Neural mechanisms of respiratory interoception.

Respiratory interoception is one of the internal bodily systems that is comprised of different types of somatic and visceral sensations elicited by different patterns of afferent input and respiratory motor drive mediating multiple respiratory modalities. Respiratory interoception is a complex system, having multiple afferents grouped into afferent clusters and projecting into both discriminative and affective centers that are directly related to the behavioral assessment of breathing. The multi-afferent system provides a spectrum of input that result in the ability to interpret the different types of respiratory interceptive sensations. This can result in a response, commonly reported as breathlessness or dyspnea. Dyspnea can be differentiated into specific modalities. These respiratory sensory modalities lead to a general sensation of an Urge-to-Breathe, driven by a need to compensate for the modulation of ventilation that has occurred due to factors that have affected breathing. The multiafferent system for respiratory interoception can also lead to interpretation of the sensory signals resulting in respiratory related sensory experiences, including the Urge-to-Cough and Urge-to-Swallow. These behaviors are modalities that can be driven through the differentiation and integration of multiple afferent input into the respiratory neural comparator. Respiratory sensations require neural somatic and visceral interoceptive elements that include gated attention and detection leading to respiratory modality discrimination with subsequent cognitive decision and behavioral compensation. Studies of brain areas mediating cortical and subcortical respiratory sensory pathways are summarized and used to develop a model of an integrated respiratory neural network mediating respiratory interoception.

Longitudinal changes in health-related quality of life in preschool children with cerebral palsy of different levels of motor severity.

BACKGROUND: When setting goals for cerebral palsy (CP) interventions, health-related quality of life (HRQoL) is an important outcome. AIMS: To compare longitudinal changes in HRQoL in children with CP of different levels of motor severity. METHODS AND PROCEDURES: Seventy-three children with CP were collected and classified into three groups based on Gross Motor Function Classification System (GMFCS) levels. HRQoL was assessed by parent's proxy of the TNO-AZL Preschool Quality of Life (TAPQOL) at baseline and 6 months later. OUTCOMES AND RESULTS: Children with GMFCS level V had a lower total TAPQOL score and scores in all domains than those with level I-IV (p<0.01), except for the non-motor subdomain of physical functioning at follow-up. With regards to longitudinal changes, the children with GMFCS level V had greater improvements in physical (p=0.016) and cognitive functioning (p=0.042), but greater deterioration in emotional functioning (p=0.008) than those with levels I-II at 6 months of follow-up. CONCLUSIONS AND IMPLICATIONS: Motor severity was associated with TAPQOL scores in all domains and changes in some domains in children with CP. Clinicians should early identify children at risk of a poor HRQoL and plan timely treatment strategies to enhance the HRQoL of children with CP.

Effect of deep pressure input on parasympathetic system in patients with wisdom tooth surgery.

BACKGROUND/PURPOSE: Deep pressure input is used to normalize physiological arousal due to stress. Wisdom tooth surgery is an invasive dental procedure with high stress levels, and an alleviation strategy is rarely applied during extraction. In this study, we investigated the effects of deep pressure input on autonomic responses to wisdom tooth extraction in healthy adults. METHODS: A randomized, controlled, crossover design was used for dental patients who were allocated to experimental and control groups that received treatment with or without deep pressure input, respectively. Autonomic indicators, namely the heart rate (HR), percentage of low-frequency (LF) HR variability (LF-HRV), percentage of high-frequency (HF) HRV (HF-HRV), and LF/HF HRV ratio (LF/HF-HRV), were assessed at the baseline, during wisdom tooth extraction, and in the posttreatment phase. RESULTS: Wisdom tooth extraction caused significant autonomic parameter changes in both groups; however, differential response patterns were observed between the two groups. In particular, deep pressure input in the experimental group was associated with higher HF-HRV and lower LF/HF-HRV during extraction compared with those in the control group. CONCLUSION: LF/HF-HRV measurement revealed balanced sympathovagal activation in response to deep pressure application. The results suggest that the application of deep pressure alters the response of HF-HRV and facilitates maintaining sympathovagal balance during wisdom tooth extraction.

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.

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-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.

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.

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.