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PubMed2000

Functional coupling of human right and left cortical motor areas demonstrated with partial coherence analysis.

Although a linear correlation between oscillatory activities in the right and left motor cortices during movements has been shown in monkeys, there has been a debate whether scalp-recorded EEG coherence in human reflects a similar association. By applying partial coherence analysis, we demonstrated that interhemispheric coherence during movements cannot be explained by contamination from the occipital alpha rhythm or common reference signal. A significant increase of net interhemispheric communication in the beta1 band was shown during movements. We propose that the partial coherence method can be a useful tool to measure cortico-cortical functional coupling reliably.

Adult↗
PubMed2001

Characterization of 5' flanking region of alpha isoform of rat Ca2+/calmodulin-dependent protein kinase II gene and neuronal cell type specific promoter activity.

The 5' flanking region of the alpha isoform of the rat Ca2+/calmodulin-dependent protein kinase II (alpha CaM kinase II) gene was isolated in 2.3 kbp of genomic sequence. Functional analysis of alpha CaM kinase II promoter deletion mutants fused to a reporter gene in neuroblastoma, including N18TG2, NG108-15, and CAD cells revealed strong transcriptional activity localized 100-145 bp, and a potent silencer 199-275 bp upstream of the transcription start site. The promoter is inactive in non-neuronal cells including BALB/c 3T3, Chinese hamster ovary, HT1080, and C6 glioma cells. These results indicated that the alpha CaM kinase II gene is transcribed from a tissue-specific promoter which is under intense negative control.

Animals↗
PubMed1998

Human supplementary motor area is active in preparation for both voluntary muscle relaxation and contraction: subdural recording of Bereitschaftspotential.

Bereitschaftspotentials (BPs) preceding muscle relaxation and contraction were compared by using subdural electrodes which were implanted onto the right medial frontal surface in two patients with supplementary motor area (SMA) seizure. The applied movement paradigm (muscle relaxation and contraction tasks) was completely the same as employed in our previous study [Terada, K., Ikeda, A., Nagamine, T. and Shibasaki, H., Electroenceph. clin. Neurophysiol., 95 (1995) 335-345]. In both patients, either negative or positive BPs were observed in the SMA-proper and supplementary negative motor area (SNMA) starting at 1.2-1.8 prior to both movements. In one patient, BP was more widespread in the relaxation task whereas more restricted to the hand area in the contraction task. In the other patient, the BPs were observed in the cortical area rostral to SNMA (pre-SMA), in addition to the SMA-proper, in both tasks. It is concluded that SMA-proper and SNMA, and probably pre-SMA as well, in humans are similarly active in preparation for both voluntary muscle contraction and relaxation.

Adult↗
PubMed1999

Force level modulates human cortical oscillatory activities.

We studied the relationship between cortical and muscular oscillatory activities and muscular force level during a tonic contraction task using electroencephalography (EEG). Within the weak to moderate force level, the normalized power in the alpha band in the contralateral sensorimotor areas was inversely linearly correlated with the force. Cortical-muscular coherence was observed in the beta band and its magnitude was not affected by the force. In contrast, during strong contractions, EEG power in the gamma band increased and was partly correlated with the Piper rhythm in the electromyogram. Our results show that the multiple oscillatory activities in the cortex are correlated with the force level in different ways. Cortical gamma band oscillation may reflect both focused attention and the efferent drive to the muscle during very strong tonic contraction.

Adult↗
PubMed2000

Argatroban, a thrombin inhibitor, decreased mortality after 10 min of forebrain ischemia in the gerbil.

We investigated whether anticoagulant therapy with heparin or a selective thrombin inhibitor, argatroban, may ameliorate the postischemic cerebral circulation and attenuate mortality after 10 min of forebrain ischemia. Postischemic subcutaneous injection of argatroban (5 mg/kg) significantly attenuated mortality (9.1%) compared with non-treatment (45.5%) during 14 days' observation period. This effect coincided with: (1) increased cortical CBF after reperfusion; (2) attenuation of brain edema; and (3) less severe cell damages in the cerebral cortex. In contrast, nine of the 22 gerbils treated with heparin (830 IU/kg) were found dead on the next day due to massive bleeding in the surgical wound and 13 bleeding-avoided gerbils did not show significant amelioration in mortality (30.8%). These findings suggest that argatroban is an effective anticoagulant for prevention of cell damage after a relatively long forebrain ischemia.

Animals↗
PubMed1998

Simultaneous expression of brain-derived neurotrophic factor and neurotrophin-3 in Cajal-Retzius, subplate and ventricular progenitor cells during early development stages of the rat cerebral cortex.

To identify production sites and action targets of neurotrophins during neurogenesis, we investigated immunoreactivities of neurotrophins and their tyrosine kinase receptors in the cerebral cortex of rat embryos. Two sets of ligand-receptor systems, brain-derived neurotrophic factor/TrkB and neurotrophin-3/TrkC, were expressed simultaneously in Cajal-Retzius, subplate neurons and ventricular multipotent stem cells at embryonic days 13 and 15. Intraventricular administration of brain-derived neurotrophic factor or neurotrophin-3 at embryonic day 16 markedly modulated microtubule-associated protein II and/or Hu protein expression in different ways in the cortical plate cells by embryonic day 20. These observations indicate the involvement of autocrine and/or local paracrine action of brain-derived neurotrophic factor and/or neurotrophin-3 during formation of the cerebral cortex.

Aging↗
PubMed1998

The ultrastructural characteristics of eccrine sweat glands in a Fabry disease patient with hypohidrosis.

As an investigation of the pathogenetic mechanism of diminished sweating in Fabry disease, an electron microscopy ultrastructural study was conducted on specimens of eccrine sweat glands from a typical patient with Fabry disease who had hypohidrosis, a low skin moisture content, and diminished thermoregulation ability. Numerous characteristic cytoplasmic inclusions were observed in the eccrine sweat glands, the lamellar pattern of which was considerably variable in various types of gland cells. Large vacuolar inclusions predominated in clear cells of secretory coil; lesser vacuoles were also seen in the coiled duct, and the basal cells of the straight duct toward the coiled duct displayed mulberry-like figures. There were some clear cells showing cell damage and necrosis in the secretory coil. Lamellated inclusions were noted in the unmyelinated axons innervating the eccrine sweat glands. The small blood vessels around the eccrine glands were narrowed by swollen endothelial cells with heavy inclusions. These intracytoplasmic deposits may be responsible for the decreased sweating ability in Fabry disease. The factors related to hypohidrosis are also discussed.

Eccrine Glands↗
PubMedDate not supplied

Structural gene products and morphogenesis of a hybrid between rubella virus and a hamster latent retrovirus.

We studied the structural gene products and morphogenesis of the hybrid between rubella virus (RV) and a latent retrovirus (R-type virus or R virus) of a baby hamster kidney cell line, BHK21/WI-2. In electron microscopic analysis, the rubella virion measures 80 nm in diameter and has a round nucleoid form with an electron-lucid centre, while R-type virus is 110 nm in diameter and has a round nucleoid with radial spokes. The type 2 hybrid (H2) virion is pleomorphic, ranging from 85 to 110 nm in diameter, and has a nucleoid structure similar to R virus, with short spokes. Indirect immunofluorescence staining of H2-infected cells with polyclonal and monoclonal antibodies (mAb) against the RV structural proteins demonstrated expression of the homologous RV gene products. SDS-PAGE of 35S-methionine-labelled proteins in RV- and H2-infected cells revealed that they both produce four major immunoprecipitable proteins, three of which (E2a, E2b and C) are products of the two genetic homologous loci (e2 and c). In nonhomologous regions, RV-infected cells exhibited E1 protein, while H2-infected cells produced the Env protein of R virus. Western immunoblotting analysis of RV and H2 viral proteins with mAb confirmed that H2 virions carry rubella viral E2 and C proteins and that E1 protein is carried by RV but not H2 virion. These results explained the absence of serological cross-neutralization of haemagglutination and plaque-forming ability of RV and H2 viruses.

Animals↗
PubMed2002

Second somatosensory area (SII) plays a significant role in selective somatosensory attention.

In order to explore human cortical areas involved in active attention toward a somatosensory modality, somatosensory evoked cortical magnetic fields were recorded in ten healthy adults with a 122-channel whole-head magnetometer while the subjects performed the selective attention task. Two kinds of stimulus modality, somatosensory and auditory, were presented independently in the same session. For the somatosensory modality, a randomized sequence of strong (P=0.45) and weak (P=0.05) electric stimuli was delivered to the right median nerve at the wrist. For the auditory modality, a randomized sequence of 900-Hz (P=0.45) and 950-Hz (P=0.05) tones was delivered to both ears. Subjects were requested to pay attention to the specified stimulus modality (either somatosensory or auditory) and to count the number of rare stimuli of the attended modality (weak stimuli in the somatosensory or 950-Hz tone in the auditory modality). A total of 12 sessions were performed for each subject, among which the order of attended modality was changed alternately and counterbalanced among subjects. In the data analysis, somatosensory evoked fields for frequent stimuli (strong electric stimuli) were compared between the two conditions; attend somatosensory condition (ATS) and attend auditory condition (non-attend somatosensory condition; NATS). In six out of the ten subjects, somatosensory evoked fields showed attention-related change. The magnitude of the estimated generator source in SII, but not in SI, significantly increased from NATS to ATS while keeping the same locations. Moreover, a simulation study using the estimated sources in SII in NATS supported the enhancement of the activity in the SII rather than participation of additional sources in the selective attention task. These results suggest that the SII plays a main role in selective somatosensory attention.

Acoustic Stimulation↗
PubMed2002

Terminology-driven literature mining and knowledge acquisition in biomedicine.

In this paper we describe Tagged Information Management System (TIMS), an integrated knowledge management system for the domain of molecular biology and biomedicine, in which terminology-driven literature mining, knowledge acquisition (KA), knowledge integration (KI), and XML-based knowledge retrieval are combined using tag information management and ontology inference. The system integrates automatic terminology acquisition, term variation management, hierarchical term clustering, tag-based information extraction (IE), and ontology-based query expansion. TIMS supports introducing and combining different types of tags (linguistic and domain-specific, manual and automatic). Tag-based interval operations and a query language are introduced in order to facilitate KA and retrieval from XML documents. Through KA examples, we illustrate the way in which literature mining techniques can be utilised for knowledge discovery from documents.

Artificial Intelligence↗
PubMed2001

Information flow from the sensorimotor cortex to muscle in humans.

OBJECTIVES: To investigate the physiologic mechanism of human electroencephalogram-electromyogram (EEG-EMG) coherence, the directed transfer function (DTF) based on a multivariate autoregressive (MVAR) model was computed. METHODS: Fifty-six channel EEG and EMG of the right abductor pollicis brevis muscle during a weak tonic contraction were recorded in 6 normal volunteers. The EEG over the left sensorimotor area and the rectified EMG were used to compute coherence and DTF. RESULTS: EEG-EMG coherence was observed at the peak frequency of 15-29 Hz (mean 18.5 Hz). The peak frequency of DTF from EEG to EMG was 12-27 Hz (mean 17.8 Hz). DTF from EEG to EMG was significantly larger than that from EMG to EEG at 19-30 and 45-50 Hz (P<0.05). CONCLUSIONS: The present findings suggest that the EEG-EMG coupling mechanism for the 19 Hz or higher frequency might differ from that for the lower frequency. Directional information flow from EEG to EMG in the former frequency range likely reflects the motor control command. The finding of the directional information flow from EEG to EMG within the gamma band indicates that 40 Hz EEG-EMG coherence is not specific to the muscle Piper rhythm which is seen only with strong contraction.

Adult↗
PubMed2002

Cortical potentials related to assessment of pain intensity with visual analogue scale (VAS).

OBJECTIVES: To elucidate brain mechanisms underlying the psychophysical processes to measure pain intensity, pain-related somatosensory evoked potentials (pain SEPs) following painful CO(2) laser stimulation were studied while employing a task to measure intensity of pain on a visual analogue scale (VAS). METHODS: In 12 healthy subjects, 3 kinds of CO(2) laser stimuli, different in intensity as determined by irradiation duration of 40, 60 and 80ms, were randomly delivered to the left hand dorsum at an irregular interval of 4-6s. The subject was requested to assess the intensity of each pain stimulus and point to the VAS scale by moving a pointer held with the right hand according to the subjective feeling of pain sensation (pain intensity assessment (PIA) condition). For the control condition, the subject moved the pointer to the midpoint of the VAS line irrespective of the pain intensity (control motor task condition). Electroencephalograms were recorded from 21 scalp electrodes, referenced to the linked earlobes, and were averaged time-locked to the stimulus onset for each stimulus duration as well as for each task condition. RESULTS: The VAS scores were 2.8+/-0.5/10 for the stimulus of 40ms duration, 4.8+/-0.8/10 for 60ms and 6.1+/-0.9/10 for 80ms, and showed a highly significant positive correlation with the stimulus duration. Following the early components of pain SEPs which were affected by stimulus duration but not modulated by task conditions, a surface-positive peak at latency of 612-642ms was identified exclusively under the PIA condition regardless of the stimulus intensity and was called 'intensity assessment-related potential (IAP)'. The IAP was maximal at the midline parietal area and symmetrically distributed over the scalp. Neither latency nor amplitude of the IAP was significantly different among the 3 different stimulus intensities. CONCLUSIONS: IAP is an event-related potential (ERP) associated with assessment of pain intensity but not influenced by pain intensity itself. From its scalp distribution, it can be assumed that the assessment of pain intensity involves multiple areas in both hemispheres.

Adult↗
PubMed2002

Nausea as a complication of low-frequency repetitive transcranial magnetic stimulation of the posterior fossa.

BACKGROUND: Transcranial magnetic stimulation (TMS) can non-invasively investigate the function of human brain. However, it can induce a focal pain at the stimulated site on the scalp or seizures when applied with high frequency (>1 Hz). Here we report an induction of nausea as a complication of low-frequency repetitive TMS (rTMS) of the cerebellum. SUBJECTS AND METHODS: Eight right-handed normal volunteers underwent low-frequency (0.9 Hz) rTMS of the right cerebellum. The stimulus intensity was set at 90% of the resting motor threshold determined by TMS to motor cortex. RESULTS: Nausea lasted as long as 10 min after the end of rTMS without apparent neurological deficit in two subjects. This symptom was replicated when the same protocol was applied on a different day in the same subjects. CONCLUSIONS: Low-frequency rTMS of cerebellum is still a safe procedure, but the experimenters should keep in mind the possibility of inducing nausea.

Adult↗
PubMed2003

Transcranial magnetic stimulation (TMS) of the sensorimotor cortex and medial frontal cortex modifies human pain perception.

OBJECTIVE: Although recent neuroimaging studies have shown that painful stimuli can produce activity in multiple cortical areas, the question remains as to the role of each area in particular aspects of human pain perception. To solve this problem we used transcranial magnetic stimulation (TMS) as an 'interference approach' tool to test the consequence on pain perception of disrupting activity in several areas of cortex known to be activated by painful input. METHODS: Weak CO(2) laser stimuli at an intensity around the threshold for pain were given to the dorsum of the left hand in 9 normal subjects. At variable delays (50, 150, 250, 350 ms) after the onset of the laser stimulus, pairs of TMS pulses (dTMS: interpulse interval of 50 ms, and stimulus intensity of 120% resting motor threshold) were applied in separate blocks of trials over either the right sensorimotor cortex (SMI), midline occipital cortex (OCC), second somatosensory cortex (SII), or medial frontal cortex (MFC). Subjects were instructed to judge whether or not the stimulus was painful and to point to the stimulated spot on a drawing of subject's hand. RESULTS: Subjects judged that the stimulus was painful on more trials than control when dTMS was delivered over SMI at 150-200 ms after the laser stimulus; the opposite occurred when dTMS was delivered over MFC at 50-100 ms. dTMS over the SII or OCC failed to alter the pain threshold. CONCLUSIONS: These results suggest that TMS to SMI can facilitate whereas stimulation over MFC suppresses central processing of pain perception. Since there was no effect of dTMS at any of the scalp sites on the localization task, the cortical locus for point localization of pain may be different from that for perception of pain intensity or may involve a more complex mechanism than the latter. SIGNIFICANCE: This is the first report that TMS of SMI facilitates while that of MFC suppresses the central processing of pain perception. This raises the possibility of using TMS as a therapeutic device to control pain.

Adult↗
PubMed2003

Low-frequency rTMS over lateral premotor cortex induces lasting changes in regional activation and functional coupling of cortical motor areas.

OBJECTIVE: To study the effect of 0.9 Hz repetitive transcranial magnetic stimulation (rTMS) of the lateral premotor cortex on neuronal activity in cortical motor areas during simple motor tasks. METHODS: In 8 subjects, electroencephalogram (EEG) and electromyogram (EMG) were simultaneously recorded during voluntary contractions of the thumb before and after a 15 min train of 0.9 Hz rTMS over the left lateral premotor cortex at stimulus intensity of 90% of active motor threshold. After-effects on cortical motor activity were assessed by measuring the task-related EEG power and inter-regional coherence changes, and the EEG-EMG coherence (EMGCoh). RESULTS: Low-frequency rTMS over the premotor cortex gave rise to (i) a reduction of the task-related power decrease in the alpha and beta bands, (ii) a selective increase in the task-related coherence change among cortical motor areas in the upper alpha band, and (iii) a decrease in the cortico-muscular coherence. These effects lasted about 15 min after the end of rTMS intervention. CONCLUSIONS: The attenuated task-related power changes and decreased EMGCoh point to a lasting suppression of voluntary activation of cortical motor areas after rTMS. The present data provide an evidence for a transient reorganization of movement-related neuronal activity in the cortical motor areas after 0.9 Hz rTMS over the premotor cortex. SIGNIFICANCE: Low-frequency rTMS changes the regional activation and functional coupling of cortical motor areas as demonstrated by EEG analysis.

Adult↗
PubMed2003

Distinct cortical areas for motor preparation and execution in human identified by Bereitschaftspotential recording and ECoG-EMG coherence analysis.

OBJECTIVE: To clarify the cortical areas involved in motor preparation and execution by investigating Bereitschaftspotentials (BPs) and electrocorticogram-electromyogram (ECoG-EMG) coherence from subdural electrodes placed around the rolandic area. METHODS: BPs and ECoG-EMG coherence were investigated for presurgical evaluation in a patient with cavernoma in the left frontal lobe. BPs were recorded in association with the tongue, right hand and right foot movements. ECoG-EMG coherence was calculated in association with weak muscle contraction of the right hand. RESULTS: Two cortical areas related to voluntary motor control were identified; one in the primary hand motor area, which generated surface-negative BPs with hand movements and showed significant coherence of ECoG with EMG of the contralateral hand muscle, and the other in the ventral rolandic area posterior to the central sulcus, which generated surface-positive BPs with voluntary movements of multiple sites (hand, tongue and foot) but did not show any ECoG-EMG coherence. CONCLUSIONS: It is postulated that the former area represents the primary motor area involved in both motor preparation and execution, and the latter area represents the non-primary motor area involved in motor preparation. SIGNIFICANCE: BP recording combined with ECoG-EMG coherence analysis could reveal the functional roles of motor cortices and the reorganization induced by structural brain lesion.

Brain Mapping↗
PubMed2000

Electroencephalographic measurement of motor cortex control of muscle activity in humans.

OBJECTIVE: To detect and measure correlation between cortical and muscle activities, coherence analysis was used. METHODS: The electroencephalogram (EEG) and electromyogram (EMG) were recorded in 9 normal volunteers during tonic contraction of upper and lower limb muscles on the right side. Coherence between EEG and EMG was computed to analyze their linear association. RESULTS: EEG over the contralateral sensorimotor area was coherent with EMG, with peak coherence at 11-36 Hz (mean, 22 Hz). For the abductor pollicis brevis (APB) muscle, peak coherence, as determined by functional brain mapping with focal transcranial magnetic stimulation (TMS), was over or slightly posterior to the hand area on the primary motor cortex determined by focal transcranial magnetic stimulation (TMS). Peak coherence over the scalp was somatotopically organized. The temporal relation between EEG and EMG was analyzed with a new model for interpreting the phase shift ('constant phase shift plus constant time lag' model). For the APB muscle, the phase relation between cortical and muscular oscillations differed in the frequency ranges of 3-13 Hz and 14-50 Hz, respectively, suggesting that different coupling mechanisms operate in different bands. Only the phase shift between cortical and motoneuronal firing at 14-50 Hz was reliably estimated by a linear model. At 14-50 Hz, motoneuronal firing was led by surface-negative cortical activity with a constant time lag that depended on the cortical-muscular distance. For the APB muscle, the time lag was slightly shorter than the cortical-muscular conduction time determined by TMS. Vibratory stimulation (100 Hz) of a muscle tendon during tonic contraction had no significant effect on cortical-muscular coherence, indicating that cortical oscillation reflected motor rather than sensory activity. CONCLUSIONS: The present findings suggest temporal coding of the oscillatory motor control system (3-13 Hz vs. 14-50 Hz), and confirm the functional importance of cortical beta and gamma rhythms in the motor efferent command. Cortical-muscular synchronization is most likely mediated by the direct corticospinal pathway within the frequency range of 14-50 Hz.

Adult↗