Respiratory-related Evoked Potentials Components Research Articles

Brain Activations to Dyspnea in Patients With COPD.

We compared the perception and neural processing of respiratory sensations between 20 COPD patients and 20 healthy controls by means of respiratory-related evoked potentials (RREP) in the electroencephalogram (EEG). RREPs were induced by short inspiratory occlusions while 129-channel EEG was measured. COPD patients rated the occlusions as more intense and unpleasant (p’s < 0.001) and showed higher mean amplitudes for the RREP components P1 (p = 0.0004), N1 (p = 0.024), P2 (p = 0.019), and P3 (p = 0.018). Our results indicate that COPD patients demonstrate greater perception and neural processing of respiratory sensations, which presumably reflects the highly aversive and attention-demanding character of these sensations for COPD patients.

Supra-threshold inspiratory loads elicit respiratory related evoked potentials in healthy subjects

Objectives Respiratory-related evoked potential (RREP) are well-established cerebral correlates of respiratory perceptions. The early components N1/P1 reflect first-order sensory processing of afferent respiratory signals in brain sensorimotor regions while the late ones P2/P3 involve higher-order cognitive processing [1] . The current stimuli used to elicited RREP are short occlusions at the onset of an inspiration or a transiant interruption of the inspiration [1] . Durations of the inspiratory occlusion do not affect RREP components [3] while there is a linear relationship between inspiratory loads and RREP components amplitudes. Moreover, an inspiration load needs to reach some threshold value to elicit RREP [1] , [2] . Here, we investigated whether supra-threshold load inspiration could induce RREP without occlusion. Methods EEG was synchronously recorded with the respiratory signals in 11 healthy volunteers breathing into a mouthpiece connected to a non-rebreathing valve. Four consecutives inspiration loads were produced by a pressure-threshold device connected to the non-rebreathing valve: no_Load, 10, 20 and 30 cmH2O/L/sec. Each load was presented during 5 minutes and there is a 3-min resting time between two consecutives loads presentations. Magnitude estimation (ME) for each load was scored with the A1 subscale of the Multi-dimensional profile of dyspnea. Inspiration onset time locked EEG epochs were averaged for each breathing conditions and examined for presence of RREP components. Results The no_load condition did not elicit any peak of RREP, but 10, 20 and 30 cmH2O/L/sec produced N1 and P3 RREP components with amplitudes correlating with the loads as well as the loads’ magnitude estimation. Mean amplitudes of the N1 and P3 RREP components for 10, 20 and 30 cmH2O/L/sec were respectively 3.6 ± 0.5, 5.6 ± 0.9, 3.8 ± 1.3 and −4.5 ± 1.3, −11.4 ± 2.4, −7.6 ± 2.2 μV. Conclusion Supra-threshold load inspiration could induce RREP without occlusion. This method should be compared with the standard inspiration occlusion method.

Emotions and Neural Processing of Respiratory Sensations Investigated With Respiratory-Related Evoked Potentials

Patients with respiratory diseases such as asthma and chronic obstructive pulmonary disease frequently experience respiratory sensations, which are often perceived as unpleasant or threatening. However, the accurate perception of respiratory sensations is important for the management and treatment of these diseases. Emotions can substantially influence the perception of respiratory sensations and might affect the course of respiratory diseases, but the underlying neural mechanisms are poorly understood. The respiratory-related evoked potential (RREP) recorded from the electroencephalogram is a noninvasive technique that allowed first studies to examine the impact of emotions on the neural processing of respiratory sensations. In this review, we will briefly introduce the importance of the perception of respiratory sensations and the influence of emotions on respiratory perception. We then provide an overview on the technique of RREP and present a systematic review on recent findings using this technique in the context of emotions. The evidence currently available from studies in healthy individuals suggests that short-lasting emotional states and anxiety affect the later RREP components (N1, P2, P3) related to higher-order neural processing of respiratory sensations, but not the earlier RREP components (Nf, P1) related to first-order sensory processing. We conclude with a discussion of the implications of this work for future research that needs to focus on respiratory patient groups and the associated clinical outcomes.

The impact of anxiety on the neural processing of respiratory sensations

Previous studies demonstrated that anxiety considerably impacts the reported perceptions of respiratory sensations. A novel feature of the current study is exploring the impact of anxiety on the neural processing of respiratory sensations elicited by short inspiratory occlusions during different affective contexts. Using high-density EEG, respiratory-related evoked potentials (RREP) were recorded in 23 low and 23 matched higher anxious individuals when viewing unpleasant or neutral picture series. Low anxious individuals showed the expected pattern of reduced magnitudes of later RREP components P2 and P3 during the unpleasant compared to the neutral affective context (p<0.05 and p<0.01). In contrast, higher anxious individuals showed greater magnitudes of P2 and P3 during the unpleasant compared to the neutral affective context (p's<0.05). Moreover, higher anxiety levels were correlated with greater magnitudes for P2 (r=0.44, p<0.01) and P3 (r=0.54, p<0.001) during the unpleasant relative to the neutral affective context. Earlier components of the RREP (Nf, P1, N1) were not affected by anxiety. This study demonstrates that anxiety affects the later, higher-order neural processing of respiratory sensations, but not its earlier, first-order sensory processing. These findings might represent a neural mechanism that underlies the increased perception of respiratory sensations in anxious individuals.

Respiratory-related evoked potential measurements using high-density electroencephalography

Objective The respiratory-related evoked potential (RREP) has become an established technique for studying the neural processing of respiratory signals. However, the increasing availability of high-density EEG systems necessitates new criteria for obtaining acceptable RREPs with these systems. Methods The present study examined the minimum criteria for the number of inspiratory occlusions that need to be averaged in order to obtain a signal-to-noise ratio of 2:1 (3 dB) for the RREP components Nf, P1, N1, P2 and P3 with a 129 sensor high-density EEG system in 12 healthy volunteers. RREPs resulting from averaging 8, 16, 32 and 64 inspiratory occlusions were compared. Results Analyses of signal-to-noise ratios demonstrated that a minimum of 32 and 16 inspiratory occlusions should be averaged for Nf and P1, respectively. For N1, P2, and P3, an average of at least 8 inspiratory occlusions is required. However, to account for inter-individual variability, 64 averaged occlusions for Nf, 32 averaged occlusions for P1, and 16 averaged occlusions for N1, P2, and P3 are recommended which more reliably exceed the signal-to-noise threshold. Conclusions These numbers provide the minimum and the recommended criteria for reliable measurements of the RREP for an adequate number of repeated occlusion epochs to be averaged in order to yield a reliable signal-to-noise ratio using a 129 sensor EEG system. Significance The present study provides minimum and recommended criteria for obtaining acceptable RREPs with high-density EEG systems.

Habituation in neural processing and subjective perception of respiratory sensations

Reduced perception of respiratory sensations is associated with negative treatment outcome in asthma. We examined whether habituation in the neural processing of repeatedly experienced respiratory sensations may underlie subjective reports of reduced respiratory perception. Respiratory-related evoked potentials (RREP) elicited by inspiratory occlusions and reports of respiratory perception were compared between early and late experimental periods in healthy subjects. Reports of respiratory perception were reduced during late, compared to early, experimental periods. This was paralleled by reduced magnitudes in RREP components N1, P2, and P3 in late, compared to early, experimental periods. Habituation in the neural processing of respiratory sensations is a potential mechanism that underlies subjective reports of reduced respiratory perception and might represent a risk factor for reduced perception of respiratory sensations in asthma.

The impact of emotion on respiratory-related evoked potentials

Emotion influences the perception of respiratory sensations, although the specific mechanism underlying this modulation is not yet clear. We examined the impact of viewing pleasant, neutral, and unpleasant affective pictures on the respiratory-related evoked potential (RREP) elicited by a short inspiratory occlusion in healthy volunteers. Reduced P3 amplitude of the RREP was found for respiratory probes presented when viewing pleasant or unpleasant series, when compared to those presented during the neutral series. Earlier RREP components, such as Nf, P1, N1, and P2, showed no modulation by emotion. The results suggest that emotion impacts the perception of respiratory sensations by reducing the attentional resources available for processing afferent respiratory sensory signals.

Neural Processing of Respiratory Sensations when Breathing Becomes More Difficult and Unpleasant

The accurate perception of respiratory sensations is important for the successful management and treatment of respiratory diseases. Previous studies demonstrated that external stimuli such as affective pictures and distracting films can impact the perception and neural processing of respiratory sensations. This study examined the neural processing of respiratory sensations when breathing as an internal stimulus is manipulated and becomes more difficult and unpleasant. Sustained breathing through an inspiratory resistive load was used to increase perceived breathing difficulty in 12 female individuals without respiratory disease. Using high-density EEG, respiratory-related evoked potentials (RREP) to short inspiratory occlusions were recorded at early versus late time points of sustained loaded breathing. Ratings of perceived intensity and unpleasantness of breathing difficulty showed an increase from early to late time points of loaded breathing (p < 0.01 and p < 0.05, respectively). This was paralleled by significant increases in the magnitudes of RREP components N1, P2, and P3 (p < 0.01, p < 0.05, and p < 0.05, respectively). The present results demonstrate increases in the neural processing of respiratory sensations when breathing becomes more difficult and unpleasant. This might reflect a protective neural mechanism allowing effective response behavior when air supply is at risk.

Cortical sources of the respiratory-related evoked potential

The respiratory-related evoked potential (RREP) is increasingly used to study the neural processing of respiratory signals. However, little is known about the cortical origins of early (Nf, P1, N1) and later RREP components (P2, P3). By using high-density EEG, we studied cortical sources of RREP components elicited by short inspiratory occlusions in 18 healthy volunteers (6 female, mean age 20.0+/-1.8 years). Topographical maps for Nf and P1 showed bilateral maximum EEG voltages over the frontal and centro-parietal cortex, respectively. Cortical source analyses (minimum-norm estimates) in addition to topographical maps demonstrated bilateral sensorimotor cortex origins for N1 and P2 which were paralleled by an additional frontal cortex source (p's<0.05). The source of the P3 was located at the parietal cortex (p<0.05). The results support previous findings on the cortical sources of early RREP components Nf, P1 and N1 and demonstrate the cortical sources of later RREP components P2 and P3.

Cortical processing of respiratory afferent stimuli during sleep in children with the obstructive sleep apnea syndrome.

Children with the obstructive sleep apnea syndrome (OSAS) have blunted upper airway responses to negative pressure, but the underlying cause remains unknown. Cortical processing of respiratory afferent information can be tested by measuring respiratory-related evoked potentials (RREPs). We hypothesized that children with OSAS have blunted RREP responses compared to normal children during sleep. During sleep, RREPs were obtained from EEG electrodes Fz, Cz, Pz during stage 2 sleep, slow wave sleep (SWS), and REM sleep. RREPs were produced with multiple short occlusions of the upper airway. Sleep laboratory. 9 children with OSAS and 12 normal controls. Children with OSAS had significantly decreased evoked K-complex production in stage 2 sleep and slow wave sleep and significantly reduced RREP N350 and P900 components in slow wave sleep. There were no significant differences in any of the measured RREP components in stage 2 sleep, and the only REM difference was decreased P2 amplitude. Results indicate that in children with OSAS, cortical processing of respiratory-related information measured with RREPs persists throughout sleep; however, RREPs during SWS are blunted compared to those seen in control children. Possible causes for this difference include a congenital deficit in neural processing reflective of a predisposition to develop OSAS, or changes in the upper airway rendering the airway less capable of transducing pressure changes following occlusion. Further research is required to evaluate RREPs after effective surgical treatment of OSAS in children, in order to distinguish between these alternatives.

Respiratory-Related Evoked Potentials During Sleep in Children

The respiratory related evoked potential (RREP) has been previously recorded in children and adults during wakefulness and in adults during sleep. However, there have been no data on RREP during sleep in children. We thus examined children during sleep to determine whether early RREP components would be maintained during all sleep Twelve healthy, nonsnoring children, aged 5-12 years, screened by polysomnography and found to have no sleep disorders were assessed during stage 2 sleep, slow wave sleep, and REM sleep. Brief occlusions were presented via an occlusion valve at the inspiratory port of a non-rebreathing valve as interruptions of inspiration. EEG responses were averaged and assessed for the presence of early and late RREP components. Robust early components were seen in the majority of subjects in all sleep stages. Late components were also present, although with some apparent differences compared to those previously reported in adults (using the same recording protocol and an almost identical method of stimulus presentation). Specifically, N350 and N550 were less readily differentiated as separate components, and the N550 did not display the clear anterior-posterior amplitude gradient that is ubiquitous in adults. Cortical processing of respiratory-related information persists throughout sleep in children. The pattern of activation in the late components appear to reflect differences in the structure of the developing brain prior to the process of dendritic pruning associated with adolescence.

Respiratory-related evoked potentials in children with asthma

Aims of the study Respiratory-related evoked potentials (RREPs) are a method of recording brain activities in response to respiratory stimuli. Although data in childhood are scarce, the absence of the early P1 component of RREPs has been reported in children with a history of life-threatening asthma. This study was focused on the presence, latencies, and amplitudes of the P1, N1, P2, and N2 components of the RREPs in a paediatric series of asthmatic patients. Patients and methods RREPs were recorded in 21 patients with stable asthma, age range 8–17 years, 11 healthy children, age range 6–16 years, and 24 healthy adults, age range 20–28 years. The signals from left (C3–Cz) and right (C4–Cz) central (rolandic) location were recorded separately, using surface electrodes. Evoked responses to two series of 80 consecutive mid-inspiratory occlusions were averaged. Recordings were analysed manually. Results All 4 RREPs components were significantly more often absent in asthmatic children than in healthy children and adults (P1, p = 0.01; N1, p = 0.008; P2, p = 0.008, N2, p = 0.01). The latencies and amplitudes of the four components were similar in patients and healthy subjects. Conclusion RREPs components were less frequently present in children with asthma than in healthy subjects. This finding should promote the recording of RREPs in other acute and chronic respiratory diseases in children in order to search for possible electroclinical correlations.

Detection threshold for inspiratory resistive loads and respiratory-related evoked potentials

The relationship between detection threshold of inspiratory resistive loads and the peaks of the respiratory-related evoked potential (RREP) is unknown. It was hypothesized that the short-latency and long-latency peaks of the RREP would only be elicited by inspiratory loads that exceeded the detection threshold. The detection threshold for inspiratory resistive loads was measured in healthy subjects with inspiratory-interruption or onset load presentations. In a separate protocol, the RREPs were recorded with resistive loads that spanned the detection threshold. The loads were presented in stimulus attend and ignore sessions. Onset and interruption load presentations had the same resistive load detection threshold. The P(1), N(f), and N(1) peaks of the RREP were observed with loads that exceeded the detection threshold in both attend and ignore conditions. The P(300) was present with loads that exceeded the detection threshold only in the attend condition. No RREP components were elicited with subthreshold loads. The P(1), N(f), and P(300) amplitudes varied with resistive load magnitude. The results support the hypothesis that there is a resistive load threshold for eliciting the RREPs. The amplitude of the RREP peaks vary as a function of load magnitude. The cognitive P(300) RREP peak is present only for detectable loads and when the subject attends to the stimulus. The absence of the RREP with loads below the detection threshold and the presence of the RREP elicited by suprathreshold loads are consistent with the gating of these neural measures of respiratory mechanosensory information processing.

Respiratory-related evoked potentials elicited by inspiratory occlusions in double-lung transplant recipients.

This study investigated the role of lung vagal afferents in the respiratory-related evoked potential (RREP) response to inspiratory occlusions by using double-lung transplant recipients as a lung denervation model. Evoked potential recordings in response to inspiratory occlusions were obtained from 10 double-lung transplant (DLT) recipients with normal lung function and 12 healthy control (Nor) subjects under the attend, ignore, and unoccluded conditions. Results demonstrated that early-latency RREP components (P(1), P(1a), N(f), and N(1)) were not significantly different between the DLT and the Nor groups. The late-latency RREP component (P(3)) was identifiable in all DLT subjects during the attend trial. However, P(3) latency was significantly longer in the DLT group compared with the Nor group. The zero-to-peak amplitude of P(3) was also significantly smaller in the DLT group than that in the Nor group during the attend trial. These results suggest that lung vagal afferents were not essential to elicit RREP responses, but may contribute to the cognitive processing of respiratory stimuli.

The respiratory‐related evoked potential: Effects of attention and occlusion duration

The present study assessed the effects of occlusion duration and attention on components of the respiratory-related evoked potential (RREP). Twenty-nine channel evoked potential recordings were obtained from 12 young adults exposed to a pseudorandom sequence of 100-, 200-, 400-, and 800-ms inspiratory occlusions, under attend and ignore conditions. Results demonstrated that the duration of an inspiratory occlusion does not affect RREP components systematically, highlighting the importance of the onset of the occlusion in producing the cortical responses. Attention resulted in augmentation of the N1, P2, and P3 components but did not affect the early latency Nf and P1 components. P1, N1, and P3 occurred with shorter latencies in the attend condition. One subject with poor duration estimation ability displayed substantially delayed P3 latency. This result highlights the relationship between P3 and perception of respiratory somatosensory information.

Respiratory-related evoked potentials during the transition from alpha to theta EEG activity in stage 1 NREM sleep.

It has been argued previously that evoked potential components during Stage 1 sleep in response to both auditory and respiratory stimuli are intermediate between those of wakefulness and Stage 2 sleep. However, state fluctuations in the ECG between alpha and theta during Stage 1 sleep have been linked to changes in a number of respiratory functions including ventilation, upper airway resistance and chemical drive. It was therefore hypothesized that if respiratory related evoked potentials (RREP) were averaged separately for alpha and theta EEG periods during Stage 1 sleep, the alpha RREP would resemble wakefulness and the theta RREP would resemble Stage 2 sleep. RREPs were produced by 250 ms occlusions in 10 subjects. EEG was recorded from 29 scalp sites, referenced to linked ears, together with EOG and EMG. The N1 component was not specifically associated with alpha vs. theta activity, but appeared to be sensitive to any decrease in arousal level, suggesting that it was more related to attention than to changes in the EEG. The late N2 and P300 components were present during wake and Stage 1 alpha. However, in Stage 1 theta, different late components emerged (N300 and P450) that differed in latency, amplitude or topographical distribution from those seen in wakefulness. The P2 proved difficult to interpret, whereas the N550 did not appear until Stage 2 sleep, and as such, was not dependent on alpha/theta state. The results indicate that RREP components are differentially affected by the transition into sleep.

Multichannel EEG analysis of respiratory evoked-potential components during wakefulness and NREM sleep

Airway occlusion in awake humans produces a somatosensory evoked response called the respiratory-related evoked potential (RREP). In the present study, 29 channel evoked-potential recordings were obtained from seven men who were exposed to 250-ms inspiratory airway occlusions during wakefulness, stage 1, stage 2, and slow-wave sleep. The RREP recorded during wakefulness was similar to previous reports, with the unique observation of an additional short-latency positive peak with a mean latency of 25 ms. Short-latency RREP components were maintained in non-rapid-eye-movement (NREM) sleep. The clearly seen N1 vertex and late positive complex components during wakefulness were markedly attenuated during NREM sleep, and two large negative components (N300 and N550) dominated the sleep RREP. These findings indicate the maintenance of central nervous system monitoring of respiratory afferent information during NREM sleep, presumably to facilitate protective arousal responses to pathophysiological respiratory phenomena.

Source dipole analysis of the early components of the RREP.

Occlusion of the inspiratory airway produces a series of early RREP components. The predominant early positive and negative peaks are seen over the parietal and frontal scalp respectively and have been hypothesised to represent parallel activation of somatosensory and motor cortices in a manner similar to electrically produced SEP components. An alternative hypothesis is that both components are produced by somatosensory cortex, with the frontally maximal negativity reflecting the activity of a tangential dipole source. Respiratory-related evoked potentials (RREPs) elicited by brief occlusion of the inspiratory airway, were recorded using 29 scalp electrodes from six subjects. Early latency components were analysed using the Electromagnetic Source Estimation (EMSE) program for modelling equivalent electrical dipoles, in order to suggest likely generator sources. Two hypotheses were tested: first, that radial dipoles generated by both pre- (motor cortex) and post-centrally (somatosensory cortex) produce the early components; and second, that generator sources are limited to the somatosensory cortex, with activity recorded as frontally maximal reflecting volume conduction from tangential dipoles. Results were highly consistent between subjects and suggested that Nf-P1 was best accounted for by two post-central and two pre-central radial dipoles supporting the first hypothesis. Locations of generator sources are discussed in relation to anatomical correlates.

Scalp topography of the short-latency components of the respiratory-related evoked potential in children.

Respiratory-related evoked potentials (RREPs) have been elicited by inspiratory occlusion and recorded at electroencephalographic (EEG) sites overlying the somatosensory cortex in adults. The present study was the first to be conducted in normal children and was designed to identify the scalp distribution of the early RREP components. EEG responses to occlusion were recorded from CZ-C3, CZ-C4, and 17 sites referenced to the linked earlobes. The RREP was observed in all subjects in the CZ-C3 and CZ-C4 electrode pairs. The earlobe-referenced recordings revealed two RREP patterns. The P1 and N1 peaks were found in C3, C4, P3, P4, T3, and T4. The RREPs recorded from the F3, F4, F7, and F8 electrodes did not exhibit either the P1 or N1 peaks. A negative peak (NF) occurred approximately 13 ms after the P1 peak. The results show that the RREPs to inspiratory occlusions were present bilaterally but diminished greatly over midline sites. Furthermore, consistent with mechanically and electrically elicited somatosensory evoked potentials, the RREP displayed a polarity inversion over the central sulcus in the early component latency range.