Yukinori Katsumi

Enhanced lateral premotor activity during paradoxical gait in Parkinson's disease.

Parkinsons disease (PD) patients often show marked improvement of hypokinetic gait when exposed to special stimuli. To investigate physiological mechanisms underlying this “paradoxical gait” induced by visual cues in PD patients, we examined regional cerebral blood flow changes during gait on a treadmill guided by two different visual cues, the lines oriented transversely to the direction of walk (TL) and the lines parallel to it (PL). Ten PD patients and 10 age‐matched controls received injections of 99mTc‐hexamethylpropyleneamine oxime twice, once during each walking condition. Brain perfusion images were obtained by single‐photon emission computed tomography. When affected by TL, PD patients showed marked improvement of gait parameters, mainly reduction of cadence. In regional cerebral blood flow analysis, when TL was compared with PL, both groups had common activation in the posterior parietal cortex and cerebellar hemispheres. Especially in the right lateral premotor cortex, PD patients showed enhanced activation induced by TL to a significantly greater degree than the controls. The present study indicates that the network dedicated to visuomotor control, particularly the lateral premotor cortex, plays an important role in the development of the paradoxical gait induced by special visual stimuli in PD patients. Ann Neurol 1999;45:329–336

Age-related changes in cerebral blood flow activation during a Card Sorting Test

Abstract To determine the age-related changes in the neural processing involved in the Modified Card Sorting Test (MCST), we measured cerebral blood flow (CBF) during performance of the MCST and of the number-matching task in young and elderly subjects using positron emission tomography. Compared with that during the number-matching task, CBF during the MCST was increased in the left dorsolateral prefrontal cortex (DLPFC), left inferior parietal lobule, and left striate and prestriate cortices in both age groups. However, CBF activation in these areas was significantly lower in the elderly subjects than the young subjects. Furthermore, CBF activation was reduced in the left DLPFC, right parahippocampal gyrus, and prestriate cortex in proportion to the increase in the number of perseverative errors with aging. These results suggest that the impaired MCST performance in elderly subjects may be due, in part, to dysfunction of the network involving certain cortical areas such as the prefrontal and parahippocampal cortices, although the essential neural circuits for MCST performance were still preserved even in the elderly subjects.

Neural activity during attention shifts between object features

TO investigate the neural mechanisms involved in shifting attention we used positron emission tomography to examine regional cerebral blood flow (rCBF) during a task that demands shifting attention between color and shape. Significant activation was observed in the right dorsal prefrontal cortex and parieto-occipital cortex at all frequencies of attention shifts. The frequency of shifts between categories correlated significantly with rCBF in the rostral part of the supplementary motor area and the left precuneus, whereas the number of successive correct responses correlated with rCBF in the orbitofrontal cortex and the caudate nucleus. This study suggests that several prefrontal regions may participate in the processes of shifting attention in different ways.

Neuronal nitric oxide has a role as a perfusion regulator and a synaptic modulator in cerebellum but not in neocortex during somatosensory stimulation-An animal PET study

To clarify a role of neuronal nitric oxide in neurovascular coupling, we performed cerebral blood flow (CBF) and cerebral metabolic rate of glucose (CMR(glc)) measurements with positron emission tomography in somatosensory-stimulated cats using a specific neuronal nitric oxide synthase inhibitor, 7-nitroindazole (7-NI). The effect on flow-metabolism coupling were tested by global and regional-specific changes on CBF and CMR(glc), and the regional-specific effect was estimated both by regions of interest (ROI) and voxel-based (VB) analysis using globally-normalized CBF and CMR(glc) changes. The electrical somatosensory stimulation in the unilateral forepaw elicited coupled increase in CBF and CMR(glc) in the contralateral somatosensory cortex (7%) and the ipsilateral cerebellum (8%). 7-NI induced 20% decrease in global CBF both during rest and activation, but not in global CMR(glc) at simulation. Both ROI and VB analysis showed that 7-NI induced an increase in CMR(glc) (13%) in the ipsilateral cerebellum compared to control under vehicle alone, but it was accompanied by only 8% increase in CBF, suggesting uncoupling of flow-metabolism while it induced any perturbations in the contralateral somatosensory cortex. These observations suggest that neuronal nitric oxide has an important role for a mediator of regional neurovascular coupling as well as synaptic modulator in the cerebellum, but less so in the neocortex.

Cerebral Hematocrit Decreases With Hemodynamic Compromise in Carotid Artery Occlusion A PET Study

BACKGROUND AND PURPOSE This study investigated whether in patients with internal carotid artery occlusion the regional cerebral hematocrit correlates with cerebral hemodynamics or metabolic state and, if so, how the regional cerebral hematocrit changes in the hemodynamically compromised region. METHODS We used positron emission tomography to study seven patients with unilateral internal carotid artery occlusion and no cortical infarction in the chronic stage. The distributions of red blood cell and plasma volumes were assessed using oxygen-15-labeled carbon monoxide and copper-62-labeled human serum albumin-dithiosemicarbazone tracers, respectively. The calculated hematocrit value was compared with the hemodynamic and metabolic parameters measured with the oxygen-15 steady-state technique. RESULTS In the cerebral cortex, the value of the cerebral hematocrit varied but was correlated with the hemodynamic and metabolic status. Stepwise regression analysis revealed that the large vessel hematocrit, the cerebral metabolic rate of oxygen, and the cerebral blood flow or the oxygen extraction fraction accounted for a significant proportion of variance of the cerebral hematocrit. The oxygen extraction fraction and the cerebral metabolic rate of oxygen negatively correlated with the cerebral hematocrit, whereas the cerebral blood flow correlated positively: patients with reduced blood supply relative to metabolic demand (decreased blood flow with increased oxygen extraction fraction) showed low hematocrit values. CONCLUSIONS In carotid artery occlusion in the chronic stage, regional cerebral hematocrit may vary according to cerebral hemodynamics and metabolic status. Regional cerebral hematocrit may decrease with hemodynamic compromise unless oxygen metabolism concomitantly decreases.

Issues in measuring glucose metabolism of rat brain using PET: the effect of harderian glands on the frontal lobe.

We estimated the effect of the Harderian gland (an orbital gland of land vertebrates) on the measurement of cerebral metabolic rate of glucose (CMRGIc) of the rat brain using positron emission tomography (PET) for animal use. The Harderian gland had the high accumulation of 18-F labeled deoxyglucose (FDG) after intravenous injection. By placing the large regions of interest (ROI) (twice the full width at half maximum in diameter), the CMRGIc in the frontal region was slightly higher compared with the CMRGIc after Harderian gland resection, but the parietal and occipital regions and the cerebellum had the similar level of CMRGIc before and after Harderian gland resection. Therefore the Harderian gland has a slight effect on the frontal lobe CMRGIc, but such overestimation can be within the permissible range for PET study of rat brains.

Comparison of striatal dopamine D2 receptors in Parkinson's disease and progressive supranuclear palsy patients using 〔123I〕 iodobenzofuran single-photon emission computed tomography

Background and Purpose. To investigate the clinical applicability and validity of [123I] iodobenzofuran (IBF) single‐photon emission computed tomography (SPECT), the authors analyzed the changes in striatal dopamine D2 receptor binding among 7 patients with Parkinsons disease (PD), 6 patients with progressive supranuclear palsy (PSP) (Hoehn and Yahr stage II to IV), and 8 normal controls. Methods. SPECT data were acquired every 1 minute for 60 minutes postinjection of 167 MBq [123I] IBF. The binding potential (BP) of the striatum was evaluated by 2 methods: region‐of‐interest (ROI) analysis by the nonlinear least squares method using blood sampling and time‐series brain radioactivities in normal controls and a voxel‐by‐voxel method based on a region model that provided parametric images of BP without blood sampling. Results. Statistical parametric mapping indicated that BP in the striatum of PSP patients was significantly lower than that of PD patients and normal controls (P <.005, uncorrected), and there was no significant difference between PD patients and normal controls, even in patients with PD at an advanced stage. Data derived from the ROI method and a simplified reference region model showed good correlations in normal controls, indicating the validity of the latter model. Conclusions. The results predict that [123I] IBF SPECT, especially voxel‐by‐voxel BP parametric imaging, can discriminate among extrapyramidal diseases such as PD and PSP and may be applicable for clinical use.

Sensory stimulation accelerates dopamine release in the basal ganglia.

We report herein the modulation of dopamine release in the basal ganglia during peripheral electrical stimulation in animals. The endogenous dopamine release during electrical stimulation was measured in anesthetized cats by positron emission tomography (PET) using the D2 receptor agonist [11C]-raclopride. Binding potential (BP) parametric maps were calculated using a simplified reference region model. The regional dopamine release evoked by electrical stimulation was estimated both by region of interest (ROI) analysis and statistical parametric mapping (SPM 99). Both ROI analysis and statistical parametric mapping showed significant release of endogenous dopamine in the nucleus accumbens and the striatum contralateral to the stimulated side as compared to the resting condition as well as the ipsilateral side. Accordingly, we suggest that the activity of the dopaminergic neurons in the midbrain projecting to the nucleus accumbens and the striatum is modulated by the input from the afferent nerves. This provides an in vivo evidence for the importance of the basal ganglia in the processing of peripheral information required for normal movement. This may also explain the clinically observed sensory system abnormalities in patients with movement disorders.

Glucose metabolism in the rat frontal cortex recovered without the recovery of choline acetyltransferase activity after lesioning of the nucleus basalis magnocellularis.

We measured the cerebral metabolic rate of glucose (CMRglc) by using positron emission tomography (PET) with [18F]fluorodeoxyglucose (FDG) and the choline acetyltransferase (ChAT) activity at 3 days and 3 months after destruction of the nucleus basalis magnocellularis (NBM). Although the frontal ChAT activity remained 20% lower than that of controls even at 3 months post-lesioning, the frontal CMRglc, which was reduced by 40% at 3 days, returned to normal at 3 months, namely CMRglc recovered with time without the recovery of ChAT activity with time. Since glucose metabolism reflects mainly presynaptic neuronal activity, we speculate that presynaptic rearrangement may have some relation to the recovery of CMRglc.

Selective Cerebral Hematocrit Decrease in the Centrum Semiovale After Carotid Artery Occlusion: A PET Study

The centrum semiovale may be susceptible to hypoperfusion as a result of carotid artery occlusion. Recent studies suggest that the cerebral hematocrit decreases with diminished cerebral perfusion pressure. To investigate whether the effect of carotid artery occlusion on the hematocrit in the centrum semiovale is different from that in the cerebral cortex, seven patients with unilateral carotid artery occlusion were studied with positron emission tomography. The distributions of the red blood cell and plasma volumes were assessed using carbon monoxide labeled with oxygen 15 and human serum albumin-dithiosemicarbazone tracers labeled with copper 62, respectively. The CBF and CMRO2 were also measured with the 15O steady-state technique. The calculated values for the hematocrit in the centrum semiovale ipsilateral to the arterial occlusion were significantly decreased compared with those in any of the other regions examined (the overlying cortical region and the contralateral cortex and centrum semiovale). This decrease in hematocrit, which resulted from a more pronounced increase in plasma volume than in red blood cell volume, was associated with a decrease in CBF and an increase in the oxygen extraction fraction. Hemodynamic disturbance caused by carotid artery occlusion may induce selective decrease of hematocrit limited to the centrum semiovale.