Biomedical subjects

Koji Inui

Publications and source records attributed to Koji Inui.

At least 37 records · Page 2Linked to original sources

PubMed2005

Mismatch responses related to temporal discrimination of somatosensory stimulation.

OBJECTIVE: To determine the existence of a pre-attentively evoked somatosensory mismatch negativity component and to investigate the use of that component in objective clinical diagnostics. METHODS: First we determined the temporal discrimination threshold (DT) of paired stimuli in each subject, and applied two sequential electrical stimuli to the hand with paired stimulus times of (1) DT-10 ms, (2) DT-30 ms and (3) DT+50 ms. Then, we recorded ERPs using an oddball paradigm, frequent (standard) and rare (deviant). We used two stimuli, DT-30 ms and DT-10 ms, in the first experiment, and DT-30 ms and DT+50 ms, in the second experiment. RESULTS: In each experiment, two specific components, a negative component peaking at approximately 60ms (N60) and a large positive component peaking around 100-200 ms (P150), were identified, mainly following the deviant stimulus, which were considered somatosensory mismatch components. N60 was more remarkably identified in the second experiment and P150 in the first. CONCLUSIONS: N60 might be generated during tasks which subjects can clearly discriminate, but P150, which seems to correspond to auditory mismatch negativity, might be generated in tasks which require fine discrimination. SIGNIFICANCE: We confirmed that our new method could be used for the objective examination of temporal discrimination.

Adult↗

PubMed2005

Functional relationship between human rolandic oscillations and motor cortical excitability: an MEG study.

Synchronization and desynchronization of the neural rhythm in the brain play an important role in the orchestration of perception, motor action and conscious experience. Based on the results of electrocorticographic and magnetoencephalographic (MEG) recordings, it has been considered that human rolandic oscillations originate in the anterior bank of the central sulcus (20-Hz rhythm) and the postcentral cortex (10-Hz rhythm): the 20-Hz oscillation is closely related to motor function, while the 10-Hz rhythm is attributed mainly to sensory function. To test whether the rolandic oscillations are functionally relevant to the motor cortical excitability, we examined effects of 1-Hz repetitive transcranial magnetic stimulation (rTMS) of the left primary motor cortex (M1) on movement-related changes of the rolandic oscillations in 12 normal subjects. MEG data recorded during brisk extension of the right index finger in two different sessions (with and without rTMS conditioning) were compared. Motor-evoked potential (MEP) of the right hand muscle was also measured before and after rTMS to assess the motor cortical excitability. We found that 1-Hz rTMS over M1 significantly reduced the movement-related rebound of the 20-Hz oscillation in association with decreased motor cortical excitability. In particular, movement-related rebound of the 20-Hz rhythm was closely tied with motor cortical excitability. These findings further strengthen the notion of functional relevance of 20-Hz cortical oscillation to motor cortical excitability. In the framework of previous studies, the decrease in movement-related rebound may be regarded as a compensatory reaction to the inhibited cortical activity.

Adult↗

PubMed2005

Differential modulation in human primary and secondary somatosensory cortices during the preparatory period of self-initiated finger movement.

To elucidate the mechanisms underlying sensorimotor integration, we investigated modulation in the primary (SI) and secondary (SII) somatosensory cortices during the preparatory period of a self-initiated finger extension. Electrical stimulation of the right median nerve was applied continuously, while the subjects performed a self-initiated finger extension and were instructed not to pay attention to the stimulation. The preparatory period was divided into five sub-periods from the onset of the electromyogram to 3000 ms before movement and the magnetoencephalogram signals following stimulation in each sub-period were averaged. Multiple source analysis indicated that the equivalent current dipoles (ECDs) were located in SI and bilateral SII. Although the ECD moment for N 20 m (the upward deflection peaking at around 20 ms) was not significantly changed, that for P 30 m (the downward deflection peaking at around 30 m) was significantly smaller in the 0- to -500-ms sub-period than the -2000- to -3000-ms sub-period. As for SII, the ECD moment for the SII ipsilateral to movement showed no significant change, while that for the contralateral SII was significantly larger in the 0- to -500-ms sub-period than the -1500- to -2000-ms or -2000- to -3000-ms sub-period. The opposite effects of movement on SI and SII cortices indicated that these cortical areas play a different role in the function of the sensorimotor integration and are affected differently by the centrifugal process.

Adult↗

PubMed2005

Somato-motor inhibitory processing in humans: a study with MEG and ERP.

The go/nogo task is a useful paradigm for recording event-related potentials (ERPs) to investigate the neural mechanisms of response inhibition. In nogo trials, a negative deflection at around 140-300 ms (N2), which has been called the 'nogo potential', is elicited at the frontocentral electrodes, compared with ERPs recorded in go trials. In the present study, we investigated the generators of nogo potentials by recording ERPs and by using magnetoencephalography (MEG) simultaneously during somatosensory go/nogo tasks to elucidate the regions involved in generating nogo potentials. ERP data revealed that the amplitude of the nogo-N140 component, which peaked at about 155 ms from frontocentral electrodes, was significantly more negative than that of go-N140. MEG data revealed that a long-latency response peaking at approximately 160 ms, termed nogo-M140 and corresponding to nogo-N140, was recorded in only nogo trials. The equivalent current dipole of nogo-M140 was estimated to lie around the posterior part of the inferior frontal sulci in the prefrontal cortex. These results revealed that both nogo-N140 and nogo-M140 evoked by somatosensory go/nogo tasks were related to the neural activity generated from the prefrontal cortex. Our findings combining MEG and ERPs clarified the spatial and temporal processing related to somato-motor inhibition caused in the posterior part of the inferior frontal sulci in the prefrontal cortex in humans.

Adult↗

PubMed2004

Effects of ISI and stimulus probability on event-related go/nogo potentials after somatosensory stimulation.

The present study investigated the characteristics of the middle-latency negative potential of event-related potentials (ERPs) using somatosensory go/nogo tasks. We manipulated interstimulus interval (ISI) in Experiment 1 and stimulus probability in Experiment 2 and analyzed the subtracted difference waveform resulting from subtraction of the ERP evoked by the go stimulation from that evoked by the nogo stimulation. In Experiment 1, the peak latency of negativity became significantly longer as the ISI increased, but the peak amplitude was unchanged. The reaction time (RT) was longer with increasing ISI. In Experiment 2, manipulation of the stimulus probability yielded an increase in peak amplitude with decreasing probability of the nogo stimulus, but did not affect the latency. The RT increased as the probability of a nogo stimulus rose. Because manipulation of the ISI and stimulus probability elicited different brain activities, we hypothesized that manipulation of the ISI elicited a delay of the stimulus evaluation process including response inhibition, and that stimulus probability significantly affected the strength of the response inhibition process.

Adult↗

PubMed2004

In vivo studies of phenylalanine hydroxylase by phenylalanine breath test: diagnosis of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency.

Tetrahydrobiopterin (BH4)-responsive phenylalanine hydroxylase (PAH) deficiency is characterized by reduction of blood phenylalanine level after a BH4-loading test. Most cases of BH4-responsive PAH deficiency include mild phenylketonuria (PKU) or mild hyperphenylalaninemia (HPA), but not all patients with mild PKU respond to BH4. We performed the phenylalanine breath test as reliable method to determine the BH4 responsiveness. Phenylalanine breath test quantitatively measures the conversion of L-[1-13C] phenylalanine to 13CO2 and is a noninvasive and rapid test. Twenty Japanese patients with HPA were examined with a dose of 10 mg/kg of 13C-phenylalanine with or without a dose of 10 mg . kg(-1) . d(-1) of BH4 for 3 d. The phenylalanine breath test [cumulative recovery rate (CRR)] could distinguish control subjects (15.4 +/- 1.5%); heterozygotes (10.3 +/- 1.0%); and mild HPA (2.74%), mild PKU (1.13 +/- 0.14%), and classical PKU patients (0.29 +/- 0.14%). The genotypes in mild PKU cases were compound heterozygotes with mild (L52S, R241C, R408Q) and severe mutations, whereas a mild HPA case was homozygote of R241C. CRR correlated inversely with pretreatment phenylalanine levels, indicating the gene dosage effects on PKU. BH4 loading increased CRR from 1.13 +/- 0.14 to 2.95 +/- 1.14% (2.6-fold) in mild PKU and from 2.74 to 7.22% (2.6-fold) in mild HPA. A CRR of 5 to 6% reflected maintenance of appropriate serum phenylalanine level. The phenylalanine breath test is useful for the diagnosis of BH4-responsive PAH deficiency and determination of the optimal dosage of BH4 without increasing blood phenylalanine level.

Adolescent↗

PubMed2004

Effects of citrin deficiency in the perinatal period: feasibility of newborn mass screening for citrin deficiency.

Deficiency of citrin due to mutations of the SLC25A13 gene causes adult-onset type II citrullinemia (CTLN2) and one type of neonatal intrahepatic cholestasis (NICCD). About half of the NICCD patients are detected based on high galactose, phenylalanine, and/or methionine concentrations on newborn mass screening (NMS). To clarify the perinatal and neonatal effects and the inconsistent results on NMS, we examined aminograms, the levels of bile acids and galactose in dried blood spots for NMS from 20 patients with NICCD. Birth weight was low for gestational age (-1.4 +/- 0.7 SD). Affected fetuses may have suffered intrauterine citrin deficiency. The first abnormality detected after birth was citrullinemia, and 19 of 20 patients had citrulline levels higher than +2 SD of controls. Tyrosine, phenylalanine, methionine, galactose, and bile acids were less affected than citrulline on d 5 after birth. Galactose and bile acids levels were increased at 1 mo in comparison with d 5 after birth due to impairment of the cytosolic NADH reducing-equivalent supply into mitochondria of hepatocytes. Patients with negative findings on NMS had low levels of total 20 amino acids. Citrulline/serine, citrulline /leucine plus isoleucine, and citrulline/total amino acids ratios, controlled for the confounding effect of low amount of total amino acids, were higher in all patients than +2 SD, +2 SD, and +3 SD of controls, respectively. NMS for citrin deficiency (frequency of homozygote with SLC25A13 mutation: 1/10,000-1/38,000 in East Asia) will be useful for clarification of the clinical course, treatment, and prevention of this disease.

Amino Acids↗

PubMed2004

Temporal dynamics of neural adaptation effect in the human visual ventral stream.

When the same visual stimulus is repeatedly presented with a brief interval, the brain responses to that stimulus are attenuated relative to those at first presentation [neural adaptation (NA)]. Although this effect has been widely observed in various regions of human brain, its temporal dynamics as a neuronal population has been mostly unclear. In the present study, we used a magnetoencephalography (MEG) and conducted a macrolevel investigation of the temporal profiles of the NA occurring in the human visual ventral stream. The combination of MEG with our previous random dot blinking method isolated the neural responses in the higher visual cortex relating to shape perception. We dissociated three dimensions of the NA: activation strength, peak latency, and temporal duration of neural response. The results revealed that visual responses to the repeated compared with novel stimulus showed a significant reduction in both activation strength and peak latency but not in the duration of neural processing. Furthermore, this acceleration of peak latency showed a significant correlation with reaction time of the subjects, whereas no correlation was found between the reaction time and the temporal duration of neural responses. These results indicate that (1) the NA involves the brain response changes in the temporal domain as well as the response attenuation reported previously, and (2) this temporal change is primarily observed as a rapid rising of "what" responses, rather than a temporal shortening of neural response curves within the visual ventral stream as considered previously.

Adult↗

PubMed2004

Analysis of recombinant human saposin A expressed by Pichia pastoris.

Saposins (SAPs) are small glycoproteins required for activation of sphingolipid hydrolysis by lysosomal enzymes. Four SAPs, SAP-A, -B, -C, and -D, are proteolytically cleaved from a single gene product termed prosaposin. The mature coding sequence of human SAP-A tagged with 6-histidine was expressed in Pichia pastoris and the recombinant protein was purified from the culture supernatant by simple purification steps with an immobilized metal ion affinity column, a Concanavalin A column, and reversed-phase HPLC. Secreted SAP-A contained both glycosylated and nonglycosylated forms. Both forms of SAP-A activated galactocerebroside and 4-methylumbelliferyl beta-d-glucoside hydrolysis by galactocerebrosidase and glucocerebrosidase. SAP-A expressed in P. pastoris should be useful for further structural and functional analysis of this protein.

Amino Acid Sequence↗

PubMed2004

Serial processing in the human somatosensory system.

Although numerous anatomical and electrophysiological findings in animal studies have supported a hierarchical scheme of somatosensory processing, precise activation timings of each cortical area are not known. Therefore we examined the temporal relationship of activities among multiple cortical areas using magnetoencephalography in humans. We found activations in Brodmann's areas 3b, 4, 1, 5 and the secondary somatosensory cortex region in the right hemisphere following transcutaneous electrical stimulation of the dorsum of the left hand. The mean onset latencies of each cortical activity were 14.4, 14.5, 18.0, 22.4 and 21.7 ms, respectively. The differences of onset latencies among these activations indicated the serial mode of processing both through the postcentral gyrus and through the primary and secondary somatosensory cortices.

Adult↗

PubMed2004

Effects of a go/nogo task on event-related potentials following somatosensory stimulation.

OBJECTIVE: We investigated the effects of a go/nogo task on event-related potentials (ERPs) evoked by somatosensory stimuli. METHODS: ERPs following electrical stimulation of the second (go stimulus) or fifth (nogo stimulus) left-handed digit were recorded from 9 subjects. The recordings were conducted in 3 conditions: Control, Count and Movement. The subjects were instructed to count the go stimuli silently in Count, and respond to the go stimuli by grasping right hands in Movement. Go and nogo stimuli were presented at an even probability. RESULTS: N140 was recorded in all conditions and P300 in Count and Movement. The mean amplitudes of the nogo stimuli in the interval 140-200 msec and nogo-N140 amplitude were significantly more negative than those of the go stimuli in Count or Movement. Nogo-P300 was larger in amplitude than go-P300 in Movement but not Count. The effect of P300 was applied to Fz and Cz, but not at Pz. CONCLUSIONS: In the present study, effects of a somatosensory go/nogo task on ERPs were investigated, and our findings were very similar to those of previous studies using visual and auditory go/nogo tasks. Therefore, we suggest that cortical activities relating to go/nogo tasks are not dependent on sensory modalities. SIGNIFICANCE: The present study showed for the first time the go/nogo effects on somatosensory-evoked ERPs. These effects were similar to those in visual and auditory ERP studies.

Acoustic Stimulation↗

PubMed2004

Effects of distraction on magnetoencephalographic responses ascending through C-fibers in humans.

OBJECTIVE: Using magnetoencephalography (MEG), we evaluated the cerebral regions relating to second pain perception ascending through C-fibers and investigated the effect of distraction on each region. METHODS: Thirteen normal subjects participated in this study. CO2 laser pulses were delivered to the dorsum of the left hand to selectively activate C-fibers. The MEG responses were analyzed using a multi-dipole model. RESULTS: (1) primary somatosensory cortex (SI), and (2) secondary somatosensory cortex (SII)--insula were the main generators for the primary component, 1M, whose mean peak latency was 744 ms. In addition to (1) and (2), (3) cingulate cortex and (4) medial temporal area (MT) were also activated for the subsequent component, 2M, whose mean peak latency was 947 ms. During a mental calculation task (Distraction), all 6 sources were significantly reduced in amplitude, but the SII-insula (P < 0.01) and cingulate cortex (P < 0.001) were more sensitive than the SI (P < 0.05) and MT (P < 0.05). CONCLUSIONS: We confirmed that SI in the contralateral hemisphere and SII-insula, cingulate cortex and MT in bilateral hemispheres play a major role in second pain perception, and all sites were much affected by a change of attention, indicating that these regions are related to the cognitive aspect of second pain perception. SIGNIFICANCE: The SI, SII, cingulate and MT were activated during the C-fiber-related MEG response, and responses in these regions were significantly diminished during mental distraction.

Adult↗

PubMed2004

Cognitive processes in two-point discrimination: an ERP study.

OBJECTIVE: To elucidate the temporal features of the cognitive process in two-point discrimination (TPD). METHODS: We measured somatosensory event-related potentials (ERPs) in 9 subjects during the TPD task, in which we provided a pair of electrical pulses simultaneously, altering the distance between the electrodes. We analyzed the TPD-related ERPs and investigated the relationship between the potentials and the subjects' judgments. RESULTS: During the TPD task, a negative potential approximately 140 ms after the stimulation (N140) was enhanced as compared to a stimulus counting task. Two late positive components, LPC-1 and LPC-2, whose peak latencies were 300 and 500 ms, respectively, were identified only in the TPD task. The LPC-1 was recorded dominantly in the fronto-central area, while the LPC-2 was detected dominantly in the centro-parietal area. The amplitude of the LPC-2 was significantly modulated by the degree of consistency in the subjects' judgment. On the other hand, these ERP components did not show significant difference between the alternate judgments, i.e. 'one-point' or 'two-point' judgment. CONCLUSIONS: Our results suggest that the N140 is related to the attention toward the stimulation. The LPC-1 and LPC-2 are likely to correspond to the processes represented by P3a and P3b, based on their temporal and spatial behavior.

Adult↗

PubMed2004

Face representation in the human primary somatosensory cortex.

To investigate the representation of facial skin areas in the primary somatosensory cortex (SI), we recorded magnetic fields evoked by air pressure-induced tactile stimulation applied to six points on the face, lower lip and thumb. The thumb area in the SI was located more medial and superior to the lip area, which was consistent with Penfield's homunculus. However, the representations of all skin-covered areas including forehead, cheek, nose and chin in the SI were located between the thumb and lower lip area. There was no significant difference in location among the six facial points. Our results imply that lips occupy a large area of the face representation in the SI, whereas only a small area located between the thumb and lip areas is devoted to skin-covered surfaces. This is the first study showing that the facial skin areas in the human SI are located between the thumb and lower lip areas and close together.

Adult↗

PubMed2004

Movements modulate cortical activities evoked by noxious stimulation.

To evaluate the effects of movement on cortical activities evoked by noxious stimulation, we recorded magnetoencephalography following noxious YAG laser stimulation applied to the dorsum of the left hand in normal volunteers. Results of the present study can be summarized as follows: (1) active movement of the hand ipsilateral to the side of noxious stimulation resulted in significant attenuation of both primary and secondary somatosensory cortices (SI and SII) in the hemisphere contralateral to the stimulated hand (cSI and cSII). Activity in the hemisphere ipsilateral to the side of stimulation (iSII) was not affected. (2) Active movement of the hand contralateral to the side of noxious stimulation resulted in significant attenuation of cSII. Activity in cSI and iSII was not affected. (3) Passive movement of the hand ipsilateral to the side of noxious stimulation resulted in significant attenuation of cSI. Activity in cSII and iSII was not affected. (4) Visual analogue scale (VAS) changes showed a similar pattern to the amplitude changes of cSII. These results suggest that activities in three regions are modulated by movements differently. Inhibition in cSI was considered to be mainly due to an interaction in SI by the signals ascending from the stimulated and movement hand. Inhibition in cSII was considered to be mainly due to particular brain activities relating to motor execution and/or movement execution associated with a specific attention effect. In addition, since VAS changes showed a similar relationship with the amplitude changes of cSII, cSII may play a role in pain perception.

Adult↗

PubMed2004

Human brain processing and central mechanisms of pain as observed by electro- and magneto-encephalography.

We review the recent progress of electroencephalography (EEG) and magnetoencephalography (MEG) to elucidate pain perception mechanisms in humans, since EEG and MEG have an excellent temporal resolution in order of msec. MEG is more useful to detect activated areas following painful stimulation, because the spatial resolution of EEG is not very high. For recording activities following Adelta fiber stimulation relating to the first pain, painful CO2 laser stimulation is now widely used, but our new method, epidermal stimulation (ES), is also very useful. The primary small activity was recorded from the primary somatosensory cortex (SI), probably in area 1, in the hemisphere contralateral to the stimulation. Then, secondary somatosensory cortex (SII) and insula were activated with the second activity in SI. These 3 regions were activated in parallel with almost the same time period. This is a very characteristic finding in pain perception. Then, the cingulate cortex and medial temporal area (MT) around the amygdala and hippocampus were activated. In the hemisphere ipsilateral to the stimulation as well, the above regions were activated, except for SI. Therefore, we speculated that SI plays a main role in localization of the stimulus point, the SII and insula are important sites for pain perception, and the cingulate and MT are mainly responsible for cognitive or emotional aspects of pain perception. For recording activities following C fiber stimulation relating to the second pain, we recently developed a new method, that is, applying weaker CO2 laser stimuli to tiny areas of the skin. MEG findings following C fiber stimulation were also similar to those following Adelta fiber stimulation. However, the effects of sleep and attention on MEG following C fiber stimulation was much larger than that following Adelta fiber stimulation. This finding may suggest greater effects of cognitive or emotional functions on second pain than the first pain.

Brain↗

PubMed2003

Microneurographic study of C fiber discharges induced by CO2 laser stimulation in humans.

We investigated C-fiber discharges and cerebral potentials evoked by weak CO(2) laser beams applied to a tiny skin area in five healthy subjects. Microneurography was performed from the peroneal nerve in the right popliteal area. Cerebral potentials were recorded from the Cz electrode referred to linked earlobes. The mean conduction velocity of five stable single units was 1.1+/-0.3 m/s. The mean latency of the positive peak of cerebral potentials was 1327.4+/-46.2 ms. These findings indicated that this new stimulation method selectively activated C-fiber nociceptors of the skin.

Adult↗

PubMed2003

Central mechanisms for two-point discrimination in humans.

We studied the cognitive mechanisms for two-point discrimination (TPD) in 11 normal subjects, using electrical pulses. We used six ball-shaped electrodes placed in line on the dorsal surface of the left hand, and two-point was stimulated by two electrodes randomly selected. We measured the reaction time for TPD and calculated the percentage of correct responses for each two-point stimulation. The subjects' response was significantly affected by the preceding stimuli as well as the distance of the stimuli: for a two-point stimulus condition, subjects tended to feel the stimuli as two-point when the distance between the stimuli was longer than that of preceding stimuli, whereas they felt the stimuli as one-point when the distance was shorter than that of the preceding stimuli. The present results indicate that the TPD process involved evaluation of the distance between the stimuli relatively to that of the preceding stimuli, as well as evaluation of absolute distance between the stimuli.

Adult↗