Pei-Ying S. Chan

Respiratory-related evoked potential measures of respiratory sensory gating.

The purpose of this study was to demonstrate a neural respiratory gating system using a paired stimuli paradigm. The N1 peak of the respiratory-related evoked potential (RREP) represents early perceptual processing of respiratory sensory information. This is similar to the N100 peak shown with tactile sensation, where the second peak amplitude (S2) of the N100 peak from the somatosensory evoked potential (SEP) was smaller than the first peak amplitude (S1) when the stimuli were presented 500 ms apart. We hypothesized that paired inspiratory occlusions would result in a reduced amplitude of the S2 N1 RREP peak amplitude, indicating respiratory central neural gating. Twenty healthy subjects (10 men and 10 women; 25.8 +/- 6.5 yr old) completed the paired inspiratory occlusion (RREP) trial. Thirteen of the subjects also completed the paired mouth air puffs [mouth-evoked potential (MEP) trial], and the paired hand air puffs (SEP) trial. All paired presentations were separated by 500 ms. The N1 peak amplitudes of the RREP trial and the N100 peak amplitudes of the MEP and SEP trials for S1 and S2 and the S2/S1 ratios were determined. The S1 RREP N1 peak amplitude was significantly greater than S2, and the S2/S1 ratio was 0.43. The S1 MEP and SEP N100 peak amplitudes were significantly greater than S2, and the N100 ratio was 0.49 and 0.49, respectively. These results are consistent with central neural gating of respiratory afferent input. The RREP gating response is similar to somatosensory mechanoreceptor gating.

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 (ps<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.

Emotions and neural processing of respiratory sensations investigated with respiratory-related evoked potentials.

Objective 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. Methods 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. Results and Conclusions 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.

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 (ps<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.

Respiratory related evoked potential measures of cerebral cortical respiratory information processing.

Normal breathing is usually not sensed by the individual. Individuals become aware of their breathing at the cognitive level when breathing pattern is manipulated. Airway obstruction activates lung and muscle mechanoreceptors that project to the somatosensory cortex. Cortical neuronal activation in the somatosensory cortex by inspiratory occlusions can be measured by scalp surface electrodes in humans. The averaged signal was defined as the respiratory related evoked potential (RREP). Six RREP peaks, Nf, P1, N1, P2, N2 and P300 have been studied in the averaged EEG trace. Voluntary attention, background loads, and disease state were found to modulate the RREP. Respiratory sensory gating was demonstrated with the RREP using different levels of intensities and frequencies of respiratory stimuli. Future studies are needed to investigate the effects of psychological states, such as attention and emotion, as well as non-respiratory modalities, such as visual, auditory, and tactile sensations, on the RREP.

Respiratory-related-evoked potential measures of respiratory sensory gating in attend and ignore conditions.

Respiratory sensory gating is evidenced by decreased respiratory-related-evoked potentials (RREP) amplitude of the N1 peak for the second stimulus (S2) when two occlusions are separated by a 500-millisecond interval. The RREP N1 peak amplitude ratio of the S2 and the first occlusion (S1), S2/S1, is usually <0.5. Controlled attention of respiratory loads is measured by the P300 peak of the RREP. We hypothesized that the paired occlusion elicited N1 and the P300 peak amplitudes will be modulated by controlled attention. The RREP was recorded in ignore and attend trials. The amplitudes of the RREP Nf, P1, N1, and P300 peaks for S1 and S2 and the S2/S1 ratios were measured for both trials. The S1 amplitudes of the Nf, P1, and N1 peaks were not significantly different between the attend and ignore conditions. The S2 Nf, P1, and N1 peak amplitudes were not significantly different between conditions but were all significantly less than S1. The S2/S1 ratios for Nf, P1, and N1 peaks were not significantly different between the attend and ignore conditions. The S1 RREP P300 peak amplitude in attend trials was significantly greater than in ignore trails. The attend S1 P300 amplitude was significantly greater than the attend S2 amplitude. The attend P300 S2/S1 ratio was significantly less than the ignore ratio. These results demonstrated that respiratory gating is evident in both attend and ignore conditions. The P300 peak S2/S1 ratio is consistent with controlled attention modulation of central neural gating of respiratory mechanosensation.

The role of nicotine on respiratory sensory gating measured by respiratory-related evoked potentials.

Respiratory perception can be altered by changes in emotional or psychological states. This may be due to affective (i.e., anxiety) modulation of respiratory sensory gating. Nicotine withdrawal induces elevated anxiety and decreased somatosensory gating. Respiratory sensory gating is evidenced by decreased amplitude of the respiratory-related evoked potentials (RREP) N(1) peak for the second occlusion (S2) when two 150-ms occlusions are presented with a 500-ms interval during an inspiration. The N(1) peak amplitude ratio of the S2 and first occlusion (S1) (S2/S1) is <0.5 and due to central neural sensory gating. We hypothesized that withdrawal from nicotine is anxiogenic and reduces respiratory gating in smokers. The RREP was recorded in smokers with 12-h withdrawal from nicotine and nonsmokers using a paired occlusion protocol. In smokers, the RREP was measured after nicotine withdrawal, then with either nicotine or placebo gum, followed by the second RREP trial. Nonsmokers received only placebo gum. After nicotine withdrawal, the smokers had a higher state anxiety compared with nonsmokers. There was a significant interaction between groups (nonsmokers vs. smokers with nicotine vs. smokers with placebo) and test (pre- vs. posttreatment) in RREP N(1) peak amplitude S2/S1. The S2/S1 in the smokers were larger than in nonsmokers before treatment. After gum treatment, the smoker-with-placebo group had a significantly larger S2/S1 than the other two groups. The S2/S1 was significantly decreased after the administration of nicotine gum in smokers due to significantly decreased S2 amplitudes. The RREP N(f) and P(1) peaks were unaffected. These results demonstrated that respiratory sensory gating was decreased in smokers after nicotine withdrawal. Nicotine increased respiratory sensory gating in smokers with a S2/S1 similar to that of the nonsmokers. Nicotine did not change respiratory sensory information arrival, but secondary information processing in respiratory sensation.

Respiratory sensory gating measured by respiratory-related evoked potentials in generalized anxiety disorder

The perception of respiratory sensations plays an important role both in respiratory diseases and in anxiety disorders. However, little is known about the neural processes underlying respiratory sensory perception, especially in patient groups. Therefore, the present study examined whether patients with generalized anxiety disorder (GAD) would demonstrate altered respiratory sensory gating compared to a healthy control group. Respiratory-related evoked potentials (RREP) were measured in a paired inspiratory occlusion paradigm presenting two brief occlusion stimuli (S1 and S2) within one inspiration. The results showed a significantly greater S2/S1 ratio for the N1 component of the RREP in the GAD group compared to the control group. Our findings suggest altered respiratory sensory processing in patients with GAD, which might contribute to altered perception of respiratory sensations in these patients.

Respiratory perception measured by cortical neural activations in individuals with generalized anxiety disorder

There has been evidence for the effect of anxiety on the neural processing of respiratory sensation using the respiratory-related evoked potentials (RREP) elicited by inspiratory occlusions. This study tested the RREP elicited by inspiratory occlusions in a group of outpatients with generalized anxiety disorder (GAD) and a group of healthy controls. We hypothesized that the RREP P3 peak would be modulated in the GAD patients. A RREP oddball paradigm of 150-ms inspiratory occlusion protocol was used in 15 GAD patients and 11 healthy adults with normal lung functions. The RREP was recorded with a 40-channel electroencephalography (EEG) system. A minimum of 100 occlusions was collected for data analysis. We found that the averaged P3 latency of the GAD patients was significantly longer than the P3 latency of the healthy controls. In addition, the GAD group showed significantly reduced P3 amplitudes compared to the control group. No group differences in latency and amplitudes were found for earlier RREP components. These results demonstrated that a delayed and reduced attention peak (P3) is present in patients with GAD. This suggests that GAD as a disease state modulates the higher order processing of respiratory perception.

Reduced neural gating of respiratory sensations is associated with increased dyspnoea perception

According to the neural gating model of respiratory sensations, breathing occurs under normal conditions automatically without reaching consciousness (gating-out). This neural filter mechanism prevents the brain from being flooded with irrelevant respiratory sensations leaving sufficient neural processing capacities for everyday activities [1, 2]. However, in some circumstances, breathing can become conscious either voluntarily (e.g. attention, meditation) or due to increased respiratory demand (e.g. exacerbations, respiratory disease). In such cases, respiratory information is no longer filtered out but transmitted to higher brain centres which leads to the allocation of attentional resources towards the breathing sensation and brings it to conscious awareness (gating-in) [1, 2]. Similar to the neural gating in other modalities, such as auditory/visual/somatosensory gating [3, 4], this respiratory gating mechanism is, therefore, the neural basis for monitoring respiratory functioning and a pre-requisite for subsequent adaptive behaviour, such as medication intake or physician visits. Anxiety, which is prevalent in patients with dyspnoea [1, 5], has been shown to be associated with reduced neural gating of respiratory sensations, suggesting gating deficits to be a potential mechanism for the documented over-perception of dyspnoea in anxious individuals [6, 7]. The neural gating model of respiratory sensations implies that decreased neural gating of respiratory sensations is associated with increasing dyspnoea [4]. However, this implication has never been tested and was investigated in the present study by using respiratory-related evoked potentials (RREP) in the electroencephalogram (EEG) while additionally exploring potential effects of anxiety. Reduced respiratory neural gating is associated with increased dyspnoea, particularly in high anxious individuals http://ow.ly/xW4B30k34KR