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Biomedical subjects

N Sadato

Publications and source records attributed to N Sadato.

At least 19 recordsLinked to original sources

Complexity affects regional cerebral blood flow change during sequential finger movements.

Brain regions activated with complex sequential finger movements were localized by measuring regional cerebral blood flow (rCBF) with positron emission tomography. Whereas the total number and frequency of finger movements were kept constant, the complexity of auditory cued sequential finger movements of the right hand varied, with sequence length as the independent variable. In four conditions of differing complexity, the bilateral primary sensorimotor area, left ventral premotor cortex, posterior supplementary motor area, right superior part of the cerebellum, and left putamen were consistently and equally activated. This finding suggests an executive role in running sequences, regardless of their length. The right dorsal premotor cortex (Brodmann area 6) and the right precuneus (Brodmann area 7) showed a linear increase of rCBF as sequence complexity increased. This finding is consistent with the hypothesis that these areas function in the storage of motor sequences in spatial working memory and the production of ongoing sequential movement with reference to that of buffered memory. A similar increase in the cerebellar vermis and the left thalamus likewise suggests a role of these subcortical structures in complexity of sequential finger movements. Conversely, the left inferior parietal lobule showed a decrease of rCBF as complexity increased. Because short-term phonological storage is localized to this area, we suggest that the visuospatial working memory system may suppress other systems not in use. Our findings suggest that complex sequential finger movements recruit a discrete set of brain areas, in addition to areas underlying the execution of simple movement sequences.

Adult

Activation of the primary visual cortex by Braille reading in blind subjects.

Primary visual cortex receives visual input from the eyes through the lateral geniculate nuclei, but is not known to receive input from other sensory modalities. Its level of activity, both at rest and during auditory or tactile tasks, is higher in blind subjects than in normal controls, suggesting that it can subserve nonvisual functions; however, a direct effect of non-visual tasks on activation has not been demonstrated. To determine whether the visual cortex receives input from the somatosensory system we used positron emission tomography (PET) to measure activation during tactile discrimination tasks in normal subjects and in Braille readers blinded in early life. Blind subjects showed activation of primary and secondary visual cortical areas during tactile tasks, whereas normal controls showed deactivation. A simple tactile stimulus that did not require discrimination produced no activation of visual areas in either group. Thus in blind subjects, cortical areas normally reserved for vision may be activated by other sensory modalities.

Blindness

Brain activation during script event processing.

Regional cerebral blood flow was measured with positron emission tomography in seven normal volunteers while they performed various script event verification tasks. The left frontal lobe, left anterior cingulate and the anterior part of the left superior temporal gyrus were more activated in the script event membership and action categorization conditions, whereas the right frontal lobe, left superior temporal gyrus and the middle temporal gyrus bilaterally were more activated in the script event temporal order verification condition. These results indicate that the temporal ordering of script events and determining whether an event belongs to a particular script or action category are processed by distinctive distributed neuronal networks.

Adult

Simplified quantification of regional cerebral blood flow with 99mTc-ECD SPECT and continuous arterial blood sampling.

The goal of this study was to develop a simple method for quantification of regional cerebral blood flow (rCBF) with 99mTc-ethyl cysteinate dimer (ECD) SPECT. Following an intravenous constant infusion of ECD for one minute, serial dynamic SPECT imaging was performed for 40 minutes in 6 healthy male volunteers with intermittent arterial blood sampling. PET scan with 15O-water was performed on the same day before the SPECT study for measurement of rCBF. Arterial blood data demonstrated rapid conversion of ECD to the hydrophilic metabolites, and most of the arterial input to the brain was completed within 5 minutes after the injection. Brain activity reached a peak value soon after the cessation of infusion, and was stable thereafter with very little washout. Net extraction of ECD in the brain calculated by arterial input of ECD and rCBF demonstrated a rapid decrease within a few minutes, reaching 42.7% at 5 minutes. The simulation study suggested that the arterial blood activity obtained by continuous drawing for 5 minutes and a single SPECT scan would provide a reasonable estimate of rCBF under the assumption of constant net extraction in the brain.

Adult

Cochlear implant efficiency in pre- and postlingually deaf subjects. A study with H2(15)O and PET.

We used 15O-labelled water in a PET study to test the efficiency of cochlear implants (CIs) in transmitting auditory information to the brain in 10 profoundly deaf subjects. Five were postlingually deaf, and five were prelingually deaf. All the subjects were right-handed. White noise and verbal stimuli, delivered through the CIs, were used for cortical activation. Similar tasks were performed by six right-handed hearing subjects as a control group. In the postlingually deaf subjects, verbal stimulation activated the transverse temporal gyri (primary auditory cortices) mainly on the side contralateral to the CI. The left posterior superior temporal gyrus (Wernicke's area), and the left inferior frontal gyrus (Broca's area) were also activated irrespective of stimulated side. The location of these activated foci was the same as that of the control group. White noise stimulation led to an increase of regional cerebral blood flow (rCBF) only in the primary auditory cortices of the postlingually deaf subjects, only on the side contralateral to the CI, and the intensity of activation was less than that obtained with verbal stimulation. In the prelingually deaf subjects, Wernicke's area and Broca's area were significantly activated by verbal stimulation, whereas there was no activation in the primary auditory cortices. White noise did not activate the primary auditory cortex in the prelingually subjects. These findings suggest that cortical representation of language is not dependent on early auditory experience, while processing in the primary auditory cortices is experience-dependent. The postlingually deaf subjects had a greater increase of rCBF in the Broca's and Wernicke's areas and better sentence comprehension than the prelingually deaf subjects, which suggest a parallel relation between rCBF increase and the ability to recognize spoken language. H2(15)O-PET with auditory stimulation is an effective means of objectively quantifying the response of auditory and association cortices after CIs in deaf subjects.

Adolescent

Frequency-dependent changes of regional cerebral blood flow during finger movements.

To study the effect of the repetition rate of a simple movement on the distribution and magnitude of neuronal recruitment, we measured regional CBF (rCBF) in eight normal volunteers, using positron emission tomography and 15O-labeled water. An auditory-cued, repetitive flexion movement of the right index finger against the thumb was performed at very slow (0.25 and 0.5 Hz), slow (0.75 and 1 Hz), fast (2 and 2.5 Hz), and very fast (3 and 4 Hz) rates. The increase of rCBF during movement relative to the resting condition was calculated for each pair of movement conditions. Left primary sensorimotor cortex showed no significant activation at the very slow rates. There was a rapid rise of rCBF between the slow and the fast rates, but no further increase at the very fast rates. The right cerebellum showed similar changes. Changes in the left primary sensorimotor cortex and the cerebellum likely reflect the effect of the movement rate. The posterior supplementary motor area (SMA) showed its highest activation at the very slow rates but no significant activation at the very fast rates. Changes correlating with those in the SMA were found in the anterior cingulate gyrus, right prefrontal area, and right thalamus. The decreases in CBF may reflect a progressive change in performance from reactive to predictive.

Adult

Cerebral structures participating in motor preparation in humans: a positron emission tomography study.

1. Using positron emission tomography and measurement of regional cerebral blood flow (rCBF) as an index of cerebral activity we investigated the central processing of motor preparation in 13 healthy volunteers. 2. We used a motor reaction time paradigm with visual cues as preparatory and response signals. A preparatory stimulus (PS) provided either full, partial, or no information regarding two variables of a forthcoming right finger movement: finger type (index or little finger) and movement direction (abduction or elevation). After a variable delay period, a response stimulus (RS) prompted the movement. A condition was also tested in which the subject could freely select any of the four possible movements during the preparation period ("free" condition). The timing of events was designed to emphasize the motor preparation phase over the motor execution component during the scanning time of 1 min. 3. Distinct preparatory processes, which depended on the information contained in the PS, were demonstrated by significant differences in reaction time between conditions. The reaction time was shorter in the "full" and free conditions, intermediate in the two partial information conditions ("finger" and "direction"), and longer when no preparatory information was available ("none" condition). Conversely, movement time and movement amplitude were similar between conditions, establishing the constancy of the motor executive output. 4. In comparison with a "rest" condition, which had matched visual inputs, the different conditions of motor preparation were associated with increased rCBF in a common set of cerebral regions: the contralateral frontal cortex (sensorimotor, premotor, cingulate, and supplementary motor cortex), the contralateral parietal association cortex (anterior and posterior regions), the ipsilateral cerebellum, the contralateral basal ganglia, and the thalamus. This observation substantiates the participation of those cerebral structures in the preparation for movement. Furthermore, the similarity of the activated areas among the different conditions compared with the rest condition suggests a single anatomic substrate for motor preparation, independent of the movement information context. 5. Differing amounts of movement information contained in the PS affected rCBF changes in some cerebral regions. In particular, the rCBF in the anterior parietal cortex (Brodmann's area 40) was significantly larger in each of the full, finger, and direction conditions, individually, compared with the none condition. This observation supports the hypothesis that the anterior parietal association cortex plays a major role in the use of visual instructions contained in the PS for partial or complete preparation to perform a motor act. On the other hand, the posterior parietal association cortex (Brodmann's area 7) was more activated in the finger, direction, and none conditions than in the full condition. This increased activity with restricted advance information suggests that the posterior region of the parietal cortex is concerned with correct movement selection on the basis of enhanced spatial attention to the RS. 6. In contrast with the parietal cortex, the secondary motor areas (i.e, premotor cortex, cingulate cortex, and supplementary motor area) showed similar activity regardless of the degree of preparation allowed by the advance visual information. Thus the parietal cortex may play a more crucial role than the secondary motor areas in integrating visual information in preparation for movement. 7. The effect on brain activity of the internal (self-generated) versus the external (cued) mode of movement selection was assessed by comparing the free and full conditions, the preparatory component being matched in the two conditions. The anterior part of the supplementary motor area was the main area preferentially involved in the internal selection of movement, independently of motor preparation processes.

Adult

Nonlinearity correction of brain perfusion SPECT based on permeability-surface area product model.

UNLABELLED: It is well known that many cerebral perfusion tracers underestimate cerebral blood flow in high flow range. A model has been proposed to correct nonlinear relationship of flow and uptake of the tracers that accounts for the permeability-surface area product (PS model). METHODS: We examined 43 patients in this study. To test the feasibility of this method for 123I-IMP, 99(m)Tc-HMPAO and 99(m)Tc-ECD, radioactivity ratios of cerebral regions to cerebellum (C/Cr) on SPECT images were compared with those of rCBF (F/Fr) measured by PET using the 15O CO2 steady-state method. Coefficient for correction in the PS model was estimated by the least squares method, and SPECT data were corrected using these coefficients. RESULTS: Estimated PS value by this method was highest in IMP (116 ml/min/100 g) followed by ECD (66 ml/min/100 g) and HMPAO (46 ml/min/100 g). The corrected SPECT data demonstrated an excellent linear relationship, which was close to unity, with rCBF. CONCLUSION: These results indicate that the PS model can be used for nonlinearity correction of brain perfusion SPECT.

Adult

Modeling other minds.

Nine normal volunteers performed a 'theory of mind' task while their regional brain blood flow pattern was recorded using the PET [15O]H2O technique. Control conditions induced subjects to attend to the visual and semantic attributes of known objects. In a third condition, subjects had to infer the function of an unfamiliar object from its form. In the 'theory of mind' condition, subjects had to infer function based on the form of both familiar and unfamiliar objects and in addition, model the knowledge and rationality of another mind about the function of these objects. Performance during the 'theory of mind' condition evoked the activation of a distributed set of neural networks with prominent activation of the left medial frontal lobe (Brodmann area 9) and left temporal lobe (Brodmann areas 21, 39/19, 38). This result suggests that when inferential reasoning depends on constructing a mental model about the beliefs and intentions of others, the participation of the prefrontal cortex is required. When access to such knowledge is affected by central nervous system dysfunction, such as that found in autism, modeling other minds may prove difficult.

Adolescent

Brain activation during the generation of non-emotional and emotional plans.

We studied 12 normal volunteers who were asked to imagine and plan their behavior in emotional and nonemotional situations while their regional cerebral blood flow was measured with positron emission tomography. The dorsolateral prefrontal and posterior temporal cortex were more activated during the nonemotional situation whereas the medial prefrontal cortex and anterior temporal cortex were more activated during the emotional situation. These results demonstrate that distinctive regions of the prefrontal and temporal cortex used to imagine and plan behavior are activated during the expression of emotional and non-emotional plans.

Adult

Functional magnetic resonance imaging of the brain.

This conference reviewed the potential scope of application of recently developed techniques for functional magnetic resonance imaging (fMRI) of the brain. The most successful technique is based on the sensitivity of magnetic resonance imaging (MRI) to magnetic effects caused by the modulation of the oxygenation state of hemoglobin, which is induced by local variations in blood flow during task activation. Typically, the MRI signal increases by a few percentage points during brain activation because blood flow and oxygen supply sharply increase. Brain activation images with excellent combined spatial and temporal resolution have been obtained noninvasively using visual, sensorimotor, or auditory stimuli, or during higher-order cognitive processes such as language or mental imagery. Although sensitive to misregistration artifacts and macroscopic vessels, MRI permits both the direct correlation of function with underlying anatomy and repeated studies on the same person. It may become the method of choice for studies of mental and cognitive processes, presurgical mapping, monitoring recovery from stroke or head injuries, exploration of seizure disorders, or monitoring the effects of neuropharmaceuticals.

Animals

Regional cerebral blood flow changes in motor cortical areas after transient anesthesia of the forearm.

To study the effect of deafferentation on cortical areas activated by movement of the proximal muscles, we measured regional cerebral blood flow with positron emission tomography and 15O-labeled water. Flexion-extension movements of the right elbow before deafferentation were associated with an increase of regional cerebral blood flow in the primary sensorimotor area bilaterally, posterior supplementary motor area bilaterally, ipsilateral cerebellum, contralateral putamen, premotor area, anterior cingulate area, and posterior parietal region. Transient anesthesia of the right forearm induced by ischemic block caused an increase of regional cerebral blood flow in the primary sensorimotor area bilaterally at rest, but there was no change of regional cerebral blood flow with movement, indicating that the movement-related change in cerebral blood flow was reduced. These findings are consistent with increased excitability of neurons as a result of deafferentation. In the supplementary motor area, anesthesia did not induce any change in regional cerebral blood flow at rest, but there was a decline with movement, again indicating a reduction of the change in cerebral blood flow related to movement. This might be due to a reduction in sensory feedback because of the anesthesia.

Adult

The role of reading activity on the modulation of motor cortical outputs to the reading hand in Braille readers.

We studied the cortical motor output maps of the first dorsal interosseous (FDI) of both hands and the abductor digiti minimi of the reading hand in 6 blind proficient Braille readers. The maps were generated using transcranial magnetic stimulation. We compared the maps obtained on a day in which they worked as Braille proofreaders (reading Braille for approximately 6 hours) with the maps obtained on a day they took off from work. On the work day, the maps for the FDI of the reading hand were significantly larger after the working shift than in the morning after having been off work for 2 days. These changes were not seen for the same muscle on the day off work or on any of the 2 days in the other two muscles studied. These results illustrate the rapid modulation in motor cortical outputs in relation to preceding activity and emphasize the importance of precise timing in studies of the neurophysiological correlates of skill acquisition.

Adult

Changes in cerebral blood flow induced by balloon test occlusion of the internal carotid artery under hypotension.

Balloon test occlusion (BTO) of the internal carotid artery (ICA) combined with cerebral blood flow (CBF) study has proved to be a sensitive test for prediction of the outcome of permanent vessel occlusion. In this study, we evaluated the acute changes in regional CBF during BTO under hypotension in order to examine the possible risk of cerebral ischaemia after surgical treatment. Eleven patients in whom surgical carotid sacrifice was planned underwent BTO combined with CBF studies using technetium-99m hexamethyl-propylene amine oxime single-photon emission tomography under hypotension by decreasing the systemic blood pressure by about 50 mm Hg using a ganglion blocking agent. All patients showed a mild to severe decrease in CBF in the ipsilateral ICA territory relative to the contralateral side. A decrease in CBF of greater than 20% was observed in nine patients (82%), and two of them showed a decrease exceeding 40%. However, no ischaemic symptoms were demonstrated during scanning with hypotensive BTO. Our results suggest that in many patients with negative normotensive BTO, a considerable reduction in CBF would occur during hypotension. This procedure may predict a possible risk of hypotensive accident during and/or after surgery.

Adult

Clinical application of 62Zn/62Cu positron generator: perfusion and plasma pool images in normal subjects.

We have developed a new 62Zn/62Cu positron generator, and applied it for PET imaging of perfusion and plasma volume in 5 normal subjects. The generator makes it possible by a simple procedure to obtain 62Cu eluate and labeling compounds sufficiently every 40-60 minutes. 62Cu labeled pyruvaldehyde bis(N4-methylthiosemicarbazone) copper II (62Cu-PTSM) was employed for cerebral and myocardial perfusion imaging and 62Cu labeled human serum albumin-dithiosemicarbazone (62Cu-HSA-DTS) was used for plasma pool imaging. The images of cerebral blood flow, cerebral plasma volume and myocardial perfusion were excellent. In addition, the analysis of tissue activity and blood activity demonstrated the microspheric character of 62Cu-PTSM. Correction of arterial activity with the standard disappearance curve of 62Cu-PTSM suggested the possibility of quantifying blood flow. The results of this study indicate the capability of the 62Zn/62Cu generator for wide clinical use without an in-house cyclotron.

Adult

Effects of stimulus rate on regional cerebral blood flow after median nerve stimulation.

The primary motor cortex and supplementary motor area (SMA) are purportedly involved in the generation of the P22 and N30 components of somatosensory evoked potentials (SEPs) evoked by electrical stimulation of the median nerve at the wrist. We used regional cerebral blood flow (rCBF) measurements and PET in 10 normal subjects to study the cerebral areas activated by median nerve electrical stimulation. PET scans were performed with the subjects at rest and during stimulation of the right median nerve at frequencies of up to 20 Hz. Stimulation evoked a single focus of activation in the primary somatosensory area (SI). An increase of rCBF in this area was linearly correlated with stimulus frequencies of up to 4 Hz and then reached a plateau. The SMA was not significantly activated by stimulation at any of the frequencies tested. In contrast to the SI, the SMA showed no trend toward a correlation between the rCBF changes and the stimulus repetition rate. In order to achieve maximal resolution in the sensorimotor cortex, regions of interest were placed in individual co-registered MRI-PET images on both sides of the central sulcus. There was no significant increase of rCBF in the crown of the precentral gyrus. These results suggest that a contribution of the primary motor cortex and the SMA to the generation of the P22 and N30 components of SEPs is unlikely. Consequently, functional clinical interpretations derived from P22 or N30 abnormalities must be reconsidered.

Adult

Delayed data acquisition for optimal PET activation studies with oxygen-15-water in cerebral arteriovenous malformation.

UNLABELLED: In the clinical application of activation PET studies with 15O-water, optimal PET images are required when the high activity of a nearby lesion might affect the activated area. METHODS: To determine the optimal time for data acquisition of PET images, we performed serial dynamic PET measurements in five patients with cerebral arteriovenous malformation (AVM). All AVMs were closest to the motor cortices, and the activation task was opponent finger movement contralateral to the AVM. Activation PET and MR images were coregisterated for localization of activated foci. RESULTS: Time-activity curves of the nidus and normal cortex from the dynamic PET data demonstrated a discrepancy in peak time and significant radioactivity increase in the nidus during the early phase. Elimination of the initial PET data provided better contrast in activated foci without affecting the calculated cerebral blood flow of other areas. CONCLUSION: Delayed data acquisition can avoid interference of the AVM nidus with the activated area.

Adult

Spinal epidural abscess with gadolinium-enhanced MRI: serial follow-up studies and clinical correlations.

We reviewed serial MRI with and without gadolinium-DTPA in eight patients with spinal epidural abscess and correlated the findings and the clinical manifestations. In four patients, diffuse abscesses spanned four vertebral bodies or more; the others had focal abscesses associated with osteomyelitis and/or diskitis. In three of the four patients with diffuse abscesses, MRI (NCMRI) showed diffuse encasement of the subarachnoid space. Contrast-enhanced MRI (CEMRI) demonstrated linear enhancement surrounding unenhanced pus. In the four patients with focal abscesses, CEMR delineated the inflammatory process more clearly than NCMR. On follow-up studies, decrease in abscess size and better visualization of the subarachnoid space correlated with clinical improvement in both diffuse and focal abscesses. Despite clinical improvement, contrast enhancement persisted in the disk or epidural space of three patients, and was thought to represent chronic granulomatous change or postsurgical scar. CEMR is very valuable for the initial diagnosis of an epidural abscess, particularly if it involves lengthy segments. During follow-up, CEMR can document responses to therapy, and provide information for determining appropriate treatment.

Abscess