Median and tibial nerve somatosensory evoked potentials: middle-latency components from the vicinity of the secondary somatosensory cortex in humans

The topography of the middle-latency N110 after radial nerve stimulation suggested a generator in SII. To support this hypothesis, we have tried to identify a homologous component in the tibial nerve SEP (somatosensory evoked potential). Evoked potentials following tibial nerve stimulation (motor+sensory threshold) were recorded with 29 electrodes (bandpass 0.5–500 Hz, sampling rate 1000 Hz). For comparison, the median nerve was stimulated at the wrist. Components were identified as peaks in the global field power (GFP). Map series were generated around GFP peaks and amplitudes were measured from electrodes near map maxima. With median nerve stimulation, we recorded a negativity with a maximum in temporal electrode positions and 106±12 ms peak latency (mean±SD), comparable to the N110 following radial nerve stimulation. After tibial nerve stimulation the latency of a component with the same topography was 131±11 ms (N130). Both N110 and N130 were present ipsi- as well as contralaterally. Amplitudes were significantly higher on the contralateral than the ipsilateral scalp for both median (3.1±2.4 μV vs. 1.7±1.6 μV) and tibial nerve (1.9±1.2 μV vs. 0.6+1 μV). The topography of the N130 can be explained by a generator in the vicinity of SII. The latency difference between median and tibial nerve stimulation is related to the longer conduction distance (cf. N20 and P40). The smaller ipsilateral N130 is consistent with the bilateral body representation in SII.     

Visual evoked potentials in response to dichoptic presentation of sinusoidal grating and noise background

Dichoptic stimulation was used in comparison of visual evoked potentials (VEPs) with those obtained with monocular stimulation (recordings made from the occipital area). 16 subjects viewed sinusoidal gratings with the right eye while a visual noise was added via a mirror for the left eye. In presence of the noise, amplitude of the early VEP components' N1, P1b, and the late component P2 decreased, P1a is not changed in presence of the noise, and the late negative wave N2 increased for all spatial frequencies. The effect of noise on the amplitude of VEPs obtained for monocular and dichoptic stimulation was similar. The data suggest that external noise is filtered by the V1 cortical neurons--matched filters for the gratings.     

Scalp-recorded oscillatory potentials evoked by transient pattern-reversal visual stimulation in man

Replicable oscillatory potentials, time-locked to pattern stimuli (9.0° central; counterphase reversal at 2.13 Hz) were dissociated from conventional, broad-band VEPs recorded in healthy volunteers at occipital scalp locations by high-pass digital filtering at 17.0–20.0 Hz. Nine consecutive wavelets were identified with a 56.4 ± 8.4 msec mean latency of the first replicable wavelet and mean peak-to-peak amplitude varying between 0.9 and 2.0 μV. The first 2 wavelets had significantly shorter latencies than wave N70 of unfiltered VEP, whereas the last 2 wavelets had longer latencies than N145. Latency and amplitude values varied as a function of contrast and spatial frequency of the stimulus, with shorter latencies and larger amplitudes at 60–90% contrast level and tuning of amplitude at 5.0 c/deg. All wavelets were correlated with wave P100 of unfiltered VEP, while a correlation with N70 of VEP was observed only for those wavelets with latencies in the range of wave P100. Two patients with documented brain lesions involving the visual system are described as examples of oscillatory responses occurring irrespective of filter bandpass and instead of the expected conventional VEP when the generation of these is interfered with by brain pathology. A substantial cortical contribution to the origin of the oscillatory response is conceivable. It is suggested that the oscillatory response to pattern-reversal stimulation reflects events in the visual system that are parallel to, and partly independent of, the conventional VEP, with potential application in research or for clinical purposes.     

Pharmacological Mechanisms of Cortical Enhancement Induced by the Repetitive Pairing of Visual/Cholinergic Stimulation

Repetitive visual training paired with electrical activation of cholinergic projections to the primary visual cortex (V1) induces long-term enhancement of cortical processing in response to the visual training stimulus. To better determine the receptor subtypes mediating this effect the selective pharmacological blockade of V1 nicotinic (nAChR), M1 and M2 muscarinic (mAChR) or GABAergic A (GABA_AR) receptors was performed during the training session and visual evoked potentials (VEPs) were recorded before and after training. The training session consisted of the exposure of awake, adult rats to an orientation-specific 0.12 CPD grating paired with an electrical stimulation of the basal forebrain for a duration of 1 week for 10 minutes per day. Pharmacological agents were infused intracortically during this period. The post-training VEP amplitude was significantly increased compared to the pre-training values for the trained spatial frequency and to adjacent spatial frequencies up to 0.3 CPD, suggesting a long-term increase of V1 sensitivity. This increase was totally blocked by the nAChR antagonist as well as by an M2 mAChR subtype and GABA_AR antagonist. Moreover, administration of the M2 mAChR antagonist also significantly decreased the amplitude of the control VEPs, suggesting a suppressive effect on cortical responsiveness. However, the M1 mAChR antagonist blocked the increase of the VEP amplitude only for the high spatial frequency (0.3 CPD), suggesting that M1 role was limited to the spread of the enhancement effect to a higher spatial frequency. More generally, all the drugs used did block the VEP increase at 0.3 CPD. Further, use of each of the aforementioned receptor antagonists blocked training-induced changes in gamma and beta band oscillations. These findings demonstrate that visual training coupled with cholinergic stimulation improved perceptual sensitivity by enhancing cortical responsiveness in V1. This enhancement is mainly mediated by nAChRs, M2 mAChRs and GABA_ARs. The M1 mAChR subtype appears to be involved in spreading the enhancement of V1 cortical responsiveness to adjacent neurons.     

Spatial frequency response functions obtained from cat visual evoked potentials

Visual evoked potentials (VEPs) were obtained from the surface of teh cat visual cortex in response to contrast reversing sinusoidal gratings. Gratings of different spatial frequency were presented either separately, using signal averaging to increase the signal-to-noise ratio, or as a spatial frequency sweep, in which spatial frequency was sequentially increased every 5 sec during a 40 sec trial (3.99 Hz) or every 3 sec during a 24 sec trial (6.65 Hz). The second harmonic amplitude- and phase-spatial frequency functions derived from averaging or from sweep trials were similar, indicating that the swept stimulus method can be used to provide a rapid and reliable measure of the VEP-spatial frequency function. Intravenous administration of physostigmine, an acetylcholinesterase inhibitor, evoked a spatial frequency-dependent change in VEP amplitude. At 3.99 Hz, responses to low spatial frequencies were enhanced to a greater extent than were responses to high spatial frequency stimuli. At 6.65 Hz, responses to mid-range spatial frequencies were enhanced to a greater extent than were responses to low and high spatial frequency stimuli. VEP phase at both 3.99 and 6.65 Hz was advanced to a greater degree at the higher spatial frequencies. These results indicate that the swept spatial frequency method may be useful in studying spatial frequency-dependent pharmacological effects on the VEP and support the possibility that pharmacological disruption of the cholinergic visual system can produce such changes.     

Cholinergic Pairing with Visual Activation Results in Long-Term Enhancement of Visual Evoked Potentials

Acetylcholine (ACh) contributes to learning processes by modulating cortical plasticity in terms of intensity of neuronal activity and selectivity properties of cortical neurons. However, it is not known if ACh induces long term effects within the primary visual cortex (V1) that could sustain visual learning mechanisms. In the present study we analyzed visual evoked potentials (VEPs) in V1 of rats during a 4–8 h period after coupling visual stimulation to an intracortical injection of ACh analog carbachol or stimulation of basal forebrain. To clarify the action of ACh on VEP activity in V1, we individually pre-injected muscarinic (scopolamine), nicotinic (mecamylamine), α7 (methyllycaconitine), and NMDA (CPP) receptor antagonists before carbachol infusion. Stimulation of the cholinergic system paired with visual stimulation significantly increased VEP amplitude (56%) during a 6 h period. Pre-treatment with scopolamine, mecamylamine and CPP completely abolished this long-term enhancement, while α7 inhibition induced an instant increase of VEP amplitude. This suggests a role of ACh in facilitating visual stimuli responsiveness through mechanisms comparable to LTP which involve nicotinic and muscarinic receptors with an interaction of NMDA transmission in the visual cortex.     

Neuronal responses to turtle head rotation in vitro

Extracellular recordings were made during vestibular stimulation from an in vitro turtle brain stem in which the temporal bones remained attached. Under visual control, microelectrodes were slowly advanced into the vestibular nucleus (VN) while we rotated the brain and searched for a single isolated unit whose spike activity was modulated by the lateral semicircular canals. In some experiments, responses were shown to be due to stimulation of the lateral canals, either by positioning the brains in forward or backward pitch during horizontal rotation or by plugging the vertical canals with wax. VN neurons usually had low spontaneous activity and rectified sinusoidal responses to sinusoidal stimulation. Spike response histograms were averaged from many stimulus cycles and were then fit to a sine function. The fitted phase and amplitude parameters were plotted relative to stimulus frequency and amplitude. The sample of VN cells were quite heterogeneous. Using stimuli at 1 Hz, however, each cell's response phase was weakly correlated with the slope of the plots of response amplitude versus frequency so that a cell could be categorized as sensitive to velocity or acceleration and as sensitive to ipsiversive or contraversive rotation, depending on whether its phase was near −180°, −90°, 0°, or 90°, and whether the gain exceeded 0.4 spikes/s per °/s. The properties of these VN cells suggest that there is substantial complexity in the vestibular responses at this first site of central vestibular processing. These data are compared to that of other species where such vestibular signals play an important role in oculomotor and spinal reflexes. © 1997 John Wiley & Sons, Inc. J Neurobiol 33: 99–177, 1997     

Biliary transport maximum of tauroursodeoxycholate is twice as high as that of taurocholate in the rat

Biliary excretory transport maximum (Tm) and choleretic efficiency were compared for tauroursodeoxycholate and taurocholate in Wistar male rats. Under a continuous iv infusion of bile salts with a stepwise increase in infusion rate, the Tm of tauroursodeoxycholate was found to be two times higher (2.25±0.07 μmole/min/100 g body weight, n=8, mean±SD) than that of taurocholate (0.97±0.05 μmole/min/100 g body weight, n=14, p<0.001). On the other hand, the amount of bile water obligated by the excretion of 1μmole of tauroursodeoxycholate was significantly lower than that of taurocholate. (4.71±0.08 μl/μmole for tauroursodeoxycholate, vs. 9.27±0.76 μl/μmole for taurocholate, mean±SD, p<0.001). It was concluded that tauroursodeoxycholate can be excreted into the bile in male rats twice as efficiently as taurocholate. Furthermore, the higher efficiency in the choleretic property of ursodeoxycholate previously reported by Dumont et al. appears to be specific to free ursodeoxycholate and not to its taurine conjugate used in the present experiment.     

The effect of binocular stimulation on each component of transient and steady-state VEPs

We recorded the monocular and binocular VEPs to the alternation of sinusoidal gratings in order to evaluate the binocular interaction in each component of transient and steady-state VEPs in 13 normal subjects. Three spatial frequencies (1.3, 2.6 and 5.3 c/deg) with a 90% contrast were used as visual stimuli. The latencies and amplitudes of N70 and P100 of the transient VEPs were measured. The steady-state VEPs were Fourier analyzed, and both the phase and amplitude of the second (2F) and fourth (4F) harmonic responses were obtained. Binocular interaction was influenced by spatial frequency such that a binocular summation or even an inhibition occurred. For the transient VEPs, a binocular summation was more pronounced in the amplitude of N70 than in that of P100 at all spatial frequencies. There were no significant effects of binocular stimulation on latencies of N70 or P100. However, the latencies of N70 and P100 showed different spatial frequency characteristics. For the steady-state VEPs, the amplitude of 2F revealed a binocular summation that was more pronounced at 5.3 c/deg, whereas the 4F amplitude showed binocular inhibition at 2.6 and 5.3 c/deg. The 2F phase showed binocular inhibition at all spatial frequencies, whereas no such inhibition was observed in the 4F phase. These results suggest that individual components of transient and steady-state VEPs are physiologically distinct and may therefore be generated from different neuronal populations in striate cortex.     

Cortical modulation of the transient visual response at thalamic level: a TMS study

The transient visual response of feline dorsal lateral geniculate nucleus (dLGN) cells was studied under control conditions and during the application of repetitive transcranial magnetic stimulation at 1 Hz (rTMS@1Hz) on the primary visual cortex (V1). The results show that rTMS@1Hz modulates the firing mode of Y cells, inducing an increase in burst spikes and a decrease in tonic firing. On the other hand, rTMS@1Hz modifies the spatiotemporal characteristics of receptive fields of X cells, inducing a delay and a decrease of the peak response, and a change of the surround/center amplitude ratio of RF profiles. These results indicate that V1 controls the activity of the visual thalamus in a different way in the X and Y pathways, and that this feedback control is consistent with functional roles associated with each cell type.     

Characterisation of baseline oscillation in congenital nystagmus eye movement recordings

Congenital nystagmus is an ocular–motor disorder that develops in the first few months of life; its pathogenesis is still unknown. Patients affected by congenital nystagmus show continuous, involuntary, rhythmical oscillations of the eyes. Monitoring eye movements, nystagmus main features such as shape, amplitude and frequency, can be extracted and analysed. Previous studies highlighted, in some cases, a much slower and smaller oscillation, which appears added up to the ordinary nystagmus waveform. This sort of baseline oscillation, or slow nystagmus, hinder precise cycle-to-cycle image placement onto the fovea. Such variability of the position may reduce patient visual acuity. This study aims to analyse more extensively eye movements recording including the baseline oscillation and investigate possible relationships between these slow oscillations and nystagmus. Almost 100 eye movement recordings (either infrared-oculographic or electrooculographic), relative to different gaze positions, belonging to 32 congenital nystagmus patients were analysed. The baseline oscillation was assumed sinusoidal; its amplitude and frequency were computed and compared with those of the nystagmus by means of a linear regression analysis. The results showed that baseline oscillations were characterised by an average frequency of 0.36 Hz (SD 0.11 Hz) and an average amplitude of 2.1° (SD 1.6°). It also resulted in a considerable correlation (R² scored 0.78) between nystagmus amplitude and baseline oscillation amplitude; the latter, on average, resulted to be about one-half of the correspondent nystagmus amplitude.     

Low-temperature tolerance of juvenile tarpon <Emphasis Type="Italic">Megalops atlanticus</Emphasis>

The tarpon Megalops atlanticus is a tropical to subtropical species whose pole-ward distribution is thought to be limited by low water temperatures. In the western north Atlantic Ocean juvenile tarpon occur in estuaries of the South Atlantic Bight (SAB) north of Florida near the northern limit of its distribution, but it is currently unknown whether these individuals can survive winter, grow to maturity, and contribute to the adult population. As a first step to determine whether juvenile tarpon can survive winter conditions in the SAB, we conducted laboratory experiments to estimate minimum lethal temperatures of tarpon exposed to 1) ambient fluctuating winter water conditions and 2) a constant rate of temperature decline. Juvenile tarpon exposed to ambient winter water conditions had a mean ± standard deviation (SD) minimum lethal temperature of 13.7 ± 3.4 °C. When exposed to a constant rate of temperature decline (2 °C day^?1), mean ± SD minimum lethal temperature (9.2 ± 0.8 °C) was lower than when tarpon were exposed to ambient fluctuating conditions. A combination of our results with all published data on the cold tolerance of juvenile tarpon resulted in an overall mean ± SD minimum lethal temperature of 12.0 ± 2.8 °C. Based on available long-term temperature records from SAB estuaries, overwinter survival of juvenile tarpon is unlikely in most aquatic habitats (e.g., tidal creeks, flats, open water). Similar to other estuarine transient fishes, juvenile tarpon likely exploit seasonably favorable nursery habitats and then migrate to other locations to overwinter.     

Water velocity dependence of phosphate uptake on a coral-dominated fringing reef flat,La Réunion Island,Indian Ocean

Phosphate uptake (P-uptake) into coral reef communities has been hypothesized to be mass-transfer limited. One method of demonstrating mass-transfer limitation of P-uptake is to show dependence of P-uptake on water velocity. Water velocity across reef flats varies with tides and swell; thus, we measured P-uptake over the entire reef flat on eight different days, representing a range in water velocities. P-uptake was calculated from changes in P concentration of the water column. Changes in P concentration were measured by water sampling at six sites along a 300-m cross-reef transect while simultaneously measuring water velocity. To smooth the variability in phosphate concentrations, peristaltic pumps were used to get time-integrated water samples for 4–6 h at each site. Water velocities were measured in the middle of the transect using an acoustic Doppler current profiler and were averaged to match the time-integrated water sampling. Depth-averaged cross-reef water velocities were 0.031 ± 0.013 m s⁻¹ (mean ± SD), while the root-mean-square water velocities, accounting for oscillatory flow, averaged 3.3 times higher, 0.101 ± 0.021 m s⁻¹ (mean ± SD). Phosphate decreased along all transects. The first-order rate constant for P-uptake (S) was 8.5 ± 2.4 m d⁻¹ (mean ± SD) and increased linearly with root-mean-square water velocity. The Stanton number derived from oscillatory flow, the ratio of the first-order rate constant for P-uptake to the root-mean-square water velocity (S/U _rms), was (9.4 ± 1.2) × 10⁻⁴ (mean ± SD). P-uptake ranged from 0.2 to 1.1 mmol P m⁻² d⁻¹, demonstrating that P-uptake is variable on short time scales and is directly related to P concentration and water velocity.

     

猫外膝体神经元非寻常的方位调谐特性──Ⅱ．在去视皮层猫和视觉剥夺猫（Dark－reared cats）的研究

以移动的正弦光栅作为刺激,用玻璃微电极记录以冰冻法毁损皮层１７、１８、１９区和外侧上雪氏回区后的猫外膝体的单细胞反应,测定了５７９个细胞的方位调谐特性,另外还在视觉剥夺猫外膝体测定了３４４个细胞的方位调谐特性,与正常猫相似,去视以猫和视觉剥夺猫外膝体的少数细胞具有非寻常的方位调谐特性,包括具蝴蝶形调谐曲线的方位调谐特性、双调谐的方位调谐特性和最优方位随刺激空间的不同而变化的方位调谐特性。结果表明外     

Amplitude asymmetry of hemifield pattern reversal VEPs in healthy subjects

The amplitudes of transient and steady-state visual evoked potentials (VEPs) were measured during hemifield stimulation of the left eye in 10 healthy adults. Pattern reversal of a checkerboard was produced at 4 stimulation frequencies: 1, 5, 10 and 15 Hz. The amplitudes of pattern VEPs were evaluated using the paired t test to determine significant differences between right and left hemifields. The transient VEP amplitudes from midoccipital, midparietal, ipsilateral occipital and contralateral occipital electrodes were significantly greater with right hemifield stimulation. The steady-state VEP amplitudes from the midoccipital electrode during 15 Hz stimulation were significantly greater with right hemifield stimulation. Our neurophysiological data may be compatible with neuroanatomical asymmetries of the occipital lobes in humans.     

The role of bronchial epithelial cell apoptosis in the pathogenesis of COPD

There is an increased airway inflammation in the pathogenesis of chronic obstructive pulmonary disease (COPD), and it has been suggested that there may also be problem in the apoptosis and renewal of cells. However, there are limited human airway cell studies, in particular those from larger airways such as bronchi. We cultured primary human bronchial epithelial cells (HBECs) from bronchial explants of smokers (n = 6) without COPD and smokers with COPD (n = 8). Apoptosis was studied by fluorescence activated cell sorting. qRT-PCR was used to assess mRNA expression for proteins involving apoptosis including p21^CIP1/WAF1, p53, caspase-8 and caspase-9. Although there was no difference in the rate of viable cells between cells from smokers and COPDs, the level of early apoptotic cells was significantly increased in COPD cells [mean ± standard error of mean (SEM) = 4.86 ± 3.2 %, p = 0.015] as compared to smokers (mean ± SEM = 2.71 ± 1.62 %). In contrast, the rate of late apoptotic cells was significantly decreased in COPD cells (mean ± SEM = 9.82 ± 5.71 %) comparing to smokers (mean ± SEM = 15.21 ± 5.08 %, p = 0.003). Although expression of mRNA for p21^CIP1/WAF1 and caspase-9 was similar in both groups, p53 and caspase-8 mRNA expression was significantly greater in COPD cells. These findings suggest that HBEC apoptosis is increased in COPD, and that this involves p53 and caspase-8 pathways.     

单眼视觉剥夺猫外膝体神经元的双眼反应特性

采用在位（ｉｎ ｖｉｖｏ） 胞内记录技术,研究了单眼视觉剥夺猫外膝体（ＬＧＮ） 神经元的双眼反应特性（ｂｉｎｏｃｕｌａｒｉｔｙ） , 结果发现单眼剥夺猫外膝体几乎所有的双眼反应神经元都对非优势眼的闪烁光斑刺激有不同程度的反应,并且剥夺层和非剥夺层神经元在反应特性上没有明显差异。但是,与非剥夺层神经元相比,几乎没有剥夺层的神经元能对非优势眼的正弦移动光栅刺激起反应,并受其空间频率的调制。结果提示皮层下外膝体水平上这种双眼反应的某些精细反应性质可能与后天视觉经验的修饰有关,并可能受皮层反馈输入的影响。     

Effects of glutathione S-transferase T1 and M1 deletions on advanced carotid atherosclerosis, oxidative, lipid and inflammatory parameters

Glutathione S-transferases (GSTs) carry out a wide range of functions in cells, such as detoxification of endogenous compounds, removal of reactive oxygen species, and even catalysis of reactions in metabolic pathways beyond detoxification. Based on previous research, GSTM1 and GSTT1 might modify the risk of atherosclerosis. The aim of our study was to analyze the possible association of GSTM1 and GSTT1 gene polymorphisms with the occurrence of carotid plaque (CP); and biochemical parameters of oxidative stress, lipid profile and inflammation, in 346 consecutive patients with advanced atherosclerosis that underwent endarterectomy. A multiplex polymerase chain reaction (PCR) method was used to detect the deletions in GSTM1 and GSTT1 genes in the genomic DNA in 346 patients and 330 controls. The adjusted OR for CP presence (adjusted for age, gender, smoking, hypertension, BMI, HDLC, TG) was 0.24, 95 %CI 0.08–0.7, p < 0.01 for GSTT1 null and 1.13, 95 %CI 0.62–2.07, p = 0.7 for GSTM1 null genotype. We found significantly lower plasma lipoprotein (a) (Lp(a)) levels in GSTT1 null compared to wild-type genotype carriers in patient group (20.68 ± 26.02 mg/dl vs. 40.66 ± 42.89 mg/dl, mean ± SD, p = 0.04). The serum interleukin-6 (IL-6) values were significantly influenced by both GST polymorphisms in patients with CP. Our results, showing the significant reduction of GSTT1 deletions in patients with CP, suggest involvement of GSTs in carotid atherosclerosis. This study shows additional view of the possible role of GSTs in advanced chronic inflammatory disease of vascular system, but the confirmation in a larger studies in different populations are needed.     

猫外膝体神经元非寻常的方位调谐特性──Ⅱ．在去视皮层猫和视觉剥夺猫（Dark－reared cats）的研究

以移动的正弦光栅作为刺激,用玻璃微电极记录以冰冻法毁损皮层１７、１８、１９区和外侧上雪氏回（ＬＳ）区后的猫外膝体的单细胞反应,测定了了５７９个细胞的方位调谐特性．另外还在视觉剥夺猫外膝体测定了３４４个细胞的方位调谐特性．与正常猫相似,去视皮层猫和视觉剥夺猫外膝体的少数细胞（约占１０％）具有非寻常的方位调谐特性,包括具蝴蝶形调谐曲线的方位调谐特性、双调谐（Ｂｉｍｏｄａｌ）的方位调谐特性和最优方位随刺激空间频率的不同而变化的方位调谐特性。结果表明,外膝体的非寻常的方位调谐特性并非主要由皮层下行投射所致,而是主要与先天遗传因素有关。     

Selective and rapid liquid chromatography–mass spectrometry method for the quantification of rofecoxib in pharmacokinetic studies with humans

An easy, rapid and selective method for the determination of rofecoxib in human plasma is presented. The analytical technique is based on reversed-phase high-performance liquid chromatography coupled to atmospheric pressure chemical ionisation mass spectrometry (Finnigan Mat LCQ ion trap). The retention time of rofecoxib was 1.2 min. The method has been validated over a linear range from 1 to 500 μg/l using celecoxib as internal standard. After validation, the method was used to study the pharmacokinetic profile of rofecoxib in 12 healthy volunteers after administration of a single oral dose (12.5 mg). The presented method was sufficient to cover more than 95% of the area under the curve. The pharmacokinetic characteristics (mean±SD) were t_max: 2.4±1.0 h, c_max: 147±34 μg/l, AUC_∞: 2038±581 μg h/l and t_1/2: 11.3±2.1 h.