Hsiu-Wen Tsai

Negative emotional stimulation decreases respiratory sensory gating in healthy humans

We tested the hypothesis that negative emotions decrease the respiratory-related evoked potentials (RREP) sensory gating (RSG). RREP were elicited by paired inspiratory occlusions. RSG was calculated as the difference in the averaged RREP peak N1 amplitude between the second (S2) and the first occlusion (S1). RSG was compared between unpleasant and neutral emotional conditions elicited by viewing affective pictures from the IAPS system in thirteen healthy adults. Results are expressed as median [min; max]. Compared to neutral pictures, viewing unpleasant pictures decreased the RREP N1(S1) amplitude (-3.37 μV [-4.62; -1.37] versus -4.59 μV [-6.08; -1.36]; p=0.017) but not the RREP N1(S2) amplitude (-0.26 [-3.24; 2.36] versus -0.7 [-1.54; 3.6]; p = 0.68), and reduced the difference score S2-S1 (3.73 μV [0; 5.82] versus 4.79 μV [3; 6.2]; p = 0.038). We concluded that a negative emotional stimulation could attract subjects attention to the detriment of the respiratory sensory inputs and produced an overall decrease in the RSG. This latter finding might participate in an over-perception of repeatedly presented respiratory stimuli.

The impact of emotion on the perception of graded magnitudes of respiratory resistive loads

Emotional state can modulate the perception of respiratory loads but the range of respiratory load magnitudes affected by emotional state is unknown. We hypothesized that viewing pleasant, neutral and unpleasant affective pictures would modulate the perception of respiratory loads of different load magnitudes. Twenty-four healthy adults participated in the study. Five inspiratory resistive loads of increasing magnitude (5, 10, 15, 20, 45 cm H(2)O/L/s) were repeatedly presented for one inspiration while participants viewed pleasant, neutral and unpleasant affective picture series. Participants rated how difficult it was to breathe against the load immediately after each presentation. Only at the lowest load, magnitude estimation ratings were greater when subjects viewed the unpleasant series compared to the neutral and pleasant series. These results suggest that negative emotional state increases the sense of respiratory effort for single presentations of a low magnitude resistive load but high magnitude loads are not further modulated by emotional state.

Respiratory responses following blast-induced traumatic brain injury in rats.

Blast overpressure (OB) injury in rodents has been employed for modeling the traumatic brain injury (TBI) induced by an improvised explosive device (IED) in military service personnel. IEDs can cause respiratory arrest if directed at the thorax due to the fluid-tissue interface of the lungs but it is unclear what respiratory changes occur in a head-directed OB injury. The diaphragm is the primary muscle of inspiration and electromyographic (EMG) recordings from this muscle are used for recording breathing in anesthetized and conscious rats. The breathing pattern of the rodents will be recorded during the OB injury. Our results indicate that a dorsal directed closed-head OB injury results in a neurally mediated apnea followed by respiratory timing changes.

Preliminary Evidence of Reduced Urge to Cough and Cough Response in Four Individuals following Remote Traumatic Brain Injury with Tracheostomy

Cough and swallow protect the lungs and are frequently impaired following traumatic brain injury (TBI). This project examined cough response to inhaled capsaicin solution challenge in a cohort of four young adults with a history of TBI within the preceding five years. All participants had a history of tracheostomy with subsequent decannulation and dysphagia after their injuries (resolved for all but one participant). Urge to cough (UTC) and cough response were measured and compared to an existing database of normative cough response data obtained from 32 healthy controls (HCs). Participants displayed decreased UTC and cough responses compared to HCs. It is unknown if these preliminary results manifest as a consequence of disrupted sensory (afferent) projections, an inability to perceive or discriminate cough stimuli, disrupted motor (efferent) response, peripheral weakness, or any combination of these factors. Future work should attempt to clarify if the observed phenomena are borne out in a larger sample of individuals with TBI, determine the relative contributions of central versus peripheral nervous system structures to cough sensory perceptual changes following TBI (should they exist), and formulate recommendations for systematic screening and assessment of cough sensory perception in order to facilitate rehabilitative efforts. This project is identified with the National Clinical Trials NCT02240329.

The effect of tracheal occlusion on respiratory load compensation: Changes in neurons containing inhibitory neurotransmitter in the nucleus of the solitary tract in conscious rats

Respiratory load compensation volume-time (Vt-T) relationships have been extensively studied in anesthetized animals. There are only a few studies in conscious animals although consciousness and behavior play a critical role in modulation of breathing. The aims of the study were to determine the effect of intermittent and transient tracheal occlusions (ITTO) elicited load compensation responses and the changes in activation of inhibitory glycinergic neurons in the nucleus of solitary tract (NTS) in conscious rats. The results showed that ITTO elicited an increase in expiratory time (T(e)) but did not affect inspiratory time (T(i)) and diaphragm activity (EMG(dia)). An increase in total breathing time (Ttot) was due exclusively to the increase in T(e). In addition, glycinergic neurons were activated in the intermediate NTS (iNTS) but not in the caudal NTS (cNTS). These results suggest that the activated glycinergic neurons in the iNTS may be important for the neurogenesis of load compensation responses in conscious animals.

Tracheal occlusion-evoked respiratory load compensation and inhibitory neurotransmitter expression in rats

Respiratory load compensation is a sensory-motor reflex generated in the brain stem respiratory neural network. The nucleus of the solitary tract (NTS) is thought to be the primary structure to process the respiratory load-related afferent activity and contribute to the modification of the breathing pattern by sending efferent projections to other structures in the brain stem respiratory neural network. The sensory pathway and motor responses of respiratory load compensation have been studied extensively; however, the mechanism of neurogenesis of load compensation is still unknown. A variety of studies has shown that inhibitory interconnections among the brain stem respiratory groups play critical roles for the genesis of respiratory rhythm and pattern. The purpose of this study was to examine whether inhibitory glycinergic neurons in the NTS were activated by external and transient tracheal occlusions (ETTO) in anesthetized animals. The results showed that ETTO produced load compensation responses with increased inspiratory, expiratory, and total breath time, as well as elevated activation of inhibitory glycinergic neurons in the caudal NTS (cNTS) and intermediate NTS (iNTS). Vagotomized animals receiving transient respiratory loads did not exhibit these load compensation responses. In addition, vagotomy significantly reduced the activation of inhibitory glycinergic neurons in the cNTS and iNTS. The results suggest that these activated inhibitory glycinergic neurons in the NTS might be essential for the neurogenesis of load compensation responses in anesthetized animals.

Neurons in the dorsomedial medulla contribute to swallow pattern generation: Evidence of inspiratory activity during swallow

Active contraction of the diaphragm and other inspiratory pump muscles during swallow create a negative thoracic pressure to improve the movement of the bolus (food/liquid) into the esophagus. We tested the hypothesis that dorsomedial medullary inspiratory neurons, including the nucleus tractus solitarius (NTS, pre-motor to the phrenic) would be active during swallow induced by oral water infusion. We recorded neurons in the NTS and medial reticular formation in anesthetized spontaneously breathing cats, and induced swallow by injection of water into the oropharynx. Our results indicate that: 1) a majority of inspiratory cells in the dorsomedial medulla are active during swallow, 2) expiratory neurons are present in the medial reticular formation (deeper to the NTS) in unparalyzed cats and a majority of these cells decreased firing frequency during swallow. Our findings suggest that the dorsomedial medulla is a source of inspiratory motor drive during swallow and that a novel population of breathing-modulated neurons that also are modulated during swallowing exist in the medial reticular formation in unparalyzed animals.

Cough physiology in elderly women with nontuberculous mycobacterial lung infections

Elderly white, thin, nonsmoking women appear to be more susceptible to lung infections with Mycobacterium avium complex and other nontuberculous mycobacteria (NTM). It has been postulated that such disease in women is related to suppression of their cough. We hypothesized that patients with pulmonary NTM (pNTM) infections may have altered cough physiology compared with unaffected control subjects. We used capsaicin-induced cough to assess the cough reflex in pNTM subjects. Eight elderly white women with stable chronic pNTM infections and six unaffected age-matched control subjects were recruited. There was no significant difference between groups in capsaicin-elicited cough motor response, airflow pattern, or cough frequency. The urge-to-cough (UTC) score at the lowest capsaicin concentration was significantly lower in pNTM than control subjects (P < 0.05). There were no significant differences in the UTC score between pNTM and control subjects at >50 μM capsaicin. These results suggest lower UTC sensitivity to the lowest concentration of capsaicin in pNTM than control subjects. In other words, the pNTM subjects do not sense a UTC when the stimulus is relatively small.NEW & NOTEWORTHY This study investigates the cough motor response and cough sensitivity in patients with nontuberculous mycobacteria (NTM) infection. In elderly white female pulmonary NTM subjects, we demonstrated a capacity to produce coughs similar to that of age-matched control subjects but decreased cough sensitivity in response to a low dose of capsaicin compared with control subjects. These findings are important to understand the pathophysiological mechanisms resulting in NTM disease in elderly white women and/or the syndrome developing in elderly white female NTM patients.

Somatomotor and Behavioral Changes Following Traumatic Brain Injury

Overpressurization blast (OB) exposure used to induce traumatic brain injury (TBI) in the rodent model can result in somatomotor and behavioral changes. Increased anxiety is evidenced after OB TBI in Dorsal and Frontal blast-wave exposed injured animals. Sustained impaired somatosensory functions occur after multiple OB injuries in Dorsal animals. Somatomotor function is impaired acutely but partially recovers after OB injury in Frontal animals. The Dorsal Group had reduction in risk-taking behavior in Group 1 (low pressure OB) and in total exploration in Group 2 (high pressure OB). The critical time point for somatosensory and somatomotor function impairment occurs at 24 hours post-OB injury with Group 1 demonstrating somatosensory and Group 2 demonstrating somatomotor deficits. The results suggest orientation and pressure magnitude have a significant impact on behavioral outcome measures following OB injuries as well as cumulative ef fects of repeated OB.

Optimizing an Internal Airway Percussion Device for Facilitating Exhalate Diagnostics of the Human Respiratory System

PURPOSE There is an urgent need for simple, inexpensive, noninvasive, and repeatable technique for the diagnosis of pulmonary diseases. Bronchoalveolar lavage, which is the gold standard diagnostic method for pulmonary diseases, does not meet any of these criteria. This study seeks to develop and optimize a novel technique of Internal Airway Percussion (IAP) to facilitate the collection and characterization of human respiratory system exhalates. METHODS The IAP device transmits sound waves into the respiratory tract, thereby increasing the release of aerosolized particles within exhaled breath by vibrating both lungs. Nine combinations of sound wave frequencies and amplitudes were studied to determine optimal frequency and amplitude combination for maximum aerosol particle gain in healthy human subjects. RESULTS Square-shaped sound waves generated at 15 Hz and 3 cm H2O resulted in 15 times greater total mass of collected particles in the first 2 min of sampling, and 1.2 to 1.5 times increase in count median diameter of the particles. CONCLUSIONS IAP, optimized at the frequency of 15 Hz and the pressure amplitude of 3 cm H2O, increased the total mass of particles exhaled from the human respiratory system. IAP has a broad range of potential clinical applications for noninvasive diagnosis of lung diseases including asthma, cystic fibrosis, pneumonia, and lung cancer, along with improvement of mucus clearance.