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PubMed2002

Frequency-dependent spatial distribution of human somatosensory evoked neuromagnetic fields.

Using synthetic aperture magnetometry (SAM), we examined the spatial distribution of frequency changes in magnetoencephalography signal rhythms on individual magnetic resonance images following somatosensory stimulation. SAM is a novel statistical spatial filtering method that uses an adaptive beamformer. Electrical stimulation of the right median nerve demonstrated high-frequency event-related synchronization (ERS) in the 50-200-Hz range, consistently localized in the contralateral primary sensorimotor area in all subjects (n=7). Event-related desynchronization (ERD) was demonstrated in the 8-13, 13-25 and 25-50-Hz ranges bilaterally in the area surrounding the central sulcus. The differences in the spatial distribution as well as the frequency bands between ERS and ERD suggest that ERS and ERD reflect the responses of different cell assemblies rather than a frequency shift of the same cell assembly.

Adult↗
PubMed2002

Absence of coherence between cervical and lumbar spinal cord dorsal surface potentials in the anaesthetized cat.

Recordings of spontaneous cord dorsum potentials (CDPs) along the longitudinal axis of the spinal cord were made. These recordings were obtained from the surface of the dorsal horn at different points along the spinal cord caudally and cranially in relation to the point giving spontaneous potentials of maximal amplitude. We found two curves (lumbar and cervical) for the longitudinal distribution of the area of the power spectra of these recordings. Each of these curves had a symmetrical decrement on both sides of the position of the point for the maximal area of power. Such points were discovered on the L5-L7 and C3-C4 spinal segments. Spectral analysis of the spontaneous CDPs simultaneously recorded in both regions indicates no evidence of coherence, thus suggesting that the spontaneous CDPs recorded in the lumbar and cervical regions of the pentobarbitone-anaesthetized cat are generated by two independent populations of neurones not functionally interconnected between them.

Action Potentials↗
PubMed2003

Inhibition of glycine response by amiloride in rat spinal neurons.

The modulatory effect of amiloride on glycine-activated current (I(Gly)) was investigated in acutely dissociated rat spinal dorsal horn neurons using the whole-cell patch clamp technique. Amiloride inhibited I(Gly) reversibly in a concentration-dependent manner. It shifted the concentration-response relationship to the right without altering the maximum response and Hill coefficient of the I(Gly). Amiloride did not change the ion selectivity of glycine receptor either. In addition, Na(+) - or Ca(2+) -free extracellular solutions and intracellular application of amiloride did not alter the amiloride inhibition of I(Gly). These results indicate that amiloride directly inhibited the glycine receptor response by decreasing the affinity of glycine to its receptor.

Amiloride↗
PubMed2001

NMDA or non-NMDA receptor antagonists attenuate increased Fos expression in spinal dorsal horn GABAergic neurons after intradermal injection of capsaicin in rats.

GABAergic neurons play an important role in the generation of primary afferent depolarization, which results in presynaptic inhibition and, if large enough, triggers dorsal root reflexes. Recent electrophysiological studies by our group have suggested that increased excitation of spinal GABAergic neurons by activation of N-methyl-D-aspartate (NMDA) and non-NMDA receptors following intradermal injection of capsaicin results in the generation of DRRs that contribute to neurogenic inflammation. The present study was to determine if changes in the expression of Fos protein occur in GABAergic neurons in the lumbosacral spinal cord following injection of capsaicin into the glabrous skin of one hind paw of anesthetized rats and if pretreatment with an NMDA receptor antagonist, D-(-)-2-amino-7-phosphonoheptanoic acid (AP7) or a non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) blocks Fos expression in these neurons. The experiments used western blots and immunofluorescence double labeling staining following capsaicin or vehicle injection. Western blots showed that Fos protein was increased on the ipsilateral side in spinal cord tissue 0.5 h after capsaicin injection. Pretreatment with AP7 or CNQX caused a decrease in capsaicin-induced Fos expression. Immunofluorescence double labeling showed that the proportion of Fos-positive GABAergic neuronal profiles was significantly increased following capsaicin injection (48.8+/-4.8%) compared to the vehicle injection (23.8+/-5.1%) in superficial laminae on the ipsilateral side in lumbosacral spinal cord (P<0.05). However, when the spinal cord was pretreated with AP7 (5 microg) or CNQX (0.2 microg), only 9.1+/-0.6% or 7.1+/-0.8% of GABA-immunoreactive neuronal profiles were stained for Fos following capsaicin injection. The blockade of the capsaicin-evoked Fos staining was dose-dependent. These findings suggest that GABAergic neurons take part in dorsal horn circuits that modulate nociceptive information and that the function of GABAergic neurons following capsaicin injection is partially mediated by NMDA and non-NMDA receptors.

2-Amino-5-phosphonovalerate↗
PubMed2002

Responses of myenteric S neurones to low frequency stimulation of their synaptic inputs.

Previous experiments have shown that prolonged low frequency stimulation of presynaptic inputs causes excitation of AH neurones that considerably outlasts the period of stimulation in the guinea-pig small intestine. The present experiments compare the responses of S neurones (which are motor neurones and interneurones) with responses of AH neurones (intrinsic primary afferent neurones) to low frequency stimulation of synaptic inputs. Neurones in the myenteric plexus of isolated segments of guinea-pig small intestine were recorded from with intracellular microelectrodes. During their impalement, the neurones were filled with a marker dye and they were later processed to reveal their shapes and immunohistochemical properties. One group of neurones, inhibitory motor neurones to the circular muscle, was depolarised by stimulation of synaptic inputs at 1 Hz for 100 s to 4 min. With 4-min trains of stimuli, peak depolarisation was 21+/-2 mV (mean+/-S.E.M.), which was reached at about 110 s. Depolarisation was accompanied by increased excitability; before stimulation, a test intracellular pulse (500 ms) triggered 3 action potentials, at the peak of excitability this reached 16 action potentials. Depolarisation began to decline immediately at the end of stimulation. This contrasts with responses of AH neurones, in which depolarisation persisted after the end of the stimulus (peak depolarisation at 300 s). The excitation and depolarisation of inhibitory motor neurones was blocked by the neurokinin 1 tachykinin receptor antagonist, SR140333 (100 nM), but excitation of AH neurones was not affected. Small or no responses to 1 Hz stimulation were recorded from descending filamentous interneurones, longitudinal muscle motor neurones and excitatory circular muscle motor neurones. In conclusion, this study indicates that sustained slow postsynaptic excitation only occurs in AH neurones, and that one type of S neurones, inhibitory motor neurones to the circular muscle, responds substantially, but not beyond the period of stimulation, to activation of synaptic inputs at 1 Hz. This slow excitatory postsynaptic potential evoked by low frequency stimulation is mediated by tachykinins.

Action Potentials↗
PubMed2003

Dual modulation of gabaergic transmission by metabotropic glutamate receptors in rat ventral tegmental area.

The effects of metabotropic glutamate receptor (mGluR) activation on non-dopamine (putative GABAergic) neurons and inhibitory synaptic transmission in the ventral tegmental area were examined using intracellular recordings from rat midbrain slices. Perfusion of (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD; agonist for group I and II mGluRs), but not L-amino-4-phosphonobutyric acid (L-AP4; agonist for group III mGluRs), produced membrane depolarization (current clamp) and inward current (voltage clamp) in non-dopamine neurons. The t-ACPD-induced depolarization was concentration-dependent (concentration producing 50% maximal depolarization [EC(50)]=6.1+/-2.5 microM), and was blocked by the antagonist (+/-)-alpha-methyl-4-carboxyphenylglycine, but not by tetrodotoxin and ionotropic glutamate-receptor antagonists. The t-ACPD-evoked responses were mimicked comparably by selective group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG). Furthermore, the DHPG-induced depolarization in non-dopamine neurons was greatly reduced by mGluR1-specific antagonist 7(hydroxyimino)cyclopropachromen-1a-carboxylate ethyl ester. When recorded in dopamine neurons, the frequency of spontaneous GABA(A) receptor-mediated inhibitory postsynaptic potentials was increased by t-ACPD but not L-AP4. However, the amplitude of evoked inhibitory postsynaptic currents in dopamine neurons was reduced by all three group mGluR agonists. These results reveal a dual modulation of mGLuR activation on inhibitory transmission in midbrain ventral tegmental area: enhancing putative GABAergic neuronal excitability and thus potentiating tonic inhibitory synaptic transmission while reducing evoked synaptic transmission at inhibitory terminals.

Anesthetics, Local↗
PubMed1985

[Lumbar cord potentials evoked by stimulation of the nerves of the lower limb in man].

Lumbar cord potentials evoked by electrical stimulation of the posterior tibial and sural nerves at the ankle were recorded with monopolar epidural electrodes, at T11-T12 level in 20 subjects and were compared with surface recorded potentials. Two quadriplegic patients with spinal section were included in this group. Curare was given in two cases. Xylocaine block of peripheral nerve was carried out in 4 cases. Double shock study was done in 5 cases. The lumbar cord evoked potentials show two successive components: a 'primary' negative-positive spike response with a latency of 19-35 msec, and the 'secondary' waves with latencies up to 200 msec. The 'primary' response is mainly produced by the afferent volley in the fibres of the dorsal roots and of their intramedullary prolongations. There is no evidence which suggests that it is correlated with presynaptic inhibition. The secondary components may be divided into the early and the late waves. The early waves (40-90 msec) are related to the polysynaptic activities from the afferent fibres of small diameters. The late waves are under the influence of supraspinal mechanism and may be related to long-loop reflexes. The clinical implications of these evoked potentials are discussed.

Adult↗
PubMed1998

Effects of chronic opioid dependence and HIV-1 infection on pattern shift visual evoked potentials.

The goal of the present study was to examine the effects of opioid dependence, alone and in combination with asymptomatic HIV-1 infection, on the pattern shift visual evoked potential (PSVEP). For this purpose, three groups of patients were evaluated, including patients characterized by: (1) a past history (2-4 months abstinent) of DSM-IIIR opioid dependence (i.e. in partial remission); (2) a recent history (7 days abstinent) of opioid dependence with ongoing methadone maintenance; and (3) a recent history of opioid dependence, ongoing methadone maintenance, and asymptomatic HIV-1 infection. A group of healthy, non-drug dependent volunteers was also evaluated. Analyses revealed no PSVEP differences between patients with a past history of opioid dependence and healthy volunteers. There were also no PSVEP differences between methadone-maintained patients with or without HIV-1 infection. Collectively, however, the two methadone maintenance groups exhibited significant delays in the N75 and P100 components of the PSVEP relative to the other two groups. The delay in N75 latency was strongly correlated with self-reported years of heroin abuse, but not with years of cocaine, alcohol, or other drug abuse. These results are interpreted as reflecting an adverse effect of chronic opioid dependence on neural transmission within primary visual areas of the brain.

Adult↗
PubMed1998

Long-term hearing status after radiotherapy for nasopharyngeal carcinoma.

This paper evaluates the hearing status in the long-term, of patients who have had radiotherapy for nasopharyngeal carcinoma (NPC) and also discusses the hearing losses from a disability point of view, which takes into account binaural hearing. Forty patients who have had NPC successfully treated by a single radical course of radiotherapy of 70-80 Gy were studied at 2-12 years (mean 6.2 years) after radiotherapy. Each patient was examined clinically and with a pure-tone audiogram. Averaged hearing thresholds over 0.5, 1.0, 2.0 and 4.0 kHz were evaluated and a value > 30 dB was considered abnormal. The findings were compared with age-matched controls. The median hearing threshold for each ear in NPC patients was found to be 31.9 dB (range 10.0-86.3 dB) and that for controls 17.5 dB (7.5-38.8 dB) (P < 0.0005, Wilcoxon's matched pairs test). In NPC patients, 44 ears (55.0%) had abnormal hearing, of which 17 (21.3%), 5 (6.3%) and 22 (27.5%) ears had predominantly sensori-neural, conductive and mixed hearing losses, respectively. Nineteen ears had middle ear effusions, accounting for the majority of mixed and conductive hearing losses. In terms of individual patients, 8 (20.0%) and 18 (45.0%) patients had abnormal hearing in one year (monaural hearing disability) and both ears (binaural hearing disability), respectively. In conclusion, a substantial proportion of patients who have had radiotherapy for NPC, have hearing disability in the long-term, as compared to normal controls.

Adult↗
PubMed2000

The pharmacology of local anesthetics.

The pharmacology of local anesthetics is an integration of the basic physiology of excitable cells and the mechanism by which local anesthetics are capable of interrupting conduction of neural messages. The common characteristics of the molecules with local anesthetic action have been identified and can explain the properties of the agents. These same chemical characteristics also explain toxicity of these agents and differences that exist between local anesthetics with similar structure.

Anesthetics, Local↗
PubMed2001

Quantal size is dependent on stimulation frequency and calcium entry in calf chromaffin cells.

To what extent the quantal hypothesis of transmitter release applies to dense-core vesicle (DCV) secretion is unknown. We determined the characteristics of individual secretory events in calf chromaffin cells using catecholamine amperometry combined with different patterns of stimulation. Raising the frequency of action potential trains from 0.25-10 Hz in 2 mM [Ca(2+)]o or [Ca(2+)]o from 0.25-7 mM at 7 Hz elevated the amount released per event (quantal size). With increased stimulation, quantal size rose continuously, not abruptly, suggesting that release efficiency from a single population of DCVs rather than recruitment of different-sized vesicles contributed to the effect. These results suggest that catecholamine secretion does not conform to the quantal model. Inhibition of rapid endocytosis damped secretion in successive episodes, implying an essential role for this process in the recycling of vesicles needed for continuous secretion.

Action Potentials↗
PubMed2003

Glial cells maintain synaptic structure and function and promote development of the neuromuscular junction in vivo.

To investigate the in vivo role of glial cells in synaptic function, maintenance, and development, we have developed an approach to selectively ablate perisynaptic Schwann cells (PSCs), the glial cells at the neuromuscular junction (NMJ), en masse from live frog muscles. In adults, following acute PSC ablation, synaptic structure and function were not altered. However, 1 week after PSC ablation, presynaptic function decreased by approximately half, while postsynaptic function was unchanged. Retraction of nerve terminals increased over 10-fold at PSC-ablated NMJs. Furthermore, nerve-evoked muscle twitch tension was reduced. In tadpoles, repeated in vivo observations revealed that PSC processes lead nerve terminal growth. In the absence of PSCs, growth and addition of synapses was dramatically reduced, and existing synapses underwent widespread retraction. Our findings provide in vivo evidence that glial cells maintain presynaptic structure and function at adult synapses and are vital for the growth and stability of developing synapses.

Animals↗
PubMed2004

Cortical excitability in neuroleptic-naive first-episode schizophrenic patients.

Transcranial magnetic stimulation (TMS) provides an intriguing in vivo method to investigate motor cortex excitability in men. This offers new insights into the neurophysiological basis of neuropsychiatric diseases. Earlier TMS studies in patients with schizophrenia revealed inconsistent results, probably due to major confounding variables like state of medication and stage of illness. To control for these effects, we studied two TMS paradigms in 21 drug-naive first-episode schizophrenic patients and 21 age- and sex-matched healthy controls. The patient group demonstrated a significant lower resting motor threshold as compared with healthy controls, whereas TMS paradigms of intracortical inhibition and intracortical facilitation failed to show significant differences between patients and controls. This pattern of TMS parameters is similar to that obtained in healthy volunteers investigated under increasing doses of ketamine, a central acting drug known to produce psychosis-like effects. In agreement with recent results of functional imaging, our neurophysiological findings suggest that drug-induced and naturally occurring psychosis may share a common pathway, which may base on dysfunctional glutamatergic mechanisms.

Adult↗
PubMedDate not supplied

Presynaptic selection of afferent inflow in the spinal cord.

The synaptic effectiveness of sensory fibers ending in the spinal cord of vertebrates can be centrally controlled by means of specific sets of GABAergic interneurons that make axo-axonic synapses with the terminal arborizations of the afferent fibers. In the steady state, the intracellular concentration of chloride ions in these terminals is higher than that predicted from a passive distribution, because of an active transport mechanism. Following the release of GABA by spinal interneurons and activation of GABA(A) receptors in the afferent terminals, there is an outwardly directed efflux of chloride ions that produces primary afferent depolarization (PAD) and reduces transmitter release (presynaptic inhibition). Studies made by intrafiber recording of PAD, or by measuring changes in the intraspinal threshold of single afferent terminals (which is reduced during PAD), have further indicated that muscle and cutaneous afferents have distinctive, but modifiable PAD patterns in response to segmental and descending stimuli. This has suggested that PAD and presynaptic inhibition in the various types of afferents is mediated by separate sets of last-order GABAergic interneurons. Direct activation, by means of intraspinal microstimulation, of single or small groups of last-order PAD-mediating interneurons shows that the monosynaptic PAD elicited in Ia and Ib afferents can remain confined to some sets of the intraspinal collaterals and not spread to nearby collaterals. The local character of PAD allows cutaneous and descending inputs to selectively inhibit the PAD of segmental and ascending intraspinal collaterals of individual muscle spindle afferents. It thus seems that the intraspinal branches of the sensory fibers are not hard wired routes that diverge excitation to spinal neurons, but are instead dynamic pathways that can be centrally controlled to address information to selected neuronal targets. This feature appears to play an important role in the selection of information flow in muscle spindles that occurs at the onset of voluntary contractions in humans.

Animals↗
PubMed2002

An experimental system for a heterotopic pain stimulation study in humans.

So far heterotopic pain stimulation study has been performed in humans. Many studies have examined changes in subjective pain threshold and nociceptive somatic reflex. However, there are few studies using somatosensory evoked potentials (SEPs) for heterotopic pain stimulation study. Here we describe a new experimental system for a heterotopic pain stimulation study in humans. This system consists of three subsystems including the electrical test stimulation for teeth, the recording of SEP induced by electrical tooth stimulation and conditioning nerve stimulation. The preliminary experiment performed in eight healthy subjects indicated that the electrical test stimulation subsystem with the SEP recording subsystem is also very well indicated for subjective and objective pain evaluation, including VAS estimation and the amplitude of the SEP late component induced by electrical tooth stimulation. Under the experimental system in the present study, electrical median nerve stimulation as conditioning stimulation significantly decreased both the SEP amplitude induced by electrical tooth simulation and subjective pain expressed by the VAS. These results revealed that our experimental system works well and it is very suitable and useful for the study of the pain mechanism under heterotopic stimulation in humans.

Afferent Pathways↗
PubMed2001

Impaired visual function in glaucoma.

OBJECTIVE: This work aims to evaluate whether glaucomatous visual field defects could be related to an impaired retinal function, to a delayed neural conduction in postretinal visual pathways, or both. METHODS: Visual field by Humphrey perimeter (central 24-2 threshold test) and simultaneous recordings of visual evoked potential (VEP) and pattern electroretinogram (PERG) were assessed in 21 subjects with open angle glaucoma (POAG) and in 15 age-matched controls (C). RESULTS: VEP: in POAG eyes we found P100 latency significantly (P<0.01) delayed when compared with controls and correlated with mean deviation (index of global visual field damage, MD) of 24-2 Humphrey perimetry (P<0.001); the P100 amplitudes were significantly (P<0.01) lower in POAG eyes than in control eyes and correlated with MD (P<0.001). PERG: POAG eyes showed P50 latency significantly (P<0.01) delayed when compared with controls and correlated with MD (P=0.002); the P50 and N95 amplitudes were significantly (P<0.01) lower in POAG than in control eyes and correlated with MD (P50: P=0.006; N95: P=0.002). Retinocortical time (RCT: difference between VEP P100 and PERG P50 latencies) and latency window (LW: difference between VEP N75 and PERG P50 latencies) were significantly (P<0.01) longer in POAG eyes than in control eyes and correlated with MD (RCT: P<0.001; LW: P<0.001). No significant correlations (P>0.05) were found between electrophysiological parameters and the corrected pattern standard deviation (index of localized visual field damage) of 24-2 Humphrey perimetry. CONCLUSION: In patients with open angle glaucoma the reduction of the index of global visual field damage (MD) could be ascribed to two sources of functional impairment: one retinal (impaired PERG) and one postretinal (delayed RCT and LW). In the postretinal impairment, a postsynaptic degeneration at the level of the lateral geniculate nucleus could be suggested.

Electroretinography↗
PubMed2003

Rapid reversible changes to multiple levels of the human somatosensory system following the cessation of repetitive contractions: a somatosensory evoked potential study.

OBJECTIVE: Numerous somatosensory evoked potential (SEP) studies have provided clear evidence that during repetitive voluntary movement, the transmission of somatosensory afferent information is attenuated. The objective of this work was to determine if this gating phenomenon could persist beyond the period of repetitive movement. METHODS: We recorded spinal, brainstem, and cortical SEPs to median nerve stimulation before and immediately after a modified 20 min repetitive typing task that did not involve the thenar muscles. RESULTS: There were significant decreases in pre-central cortical and subcortical SEP amplitudes for several minutes following task cessation. CONCLUSIONS: These results demonstrate the persistence of the gating phenomenon beyond the cessation of the actual repetitive movement. They also indicate that plastic changes do occur in cortical and subcortical components of the somatosensory system, following voluntary repetitive contractions. SIGNIFICANCE: The persistence of changes in somatosensory processing beyond the period of repetitive activity may be relevant to the initiation of overuse injuries.

Adult↗