understanding of the metabolic deficits observed in dementia of the Alzheimers type.