We recorded somatosensory evoked magnetic fields (SEFs) over the hand area of the primary sensorimotor cortex (SMI) in 6 healthy adults in 2 sets of experiments to study interaction of afferent impulses. In experiment 1, SEFs were elicited by contralateral median nerve (MC) stimuli presented alone and 40 msec after a conditioning stimulus to the contralateral ulnar (UC), ipsilateral median (MI) or contralateral tibial (TC) nerve. N20m, P30m and P60m deflections to MC stimulation were markedly attenuated by preceding UC stimulation whereas N40m was enhanced, and a novel P80m emerged. In contrast, MI or TC stimulation did not affect the responses to MC. In experiment 2, the time course of recovery of N20m to median nerve stimuli was studied after stimulation of the adjacent ulnar and of the same median nerve. The recovery curves were similar for both conditioning stimuli with nearly full recovery of N20m at 120 msec. The results indicate marked interaction of impulses from ipsilateral median and ulnar nerves in human SMI, but no evidence was found of interaction from the two hands or from ipsilateral hand and foot.

Although involvement of the frontoparietal regions in visually guided saccade and visuospatial attention has been established, functional difference of the frontal and parietal regions suggested in neuropsychological observations and lesion studies in animals has not been explicitly supported by functional imaging studies. Considering a possible disadvantage of cognitive subtraction in an interregional comparison, we directly compared the time course of BOLD signal changes across regions. Normal subjects performed a modified version of a memory-guided saccade task in which saccade was performed both during encoding and execution phases. In addition, the delay period was fixed and the peripheral target was presented also during the execution phase together with distracters. Therefore, visuospatial representation was likely maintained in the sensory domain during the delay phase. A principal component analysis on the time-course data separated the 20 activated areas into three groups, which largely coincided with the cerebral lobes. The frontal group included the putative human FEF and SEF, and the parietal group PEF. The frontal and occipital groups exhibited the time course of activation with two peaks corresponding to neural responses during the encoding and execution phases, and the parietal group exhibited a single-humped activation pattern corresponding to neural activity during the delay phase. The results suggest that the frontal regions are more associated with the execution of saccade, and the parietal regions with visuospatial representation, presumably in the sensory domain.

Most of what we know about the neural control of gaze comes from experiments in head-fixed animals, but several "head-free" studies have suggested that fixing the head dramatically alters the apparent gaze command. We directly investigated this issue by quantitatively comparing head-fixed and head-free gaze trajectories evoked by electrically stimulating 52 sites in the superior colliculus (SC) of two monkeys and 23 sites in the supplementary eye fields (SEF) of two other monkeys. We found that head movements made a significant contribution to gaze shifts evoked from both neural structures. In the majority of the stimulated sites, average gaze amplitude was significantly larger and individual gaze trajectories were significantly less convergent in space with the head free to move. Our results are consistent with the hypothesis that head-fixed stimulation only reveals the oculomotor component of the gaze shift, not the true, planned goal of the movement. One implication of this finding is that when comparing stimulation data against popular gaze control models, freeing the head shifts the apparent coding of gaze away from a "spatial code" toward a simpler visual model in the SC and toward an eye-centered or fixed-vector model representation in the SEF.

Memory-guided saccades, made to a remembered location to which gaze was directed before a passive body rotation (i.e. with a vestibular input), were electro-oculographically recorded in 24 patients with various cortical lesions and in 18 control subjects. Anticipation and latency, direction errors and accuracy of the first saccade, stability of eye position in darkness and final eye position were quantified. Patients were divided into small groups, each with lesions affecting one of the following cortical areas: left or right frontal eye field (FEF), left or right prefrontal cortex (area 46 of Brodmann) (PFC), left supplementary eye field (SEF), left or right posterior parietal cortex (PPC) and right parieto-temporal cortex (PTC). There were some abnormalities in the results of the right FEF group, concerning anticipation, direction errors and latency of the first saccade, but no abnormality in the accuracy of the first saccade or of the final eye position. Results in the left FEF group were normal. Accuracy of the first saccade was impaired in the SEF group, bilaterally. Final eye position was also inaccurate in the SEF group. In both PFC groups, significant and, in general, bilateral abnormalities existed for all tested parameters. Accuracy of the first saccade was impaired in the PTC group, leftwards. In contrast, the results in both PPC groups were not significantly different from those of control subjects. Our results suggest that (i) the PFC is involved in the memorization of saccade goals probably encoded in spatiotopic coordinates; (ii) the SEF, but not the FEF, is involved in the control of accuracy of these vestibular-derived goal-directed saccades; (iii) the PTC (i.e. the vestibular cortex), but not the PPC, is involved in the control of such saccades. Therefore, a cortical network different from that involved in the control of memory-guided saccades made to visual targets, with only the PFC in common, could control vestibular-derived goal-directed saccades.

The feasibility of using spectral edge frequency (SEF) as a single quantitative measure of the maturation of electrocortical activity is demonstrated in a large number of fetal lambs studied throughout the 3rd trimester. A total of 43 electrocortical recordings obtained from 23 fetal lambs ranging from 116-140 d were subjected to power spectral analysis using the fast Fourier transform. Spectral edge frequency was calculated as the frequency below which 90% of the power resides. The SEF was found to be highly sensitive in identifying the transition between high-voltage slow-activity and low-voltage fast-activity electrocortical activity. By 125 d, the distribution of SEF clearly showed two distinct populations, a low SEF with peak values ranging from 3-9 Hz; and a high SEF (SEFH) with values ranging from 13-23 Hz. Increase in gestational age was associated with a progressive increase in SEFH, which can be described by the linear function (SEF = 0.53GA-51.3). This progressive increase in SEFH reflects the gradual acquisition of faster frequencies. In contrast, low SEF declined with age before 130 d, but then stabilized at 4 Hz throughout the rest of gestation. As a result, there was a gradual increase in the separation between SEFH and low SEF as a function of gestational age.

This study investigated whether the neuronal activity of a cortical area involved in the control of eye fixation is affected by the covert orienting of attention. We recorded single-unit activity from the supplementary eye field (SEF) of two macaque monkeys performing fixation and peripheral-attention tasks. Ninety-nine out of four hundred and fifteen cells were related to eye movements. The other neurons showed relationship with postural adjustments, and arm and ear movements. Fifty-five neurons were active during fixation (fixation cells) and 44 discharged in relation to saccades. The experiments reported here primarily concern the fixation cells. The activity of 64% (35/55) of fixation cells started with the onset of visual stimulus, before the visual input reached the fovea, and continued during active fixation. The activity of 27% (15/55) of fixation cells started with the onset of fixation. The activity of 9% (5/55) of fixation cells modified their timing trial by trial. Sixty-four percent of the fixation cells (35/55) were position-dependent, showing a selective spatial field of activity, 36% (20/55) were position-independent and characterized by a full spatial field. None of the 55 cells showed a visual receptive field. We tested both types of fixation cells by means of a peripheral attention task. When attention was oriented peripherally toward a target located in the selective spatial field, the cells discharged as if the gaze was held toward it. When attention was oriented peripherally toward a target, lying outside the selective spatial field the cells were inactive as if gaze was held in that position. These results suggest that the supplementary eye field neurons may code for oriented attention in space and might be involved in the preparation of motor action.

Lundberg (or B) waves, defined as repetitive changes in intracranial pressure (ICP) occurring at frequencies of 0.5 to 2 waves/min, have been attributed to cerebral blood flow fluctuations induced by central nervous system pace-makers or cerebral pressure autoregulation. We prospectively recorded and digitalized at a frequency rate of 10 Hz (AcqKnowledge software) the following parameters in 6 brain injured patients: mean arterial pressure, heart rate, ICP, mean flow velocity of the middle cerebral artery (MFVMCA) (transcranial Doppler WAKI) and left and right spectral edge frequency (SEFl, SEFr) of continuous electroencephalogram (EEG) recordings (Philips technologies). All patients were sedated using a combination of sufentanil and midazolam and mechanically ventilated. Cerebral electrical activity (oscillations of SEF at a mean frequency of 26+/-9 mHz) and MFVMCA fluctuations were found strongly correlated with the intracranial Lundberg B waves (mean frequency 23+/-7 mHz). These result support the existence of a neuropacemaker at the origin of the Lundberg B waves. The change in cerebral electrical activity, resulting from cerebral pacemakers, could increase cerebral metabolic rate of oxygen (CMRO2) and thus lead to an increase in cerebral blood flow and secondarily of ICP through a change in cerebral blood volume.

BACKGROUND

SPRED1 and 2 are key negative regulators of MAPK signalling in mammalian cells. Here, we investigate the expression and functional role of SPREDs in prostate cancer.

METHODS

A transcriptome bank of microdissected grade-specific primary cancers was constructed and interrogated for transcript expression of prostate cancer genes, known negative signalling regulators as well as SPRED1 and 2. The effect of SPRED2 manipulation was tested in in vitro assays.

RESULTS

In a panel of 5 benign glands and 15 tumours, we observed concomitant downregulation of the negative regulators SEF and DUSP1 in tumours with increasing Gleason grade. Profiling in the same cohorts revealed downregulation of SPRED2 mRNA in tumours compared with benign glands (P<0.05). By contrast, SPRED1 expression remained unchanged. This observation was further validated in two additional separate cohorts of microdissected tumours (total of n=10 benign and n=58 tumours) with specific downregulation of SPRED2 particularly in higher grade tumours. In functional assays, SPRED2 overexpression reduced ERK phosphorylation and inhibited prostate cancer cell proliferation and migration in response to different growth factors and full-media stimulation (P<0.001). Conversely, SPRED2 suppression by siRNA enhanced the mitogenic response to growth factors and full media (P<0.001).

CONCLUSIONS

These data suggest first evidence that SPRED2 is downregulated in prostate cancer and warrants further investigation as a potential tumour-suppressor gene.

Oral drug delivery offers an attractive method of needle-free drug administration. Unfortunately, oral delivery is often hampered by the poor permeability of drugs across the intestinal epithelium. Although several single chemical permeation enhancers have been shown to alleviate permeability difficulties, this often occurs at the expense of safety. This in vitro study demonstrates the use of binary and ternary combinations of permeation enhancers to create synergistic enhancer formulations (SEFs) that offer a high level of potency while inducing very little toxicity in Caco-2 cells. Although relatively rare in the explored formulation space, SEFs were abundant enough to significantly increase the repertoire of permeation enhancers that are safe and effective in vitro. The most promising enhancers from the binary study led to easily identifiable ternary SEFs, thus increasing the efficiency of the discovery process. Some of the best performers of the study included binary combinations of hexylamine and chembetaine and ternary combinations of sodium laureth sulfate, decyltrimethyl ammonium bromide, and chembetaine, all at a total concentration of 0.1% (w/v). Furthermore, several SEFs were shown to be capable of increasing mannitol and 70 kDa dextran permeability across Caco-2 monolayers 15- and 8-fold, respectively. These results encourage further exploration of several leading formulations for in vivo applications in oral drug delivery.

The "gating" effects caused by active finger movements on somatosensory evoked magnetic fields (SEFs) following stimulation of the median nerve were examined in normal subjects. The effects of the interfering stimulus were best demonstrated by subtracting the "interference" wave forms from the "control" wave forms to derive the "difference" wave form. The short-latency cortical deflections, N20m-P20m, P30m-N30m and P25m-N35m were significantly attenuated with no latency changes. In contrast, the following middle-latency deflections, the N40m-P40m and the P60m-N60m were clearly changed in terms of latency and duration by the interference. The D30m-U30m and the U60m-D60m in the "difference" wave form were derived from these interference changes. It is considered that the gating effects on all deflections took place in the hemisphere contralateral to the stimulated median nerve, because all of the equivalent current dipoles (ECDs) of the short- and the middle-latency deflections in the "control", "interference" and "difference" wave forms were located there. The gating effects on the short-latency deflections were suggested to be due to the interactions between the neurons in areas 1 and 3b, which were activated by sensory inputs from cutaneous mechanoreceptors, and the neurons in area 3a which were activated by sensory inputs from the muscle spindles. The gating effects on the middle-latency deflections may mainly be due to the excitations of neurons in area 4 caused by either continuous movement-related activities or by sensory inputs spreading from the sensory cortex.

Chickens were immunised with a preparation of purified 14-kDa fimbriae of Salmonella serotype Enteritidis (SEF 14) to raise egg-yolk antibodies for protection trials in mice against subsequent challenge-exposure with the homologous strain of Enteritidis. A pronounced specificity of egg-yolk antibodies against the 14-kDa fimbrial antigen was demonstrated by Western blotting analysis. Passive antibody protection was evaluated in a mouse model of experimental salmonellosis: 79 mice (CD 1 strain) were challenged orally with 2 x 10(10) cfu of Enteritidis. Test mice treated with SEF-14 antibodies (titre = 128) had a survival rate of 77.8% compared to 32% survival in control mice fed normal egg-yolk antibodies (titre < 10) (p < 0.01). In-vitro adhesion of Enteritidis to mouse intestinal epithelial cells was reduced by anti-fimbrial antibodies. An indirect immunofluorescence method demonstrated the localisation of Enteritidis along the villous margins of the small intestine of control mice, whereas in test mice adherent bacteria were not detected. Results suggest that 14-kDa fimbriae may influence, enhance or contribute to the overall adhesive properties of Enteritidis and that egg-yolk antibodies directed against these fimbriae may have played a substantial role in protection, possibly by minimising bacterial colonisation and invasion during the early stages of infection.

The involvement of type 1 fimbriae in colonisation of the rat gastrointestinal tract in vivo was investigated with Salmonella enterica serotype Enteritidis LA5 and a mutant of LA5 denoted EAV3 unable to elaborate type 1 fimbriae (SEF 21). Rats were given a single dose of LA5 or EAV3 or a 1:1 mixture of both. LA5 was found in higher numbers in the stomach and small intestine than EAV3 at 6 h after infection with a single strain, but not after 6 days. LA5 did not out-compete EAV3 when the strains were administered together. Indeed, after 6 and 21 days, EAV3 was found in the distal small intestine and large intestine in far higher numbers than LA5. These findings suggest that SEF 21 have an important role(s) in the early stages of infection in vivo. However, SEF 21 expression may disadvantage the pathogen in the longer term as indicated by EAV3 out-competing LA5 in the gut at 21 days.

BACKGROUND

The generation of saccades is influenced by the level of "preparatory set activity" in cortical oculomotor areas. This preparatory activity can be examined using the gap-paradigm in which a temporal gap is introduced between the disappearance of a central fixation target and the appearance of an eccentric target.

METHODS

Ten healthy subjects made horizontal pro- or antisaccades in response to lateralized cues after a gap period of 200 ms. Single-pulse transcranial magnetic stimulation (TMS) was applied to the dorsolateral prefrontal cortex (DLPFC), frontal eye field (FEF), or supplementary eye field (SEF) of the right hemisphere 100 or 200 ms after the disappearance of the fixation point. Saccade latencies were measured to probe the disruptive effect of TMS on saccade preparation. In six individuals, we gave realistic sham TMS during the gap period to mimic auditory and somatosensory stimulation without stimulating the cortex.

RESULTS

TMS to DLPFC, FEF, or SEF increased the latencies of contraversive pro- and antisaccades. This TMS-induced delay of saccade initiation was particularly evident in conditions with a relatively high level of preparatory set activity: The increase in saccade latency was more pronounced at the end of the gap period and when participants prepared for prosaccades rather than antisaccades. Although the "lesion effect" of TMS was stronger with prefrontal TMS, TMS to FEF or SEF also interfered with the initiation of saccades. The delay in saccade onset induced by real TMS was not caused by non-specific effects because sham stimulation shortened the latencies of contra- and ipsiversive anti-saccades, presumably due to intersensory facilitation.

CONCLUSIONS

Our results are compatible with the view that the "preparatory set" for contraversive saccades is represented in a distributed cortical network, including the contralateral DLPFC, FEF and SEF.

Enterotoxin production by strains of Staphylococcus aureus isolated from clinical specimens of human and animal origin and from healthy human carriers was investigated. All nine patients admitted to hospital with symptoms of toxic shock syndrome (TSS) yielded enterotoxin-producing strains of S. aureus. Eight of these produced staphylococcal enterotoxin F (SEF). A significantly smaller proportion of strains (42% of 50 strains tested) isolated from other clinical specimens of hospitalized patients produced SEF. Production of SEF by strains isolated from clinical specimens of animal origin (48 strains) was not observed. Twenty-nine per cent of 24 S. aureus strains isolated from noses of hospital staff produced SEF. This result was not significantly different from that obtained from strains isolated from clinical specimens other than TSS. A similar percentage of strains isolated from healthy human carriers outside hospital produced SEF (25% of 24 strains tested). The results indicated that enterotoxin production, especially that of SEF, is associated with S. aureus isolated from patients suspected of TSS. There was no indication of an association between S. aureus isolated from other staphylococcal infections and SEF production. All strains were phage typed and 79% of the strains belonging to the international phage-group I produced SEF. All strains lysed by phage 187 were found to produce SEF.

Cortical processing of passive finger movement was assessed magnetoencephalographically in 12 healthy volunteers and compared with somatosensory evoked magnetic fields (SEF) following tactile stimulation. A new device comprising a clamp-like digit holder facilitated bilateral guidance of the briskly elevated index finger. Both passive movement and tactile stimulation induced activation of the contralateral primary somatosensory (SI) cortex, indicated by six SEF deflections with inter-individually rather consistent peak latencies of 20-230 ms following proprioceptive and 20-300 ms following tactile stimulation. SEF responses to the two stimulus modalities clearly differed with regard to peak latencies, amplitudes and orientations of equivalent current dipoles (ECDs). The strength and orientation of proprioception-related ECDs suggested sequential activation of SI generators, with possible involvement of areas 3a and/or 2 at around 20 ms, area 4 at approximate peak latencies of 65 and 100 ms and area 3b between 150 to 230 ms. Passive movement elicited additional activation of cortical regions outside SI, including the bilateral perisylvian regions and the contralateral cingulate gyrus at latencies of 40-470 and 150-500 ms respectively. The study provides new results with respect to the spatiotemporal analysis of proprioception-related cortical processing and may contribute to a better understanding of the modality-specific organization of the human somatosensory cortex.

We had previously identified a distal regulatory element (DRE) in the mouse serum amyloid A3 (SAA3) promoter that functions as a cytokine-inducible transcription enhancer. Within this DRE, three functional elements interact with CCAAT/enhancer-binding protein (C/EBP) and SAA3 enhancer factor (SEF) transcription factors. In this study, we show that cotransfection of the SEF expression plasmid with an SAA3/luciferase reporter resulted in 3-5-fold activation of the SAA3 promoter. When SEF-transfected cells were further stimulated with conditioned medium or interleukin-1, SAA3 promoter activity was dramatically increased, suggesting that SEF may cooperate functionally with other interleukin-1-inducible transcription factors to synergistically up-regulate SAA3 gene transcription. Indeed, cotransfection of SEF and NFkappaBp65 expression DNAs resulted in synergistic activation of the SAA3 promoter. Intriguingly, no consensus NFkappaB-binding site was found in the SAA3 promoter region; rather a putative NFkappaB-binding sequence with 3-base pair mismatches was identified in the DRE. When this sequence was used in an electrophoretic mobility shift assay, it interacted with NFkappaBp50, albeit with binding affinities that were several hundredfold lower than that with the consensus NFkappaB probe. Functional cooperation between SEF and NFkappaB was further strengthened by the finding that SEF and NFkappaB formed stable cytokine-inducible protein-protein complexes. Finally, despite its weak binding, mutation of this NFkappaB-binding site nevertheless dramatically reduced both NFkappaBp65- and cytokine-mediated induction of SAA3 promoter. Therefore, the molecular basis for the functional synergy between SEF and NFkappaB may, in part, be the ability of SEF to recruit NFkappaB through physical interactions that lead to enhancement or stabilization of NFkappaB binding to the SAA3 promoter element.

OBJECTIVE

Our objective was to characterize the effects of sleep stages on tactile somatosensory evoked responses in full-term newborns.

METHODS

Somatosensory evoked potentials (SEPs) and magnetic fields (SEFs) to tactile stimulation of the tip of the index finger and/or thenar eminence were measured from 14 healthy newborns. The stimulus was a gentle tap produced by a moving membrane driven by an air-pressure pulse.

RESULTS

SEPs and SEFs to tactile stimulation of the skin were similar in waveform and latency to SEPs known to be produced by electrical stimulation of the fingertip of neonates. The two most distinguishable positive deflections of SEPs, P1 and P2, within 300 ms of the stimulation, and their magnetic counterparts were clearly smaller in active compared to quiet sleep.

CONCLUSIONS

Our study demonstrates for the first time that it is possible to record SEFs in neonates, and that clear late cortical somatosensory responses are produced by tactile stimulation. In addition, the effect of sleep stage on these responses indicates differences in the processing of the incoming information, at least in the somatosensory modality, in active and quiet sleep.

CONCLUSIONS

Tactile stimulation may be useful as a completely non-invasive technique for studying the physiology of the somatosensory system in neonates. Methodologically, since the effect of sleep stage is profound, one must carefully monitor the sleep stages in studies of event-related responses in newborns, or else this effect may confound the phenomena being studied.

The distribution of supraependymal nerve fibers (SEF) containing serotonin (5-HT) was investigated immunohistochemically in the forebrain of the guinea pig. The highest densities of immunoreactive axons were found in the pars centralis and the inferior horn of the lateral ventricle and also in the superior part of the third ventricle. Because of the special development of the choroid plexus in these ventricular regions, it is suggested that 5-HT SEF might be involved in the regulation of the composition of the cerebrospinal fluid. The ependyma lining the circumventricular organs located in the forebrain, was not observed to receive a significant 5-HT-SEF innervation. In the pituitary gland, a loose but constant network of 5-HT axons, resembling those which course in the anterobasal hypothalamus, arcuate nucleus and internal layer of the median eminence, was observed in the neural lobe. In the epiphysis, immunoreactive 5-HT was detected in all pinealocytes (the entire cell was filled with reaction product) and in fibers running between them.

Super-resolution imaging has recently been utilized to develop a better understanding of the properties of surface-enhanced Raman scattering (SERS) hot spots. SERS hot spots are much smaller than the diffraction limit of light, and therefore, obtaining a clear picture of the enhanced electromagnetic (EM) fields comprising these hot spots is a challenging task. In this Perspective, we discuss recent work applying super-resolution imaging to single-molecule SERS (SM-SERS) of rhodamine 6G (R6G) adsorbed to randomly assembled silver colloidal aggregates, allowing the shape, size, and local enhancement of the hot spots to be imaged with <5 nm resolution. The results are compared with studies applying super-resolution imaging to surface-enhanced fluorescence (SEF) of analytes diffusing into silver nanoparticle hot spots. Both studies show a strong correlation between emission intensity and position, allowing the EM field enhancements of SERS hot spots to be mapped with sub-5 nm resolution.

Smooth-pursuit eye movements are voluntary responses to small slow-moving objects in the fronto-parallel plane. They evolved in primates, who possess high-acuity foveae, to ensure clear vision about the moving target. The primate frontal cortex contains two smooth-pursuit related areas; the caudal part of the frontal eye fields (FEF) and the supplementary eye fields (SEF). Both areas receive vestibular inputs. We review functional differences between the two areas in smooth-pursuit. Most FEF pursuit neurons signal pursuit parameters such as eye velocity and gaze-velocity, and are involved in canceling the vestibulo-ocular reflex by linear addition of vestibular and smooth-pursuit responses. In contrast, gaze-velocity signals are rarely represented in the SEF. Most FEF pursuit neurons receive neck velocity inputs, while discharge modulation during pursuit and trunk-on-head rotation adds linearly. Linear addition also occurs between neck velocity responses and vestibular responses during head-on-trunk rotation in a task-dependent manner. During cross-axis pursuit-vestibular interactions, vestibular signals effectively initiate predictive pursuit eye movements. Most FEF pursuit neurons discharge during the interaction training after the onset of pursuit eye velocity, making their involvement unlikely in the initial stages of generating predictive pursuit. Comparison of representative signals in the two areas and the results of chemical inactivation during a memory-based smooth-pursuit task indicate they have different roles; the SEF plans smooth-pursuit including working memory of motion-direction, whereas the caudal FEF generates motor commands for pursuit eye movements. Patients with idiopathic Parkinson's disease were asked to perform this task, since impaired smooth-pursuit and visual working memory deficit during cognitive tasks have been reported in most patients. Preliminary results suggested specific roles of the basal ganglia in memory-based smooth-pursuit.

This study was designed to determine if induction of anaesthesia with etomidate titrated to an early EEG burst suppression pattern would produce minimal changes in cerebral perfusion pressure, and prevent increases in intracranial pressure (ICP) associated with tracheal intubation. Eight patients, 18-71 yr, with intracranial space-occupying lesions, were studied. In each patient ICP was monitored via a lateral ventriculostomy catheter placed preoperatively. In the operating room, an ECG, a radial arterial line, and a two-channel computerized EEG were placed. Control (awake) measurements of MAP (mmHg), ICP (mmHg), CPP (mmHg), heart rate (HR-bpm), EEG power (picowatts-pW), and spectral edge frequency (SEF, Hz) were obtained. Anaesthesia was induced with etomidate, 0.2 mg.kg-1 iv, followed immediately by an etomidate infusion, 20 mg.min-1, iv, and vecuronium 0.2 mg.kg-1 iv. When early burst suppression was achieved, the etomidate infusion was stopped and tracheal intubation performed. The etomidate dose (bolus plus infusion) required to reach burst suppression was 1.28 +/- 0.11 mg.kg-1. Compared with awake control values (mean +/- SE), the period from induction to burst suppression was associated with a 50% decrease in ICP (22 +/- 1 vs 11 +/- 1 mmHg, P less than 0.01), but there were no changes in MAP, CPP, or HR. The decrease in ICP was maintained during the first 30 sec and the following 60 sec after intubation as MAP and HR remained unchanged. Our results suggest that when etomidate was administered to early burst suppression pattern on EEG, minimal changes in CPP occurred during induction of anaesthesia and a marked reduction in ICP was maintained following tracheal intubation.

OBJECTIVE

To investigate the neural activation in the primary somatosensory cortex (SI) that is induced by capsaicin-evoked secondary Abeta-fiber-mediated hyperalgesia with magnetic source imaging (MSI) in healthy humans.

BACKGROUND

Dynamic mechanical hyperalgesia, i.e. pain to innocuous light touching, is a symptom of painful neuropathies. Animal experiments suggest that alterations in central pain processing occur so that tactile stimuli conveyed in Abeta low threshold mechanoreceptive afferents become capable of activating central pain signalling neurons. A similar state of central sensitization can be experimentally produced with capsaicin.

METHODS

In six individuals the somatosensory evoked magnetic fields (SEFs) induced by non-painful electrical stimulation of Abeta-afferents at the forearm skin were recorded. Capsaicin was injected adjacent to the stimulation site to induce secondary dynamic Abeta-hyperalgesia. Thereafter, the SEFs induced by the identical electrical stimulus applied within the secondary hyperalgesic skin were analyzed. The electrical stimulus was subsequently perceived as painful without changing the stimulus intensity and location. Latencies, anatomical source location and amplitudes of SEFs during both conditions were compared.

RESULTS

Non-painful electrical stimulation of Abeta-afferents induced SEFs in SI at latencies between 20 and 150 ms. Stimulation of Abeta-afferents within the capsaicin-induced secondary hyperalgesic skin induced SEFs at identical latencies and locations as compared with the stimulation of Abeta-afferents within normal skin. The amplitudes, i.e., the magnetic dipole strengths of the SEFs were higher during Abeta-hyperalgesia.

CONCLUSIONS

Acute application of capsaicin produces an increase in the excitability of central neurons, e.g., in SI. This might be due to sensitization of central neurons so that normally innocuous stimuli activate pain signalling neurons or cortical neurons might increase their receptive fields.

OBJECTIVE

To identify changes in the amplitude spectrum of the electroencephalogram (EEG) during a standardized surgical model of nociception in horses.

METHODS

Thirteen entire male horses and ponies referred to Division of Clinical Veterinary Science, Bristol (n = 9) and Department of Clinical Veterinary Medicine (n = 4) for castration.

METHODS

Following pre-anaesthetic medication with acepromazine, anaesthesia was induced with guaiphenesin and thiopental and maintained with halothane in oxygen. The EEG was recorded continuously using subcutaneous needle electrodes. Additional monitoring comprised ECG, arterial blood pressure, blood gas analysis, airway gases, and body temperature. All animals were castrated using a closed technique. The raw EEG was analysed after completion of each investigation and the EEG variables median frequency (F50), spectral edge frequency (SEF) 95% and total amplitude were derived from the spectra using standard techniques. The mean values of EEG variables recorded during a baseline time period (recorded before the start of surgery) and castration of each testicle were compared using analysis of variance for repeated measures.

RESULTS

Total amplitude (Atot) decreased and F50 increased during castration of each testicle compared to the baseline time period [(89.0 +/- 7.8% testicle 1, 87.0 +/- 7.8% testicle 2) and (110.0 +/- 15.0% testicle 1, 109.0 +/- 15.0% testicle 2), respectively]. Changes in SEF 95% were not significant.

CONCLUSIONS

De-synchronization was identified in the EEG during the nociceptive stimulus of castration. The results suggest that an increase in F50 may be a specific marker for nociception in the horse.

CONCLUSIONS

Studies investigating the efficacy of analgesic agents in horses are limited by difficulties in peri-operative pain assessment. This model, using EEG changes associated with nociceptive stimulation, can be used to investigate the anti-nociceptive efficacy of different anaesthetic agents in the horse.

Focal hand dystonia (FHd) is a recalcitrant, disabling movement disorder, characterized by involuntary co-contractions of agonists and antagonists, that can develop in patients who overuse or misuse their hands. The aim of this study was to document clinical neuromusculoskeletal performance and somatosensory responses (magnetoencephalography) in healthy controls and in FHd subjects with mild versus severe hand dystonia. The performance of healthy subjects (n = 17) was significantly better than that of FHd subjects (n =17) on all clinical parameters. Those with mild dystonia (n = 10) demonstrated better musculoskeletal skills, task-specific motor performance, and sensory discrimination, but the performance of sensory and fine motor tasks was slower than that of patients with severe dystonia. In terms of somatosensory evoked field responses (SEFs), FHd subjects demonstrated a significant difference in the location of the hand representation on the x and y axes, lower amplitude of SEFs integrated across latency, and a higher ratio of mean SEF amplitude to latency than the controls. Bilaterally, those with FHd (mild and severe) lacked progressive sequencing of the digits from inferior to superior. On the affected digits, subjects with severe dystonia had a significantly higher ratio of SEF amplitude to latency and a significantly smaller mean volume of the cortical hand representation than those with mild dystonia. Severity of dystonia positively correlated with the ratio of SEF mean amplitude to latency (0.9029 affected, 0.8477 unaffected; p < 0.01). The results of the present study strengthen the evidence that patients with FHd demonstrate signs of somatosensory degradation of the hand that correlates with clinical sensorimotor dysfunction, with characteristics of the de-differentiation varying by the severity of hand dystonia. If these findings represent aberrant learning, then effective rehabilitation must incorporate the principles of neuroplasticity. Training must be individualized to each patient to rebalance the sensorimotor feedback loop and to restore normal fine motor control.