Global field power helps separate respiratory-related evoked potentials from EMG contamination.

Respiratory-related evoked potentials (RREPs) were stimulated by brief (200-ms) oral pressure pulses (-10 cmH(2)O) applied at the onset of inspiration in 12 subjects. Scalp potentials were measured at 30 sites on a rectangular grid that encompassed the right side of the scalp overlying the somatosensory cortex (SSC). Concurrent and significant masseter EMG (mEMG) activity was evoked by the pressure pulse, and we found correlational evidence for contamination of the RREP by the mEMG. The global field power (GFP) was used to provide a robust, reference-independent measure of SSC activation that provided partial insulation from mEMG contamination. The mean GFP from all subjects, reflective of afferent information from respiratory mechanoreceptors, showed a latency to onset of significant afferent SSC activity of approximately 25 ms. Scalp GFP activity during control experiments (absence of applied pressure) was significant and may reflect ongoing afferent activity from inspiration.     

Reduced respiratory-related evoked activity in subjects with obstructive sleep apnea syndrome.

Midlatency respiratory-related evoked potentials were measured during wakefulness by using a 60-electrode array placed over the cortical region of the scalp. We studied the responses evoked by 200-ms pressure pulses at -5 and -10 cmH(2)O applied at inspiratory onset and during control tests (no pressure applied) in 14 subjects with obstructive sleep apnea syndrome (OSAS) and 18 normal subjects. Wavelet decomposition was used to smooth and dissect the respiratory-related evoked potentials in frequency and time in 8 frequency bands. After denoising, selected wavelet scales were used to reconstruct the respiratory-related evoked potentials, which were quantified by using global field power estimates. The time course of the global field power activity in OSAS subjects compared with normal subjects was significantly depressed in the period 55-70 ms poststimulus onset, a time when afferent traffic from upper airway receptors arrives in normal subjects. The reduced evoked response in subjects with OSAS suggests that these subjects receive less afferent input from upper airway mechanoreceptors. This may reflect reduced sensitivity of mechanoreceptors or reduced mechanoreceptor stimulation due to decreased upper airway compliance during wakefulness in OSAS.     

Midlatency respiratory-related somatosensory activity and perception of oral pressure pulses in normal humans.

A direct relationship exists within subjects between midlatency features (<100 ms poststimulus) of respiratory-related evoked potentials and the perceived magnitude of applied oral pressure pulse stimuli. We evaluated perception in 18 normal subjects using cross-modality matching of applied pressure pulses via grip force and estimated mechanoafferent activity in these subjects by computing the global field power (GFP) from respiratory-related evoked potentials recorded over the right side of the scalp. We compared across subjects 1) the predicted magnitude production for a standard pressure pulse and 2) the slope (beta) and 3) the intercept (INT) of the Stevens power law to the summed GFP over 20-100 ms poststimulus. Both the magnitude production for a standard pressure pulse and the beta showed an inverse relationship with the summed GFP over 20-100 ms poststimulus, although there was no relationship between INT and the summed GFP. This may partially reflect characteristics of the mechanosensors and surely includes aspects of cognitive judgment, because we found and corrected for a high correlation between, respectively, beta (and INT) for pressure pulses and beta (and INT) for estimation of line lengths, a nonrespiratory modality. The relatively shallow, even inverse GFP-to-perception relationship suggests that, despite marked differences in the magnitude of afferent traffic, normal subjects seem to perceive things similarly.     

Decrease in lung volume-related feedback enhances laryngeal reflexes to negative pressure.

Negative pressure applied to the upper airway has an excitatory effect on the activity of upper airway muscles and an inhibitory effect on thoracic inspiratory muscles. The role of lung volume feedback in this response was investigated in 10 anesthetized spontaneously breathing adult rabbits. To alter lung volume feedback, the lower airway was exposed to SO2 (250 ppm for 15 min), thereby blocking slowly adapting receptors (SARs). Negative pressure pulses (5, 10, and 20 cmH2O, 300-ms duration) were applied to the functionally isolated upper airway before and after SAR blockade. Tracheal airflow and electromyogram (EMG) of the genioglossus and alae nasi were recorded. Peak EMG, peak inspiratory flow, tidal volume, and respiratory timing of control breaths (3 breaths immediately preceding test) and test breaths were determined. Analysis of variance was used to determine the significance of the effects. Negative pressure pulses increased peak EMG of genioglossus and alae nasi and inspiratory duration and decreased peak inspiratory flow. These effects were larger after SAR blockade. We conclude that a decrease in volume feedback from the lung augments the response to upper airway pressure change.     

Time of application of negative pressure pulses and upper airway muscle activity

Effect of upper airway pressure changes on thoracic inspiratory muscles has been shown to depend on the time of application during the breathing cycle. The present study was designed to investigate the importance of the time of application of upper airway negative pressure pulses on upper airway muscles. The upper airway was functionally isolated into a closed system in 24 anesthetized spontaneously breathing rabbits. Negative pressure pulses were applied in early (within the first 200 ms) and late (greater than or equal to 200 ms) inspiration, while electromyograms (EMG) of the diaphragm (Dia), genioglossus (GG), alae nasi (AN), and/or posterior cricoarytenoid (PCA) muscles were simultaneously monitored. When negative pressure pulse was applied in early inspiration, the increase in GG activity was greater [0.49 +/- 0.37 to 4.24 +/- 3.71 arbitrary units (AU)] than when negative pressure was applied in late inspiration (0.44 +/- 0.29 to 2.64 +/- 3.05 AU). Similarly, increased activation of AN (2.63 +/- 1.01 to 4.26 +/- 1.69 AU) and PCA (3.46 +/- 1.16 to 6.18 +/- 2.93 AU) was also observed with early inspiratory application of negative pressure pulses; minimal effects were seen in these muscles with late application. An inhibitory effect on respiratory timing consisting of a prolongation in inspiration (TI) and a decrease in peak Dia EMG/TI was observed as previously reported. These results indicate that the time of application of negative pressure during the breathing cycle is an important variable in determining the magnitude of the response of upper airway muscles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Low temperature painful stimulus alters brain wave pattern of transcutaneous electrical stimulus

The somatosensory evoked response recorded from the scalp over the somatosensory cortex was used to examine the interaction between painful cold and transcutaneous electrical stimuli delivered concomitantly. When a painful cold stimulus was applied to the palmar receptive field of the median nerve while that nerve was being stimulated with electrical pulses at the wrist, there was an augmentation of an early component of the somatosensory evoked response manifested by an increase in the amplitude of a wave segment in comparison with room temperature controls. This augmentation depended on there being normal conduction of nerve impulses in both the population of small and large peripheral nerve fibers as compared to a state in which conduction was blocked selectively by a local anesthetic or a pressure cuff in those small and large fibers, respectively. The augmentation was not found to be characteristic of an arousal phenomenon, but was localized to the somatosensory cortex. This might represent the effects of a non-specific thalamortical projection system on a specific one.     

Imaging the spatio-temporal dynamics of supragranular activity in the rat somatosensory cortex in response to stimulation of the paws

We employed voltage-sensitive dye (VSD) imaging to investigate the spatio-temporal dynamics of the responses of the supragranular somatosensory cortex to stimulation of the four paws in urethane-anesthetized rats. We obtained the following main results. (1) Stimulation of the contralateral forepaw evoked VSD responses with greater amplitude and smaller latency than stimulation of the contralateral hindpaw, and ipsilateral VSD responses had a lower amplitude and greater latency than contralateral responses. (2) While the contralateral stimulation initially activated only one focus, the ipsilateral stimulation initially activated two foci: one focus was typically medial to the focus activated by contralateral stimulation and was stereotaxically localized in the motor cortex; the other focus was typically posterior to the focus activated by contralateral stimulation and was stereotaxically localized in the somatosensory cortex. (3) Forepaw and hindpaw somatosensory stimuli activated large areas of the sensorimotor cortex, well beyond the forepaw and hindpaw somatosensory areas of classical somatotopic maps, and forepaw stimuli activated larger cortical areas with greater activation velocity than hindpaw stimuli. (4) Stimulation of the forepaw and hindpaw evoked different cortical activation dynamics: forepaw responses displayed a clear medial directionality, whereas hindpaw responses were much more uniform in all directions. In conclusion, this work offers a complete spatio-temporal map of the supragranular VSD cortical activation in response to stimulation of the paws, showing important somatotopic differences between contralateral and ipsilateral maps as well as differences in the spatio-temporal activation dynamics in response to forepaw and hindpaw stimuli.     

Effect of TPMPA (GABAC receptor antagonist) on neuronal response properties in rat barrel cortex

GABA_C receptors are ligand-gated chloride channels and have important roles in some neurological functions like vision. Recent investigations demonstrated that these receptors are also expressed in the somatosensory cortex. In this study, we investigated the effect of (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) (GABA_C receptor antagonist) on the properties of the neuronal response to natural stimuli (whisker deflection) in deep layers of rat barrel cortex. Twenty-eight male Wistar rats, weighing 230–260?g, were used in this study. TPMPA (100?μmol/rat) was administered intracerebroventricularly (ICV). Neuronal responses to deflection of principal (PW) and adjacent (AW) whiskers were recorded in barrel cortex using tungsten microelectrodes. A computer-controlled mechanical displacement was used to deflect whiskers individually or in combination at 30?ms inter-stimulus intervals. ON and OFF responses for PW and AW deflections were measured. A condition-test ratio (CTR) was computed to quantify neuronal responses to whisker interactions. Our data suggest that ICV administration of TPMPA increased neuronal spontaneous activity, ON and OFF responses to PW, and/or AW deflections. However, CTR for neither ON nor OFF responses changed following TPMPA administration. The results of this study demonstrated that inhibition of GABA_C receptors by TPMPA can modulate neuronal response properties in rat barrel cortex.     

Influence of body position on cortical pain-related somatosensory processing: an ERP study

Background

Despite the consistent information available on the physiological changes induced by head down bed rest, a condition which simulates space microgravity, our knowledge on the possible perceptual-cortical alterations is still poor. The present study investigated the effects of 2-h head-down bed rest on subjective and cortical responses elicited by electrical, pain-related somatosensory stimulation.

Methodology/Principal Findings

Twenty male subjects were randomly assigned to two groups, head-down bed rest (BR) or sitting control condition. Starting from individual electrical thresholds, Somatosensory Evoked Potentials were elicited by electrical stimuli administered randomly to the left wrist and divided into four conditions: control painless condition, electrical pain threshold, 30% above pain threshold, 30% below pain threshold. Subjective pain ratings collected during the EEG session showed significantly reduced pain perception in BR compared to Control group. Statistical analysis on four electrode clusters and sLORETA source analysis revealed, in sitting controls, a P1 component (40–50 ms) in the right somatosensory cortex, whereas it was bilateral and differently located in BR group. Controls'' N1 (80–90 ms) had widespread right hemisphere activation, involving also anterior cingulate, whereas BR group showed primary somatosensory cortex activation. The P2 (190–220 ms) was larger in left-central locations of Controls compared with BR group.

Conclusions/Significance

Head-down bed rest was associated to an overall decrease of pain sensitivity and an altered pain network also outside the primary somatosensory cortex. Results have implications not only for astronauts'' health and spaceflight risks, but also for the clinical aspects of pain detection in bedridden patients at risk of fatal undetected complications.     

Spike-timing-dependent BDNF secretion and synaptic plasticity

In acute hippocampal slices, we found that the presence of extracellular brain-derived neurotrophic factor (BDNF) is essential for the induction of spike-timing-dependent long-term potentiation (tLTP). To determine whether BDNF could be secreted from postsynaptic dendrites in a spike-timing-dependent manner, we used a reduced system of dissociated hippocampal neurons in culture. Repetitive pairing of iontophoretically applied glutamate pulses at the dendrite with neuronal spikes could induce persistent alterations of glutamate-induced responses at the same dendritic site in a manner that mimics spike-timing-dependent plasticity (STDP)—the glutamate-induced responses were potentiated and depressed when the glutamate pulses were applied 20 ms before and after neuronal spiking, respectively. By monitoring changes in the green fluorescent protein (GFP) fluorescence at the dendrite of hippocampal neurons expressing GFP-tagged BDNF, we found that pairing of iontophoretic glutamate pulses with neuronal spiking resulted in BDNF secretion from the dendrite at the iontophoretic site only when the glutamate pulses were applied within a time window of approximately 40 ms prior to neuronal spiking, consistent with the timing requirement of synaptic potentiation via STDP. Thus, BDNF is required for tLTP and BDNF secretion could be triggered in a spike-timing-dependent manner from the postsynaptic dendrite.     

Differential effects of painful and non-painful stimulation on tactile processing in fibromyalgia syndrome and subjects with masochistic behaviour

Background

In healthy subjects repeated tactile stimulation in a conditioning test stimulation paradigm yields attenuation of primary (S1) and secondary (S2) somatosensory cortical activation, whereas a preceding painful stimulus results in facilitation.

Methodology/Principal Findings

Since previous data suggest that cognitive processes might affect somatosensory processing in S1, the present study aims at investigating to what extent cortical reactivity is altered by the subjective estimation of pain. To this end, the effect of painful and tactile stimulation on processing of subsequently applied tactile stimuli was investigated in patients with fibromyalgia syndrome (FMS) and in subjects with masochistic behaviour (MB) by means of a 122-channel whole-head magnetoencephalography (MEG) system. Ten patients fulfilling the criteria for the diagnosis of FMS, 10 subjects with MB and 20 control subjects matched with respect to age, gender and handedness participated in the present study. Tactile or brief painful cutaneous laser stimuli were applied as conditioning stimulus (CS) followed by a tactile test stimulus (TS) 500 ms later. While in FMS patients significant attenuation following conditioning tactile stimulation was evident, no facilitation following painful stimulation was found. By contrast, in subjects with MB no attenuation but significant facilitation occurred. Attenuation as well as facilitation applied to cortical responses occurring at about 70 ms but not to early S1 or S2 responses. Additionally, in FMS patients the amount of attenuation was inversely correlated with catastrophizing tendency.

Conclusion

The present results imply altered cortical reactivity of the primary somatosensory cortex in FMS patients and MB possibly reflecting differences of individual pain experience.     

The neural basis of tactile texture perception

Running our fingers across a textured surface gives rise to two types of skin deformations, each transduced by different tactile nerve fibers. Coarse features produce large-scale skin deformations whose spatial configuration is reflected in the spatial pattern of activation of some tactile fibers. Scanning a finely textured surface elicits vibrations in the skin, which in turn evoked temporally patterned responses in other fibers. These two neural codes—spatial and temporal—drive a spectrum of neural response properties in somatosensory cortex: At one extreme, neurons are sensitive to spatial patterns and encode coarse features; at the other extreme, neurons are sensitive to vibrations and encode fine features. While the texture responses of nerve fibers are dependent on scanning speed, those of cortical neurons are less so, giving rise to a speed invariant texture percept. Neurons in high-level somatosensory cortices combine information about texture with information about task variables.     

Bat Avoidance in Non-Aerial Insects: The Silence Response of Signaling Males in an Acoustic Moth

While the evasive responses of many flying acoustic insects to aerial‐hawking bats are duly recognized and studied, the responses of non‐aerial insects to gleaning bats are generally overlooked. It has been assumed that acoustic insects are deaf to these predators because gleaning bat echolocation calls are typically low in amplitude, brief (1–3 ms) and very high in frequency (>60 kHz). We tested this assumption in a series of playback experiments with a moth (Achroia grisella) that uses hearing in both predator evasion and mating. We report that ultrasound pulses ≥78 dB peSPL (peak equivalent sound pressure level) and ≥1 ms in duration inhibit stationary males from broadcasting their own ultrasonic advertisement calls, provided that the pulsed stimuli are delivered at a repetition rate ≤30/s. Further analyses suggest that inhibition by pulsed ultrasound comprises two processes performed serially. First, a startle response with a latency <50 ms is elicited by a single pulse ≥1 ms duration. Here, a male misses broadcasting several calls over a 50–100 ms interval. Secondly, the startle may be extended as a silence response lasting several to many seconds if subsequent pulses occur at a rate ≤30/s. Call inhibition cannot represent a simple response to acoustic power because of the inverse interaction between pulse duration and rate. On the other hand, the temporal and energy characteristics of inhibitory stimuli match those of gleaning bat echolocation calls, and we infer that inhibition is a specialized defensive behavior by which calling males may avoid detection by eavesdropping bats.     

Differences in kinetics between GABAC and GABAA receptors on carp retinal bipolar cells

The present work was undertaken to characterize kinetics, including activation, desensitization and deactivation, of responses mediated by GABAA and GABAC receptors on carp retinal bipolar cells, using the whole-cell patch-clamp technique. It was revealed that the GABAC response was generally slower in kinetics than the GABAA response. Activation kinetics of both the receptors could be well fit by monoexponential functions with time constants τ, being 44.57 ms (GABAC) and 10.86 ms (GABAA) respectively. Desensitization of the GABAA response was characterized by a fast and a slow exponential component with time constants of τfast = 2.16 s and τslow = 19.78 s respectively, whereas desensitization of the GABAC response was fit by a monoexponential function of the time constant τ = 6.98 s. Deactivation at both the receptors was adequately described by biexponential functions with time constants being much higher for the GABAC response (τfast = 674.8 ms; τslow = 2 090 ms) than those for the GABAA response (τfast = 42.07 ms; τslow = 275.1 ms). These differences in kinetics suggest that GABAC and GABAA receptors may be involved in processing signals in different frequency domains.     

Interhemispheric interactions between the human primary somatosensory cortices

In the somatosensory domain it is still unclear at which processing stage information reaches the opposite hemispheres. Due to dense transcallosal connections, the secondary somatosensory cortex (S2) has been proposed to be the key candidate for interhemispheric information transfer. However, recent animal studies showed that the primary somatosensory cortex (S1) might as well account for interhemispheric information transfer. Using paired median nerve somatosensory evoked potential recordings in humans we tested the hypothesis that interhemispheric inhibitory interactions in the somatosensory system occur already in an early cortical processing stage such as S1. Conditioning right S1 by electrical median nerve (MN) stimulation of the left MN (CS) resulted in a significant reduction of the N20 response in the target (left) S1 relative to a test stimulus (TS) to the right MN alone when the interstimulus interval between CS and TS was between 20 and 25 ms. No such changes were observed for later cortical components such as the N20/P25, N30, P40 and N60 amplitude. Additionally, the subcortically generated P14 response in left S1 was also not affected. These results document the existence of interhemispheric inhibitory interactions between S1 in human subjects in the critical time interval of 20-25 ms after median nerve stimulation.     

Cross-trial correlation analysis of evoked potentials reveals arousal-related attenuation of thalamo-cortical coupling

We describe a computational method for assessing functional connectivity in sensory neuronal networks. The method, which we term cross-trial correlation, can be applied to signals representing local field potentials (LFPs) evoked by sensory stimulations and utilizes their trial-to-trial variability. A set of single trial samples of a given post-stimulus latency from consecutive evoked potentials (EPs) recorded at a given site is correlated with such sets for all other latencies and recording sites. The results of this computation reveal how neuronal activities at various sites and latencies correspond to activation of other sites at other latencies. The method was used to investigate the functional connectivity of thalamo-cortical network of somatosensory system in behaving rats at two levels of alertness: habituated and aroused. We analyzed potentials evoked by vibrissal deflections recorded simultaneously from the ventrobasal thalamus and barrel cortex. The cross-trial correlation analysis applied to the early post-stimulus period (<25 ms) showed that the magnitude of the population spike recorded in the thalamus at 5 ms post-stimulus correlated with the cortical activation at 6–13 ms post-stimulus. This correlation value was reduced at 6–9 ms, i.e. at early postsynaptic cortical response, with increased level of the animals’ arousal. Similarly, the aroused state diminished positive thalamo-cortical correlation for subsequent early EP waves, whereas the efficacy of an indirect cortico-fugal inhibition (over 15 ms) did not change significantly. Thus we were able to characterize the state related changes of functional connections within the thalamo-cortical network of behaving animals.     

Waking and genioglossus muscle responses to upper airway pressure oscillation in sleeping dogs

We studied waking and genioglossus electromyographic (EMGgg) responses to oscillating pressure waves applied to the upper airways of three sleeping dogs. The dogs were previously prepared with a permanent side-hole tracheal stoma and were trained to sleep with a tight-fitting snout mask, hermetically sealed in place, while breathing through a cuffed endotracheal tube inserted through the tracheostomy. Sleep state was determined by behavioral, electroencephalographic, and electromyographic criteria, and EMGgg activity was measured using fine bipolar electrodes inserted directly into the muscle. Oscillatory pressure waves of 30 Hz and +/- 3 cmH2O (tested at atmospheric and subatmospheric upper airway pressures) were applied at the dog's nostrils or larynx, either constantly for a period of 1 min or in 0.5-s bursts. We found that the pressure stimulus had two major effects. First, it was a potentially powerful arousal-promoting stimulus. Arousal occurred in 78% of tests in slow-wave sleep (SWS) and 55% of tests in rapid-eye-movement (REM) sleep, with swallowing and sighing accompanying many of the arousals. Second, it produced an immediate and sustained augmentation of EMGgg, in wakefulness, SWS, and REM sleep. We conclude that oscillatory pressure waves in the upper airway, as found in snoring, produce reflex responses that help maintain upper airway patency during sleep. Loss of this type of reflex might contribute to the onset of obstructive sleep apnea in chronic snorers.     

Use of the laryngeal mask airway in rabbits: placement and efficacy

The laryngeal mask airway (LMA) has been used in various animal species anesthetized for the purpose of device evaluation, but the device has not been evaluated in rabbits during surgery. The authors tested the feasibility and potential advantages of using the LMA in 50 rabbits undergoing surgery under spontaneous-breathing inhalational anesthesia, focusing mainly on the technique of insertion and its efficacy. The LMA was easily inserted and no air leakage at the larynx was detected. Although four rabbits developed lingual cyanosis, this was reversible and most likely due to lingual vascular compression by the LMA. The authors conclude that the LMA is an attractive alternative to endotracheal intubation, as the mask can be inserted easily and rapidly and its correct placement is easily confirmed.     

Effects of upper airway pressure on abdominal muscle activity in conscious dogs.

We have examined arousal and abdominal muscle electromyogram (EMGabd) responses to upper airway pressure stimuli during physiological sleep in four dogs with permanent side-hole tracheal stomata. The dogs were trained to sleep with a tightly fitting snout mask, hermetically sealed in place, while breathing through a cuffed endotracheal tube inserted through the tracheostomy. Sleep stage was determined by behavioral and electroencephalographic criteria. EMGabd activity was measured using bipolar fine-wire electrodes inserted into the abdominal muscle layers. Static increases or decreases in upper airway pressure (+/- 6 cmH2O), when applied at the snout mask or larynx (upper trachea), caused an immediate decrease in EMGabd on the first two to three breaths; EMGabd usually returned to control levels within the 1-min test interval. In contrast, oscillatory pressure waves at 30 Hz and +/- 3 cmH2O amplitude (or -2 to -8 cmH2O amplitude) produced an immediate and sustained reduction in IMGabd in all sleep states. Inhibition of EMGabd could be maintained over many minutes when the oscillatory pressure stimulus was pulsed by using a cycle of 0.5 s on and 0.5 s off. Oscillatory upper airway pressures were also found to be powerful arousal-promoting stimuli, producing arousal in 94% of tests in drowsiness and 66% of tests in slowwave sleep. The results demonstrate the presence of breath-by-breath upper airway control of abdominal muscle activity.