The role of neuronal excitation and inhibition in the pre-Bötzinger complex on the cough reflex in the cat.

Brainstem respiratory neuronal network significantly contributes to cough motor pattern generation. Neuronal populations in the pre-Bötzinger complex (PreBötC) represent a substantial component for respiratory rhythmogenesis. We studied the role of PreBötC neuronal excitation and inhibition on mechanically induced tracheobronchial cough in 15 spontaneously breathing, pentobarbital anesthetized adult cats (35 mg/kg, iv initially). Neuronal excitation by unilateral microinjection of glutamate analog d,l-homocysteic acid resulted in mild reduction of cough abdominal electromyogram (EMG) amplitudes and very limited temporal changes of cough compared with effects on breathing (very high respiratory rate, high amplitude inspiratory bursts with a short inspiratory phase, and tonic inspiratory motor component). Mean arterial blood pressure temporarily decreased. Blocking glutamate-related neuronal excitation by bilateral microinjections of nonspecific glutamate receptor antagonist kynurenic acid reduced cough inspiratory and expiratory EMG amplitude and shortened most cough temporal characteristics similarly to breathing temporal characteristics. Respiratory rate decreased and blood pressure temporarily increased. Limiting active neuronal inhibition by unilateral and bilateral microinjections of GABAA receptor antagonist gabazine resulted in lower cough number, reduced expiratory cough efforts, and prolongation of cough temporal features and breathing phases (with lower respiratory rate). The PreBötC is important for cough motor pattern generation. Excitatory glutamatergic neurotransmission in the PreBötC is involved in control of cough intensity and patterning. GABAA receptor-related inhibition in the PreBötC strongly affects breathing and coughing phase durations in the same manner, as well as cough expiratory efforts. In conclusion, differences in effects on cough and breathing are consistent with separate control of these behaviors.NEW & NOTEWORTHY This study is the first to explore the role of the inspiratory rhythm and pattern generator, the pre-Bötzinger complex (PreBötC), in cough motor pattern formation. In the PreBötC, excitatory glutamatergic neurotransmission affects cough intensity and patterning but not rhythm, and GABAA receptor-related inhibition affects coughing and breathing phase durations similarly to each other. Our data show that the PreBötC is important for cough motor pattern generation, but cough rhythmogenesis appears to be controlled elsewhere.

Phrenic afferent activation modulates cardiorespiratory output in the adult rat.

Phrenic afferents project to brainstem areas responsible for cardiorespiratory control and the mid-cervical spinal cord containing the phrenic motor nucleus. Our purpose was to quantify the impact of small- and large-diameter phrenic afferent activation on phrenic motor output. Anesthetized and ventilated rats received unilateral phrenic nerve stimulation while contralateral phrenic motor output and blood pressure were recorded. Twelve currents of 40-Hz inspiratory-triggered stimulation were delivered (20 s on, 5 min off) to establish current response curves. Stimulation pulse width was varied to preferentially activate large-diameter phrenic afferents (narrow pulse width) and recruit small-diameter fibers (wide pulse width). Contralateral phrenic amplitude was elevated immediately poststimulation at currents above 35 µA for wide and 70 µA for narrow pulse stimulation when compared with animals not receiving stimulation (time controls). Wide pulse width stimulation also increased phrenic burst frequency at currents ≥35 µA, caused a transient decrease in mean arterial blood pressure at currents ≥50 µA, and resulted in a small change in heart rate at 300 µA. Unilateral dorsal rhizotomy attenuated stimulation-induced cardiorespiratory responses indicating that phrenic afferent activation is required. Additional analyses compared phrenic motor amplitude with output before stimulation and showed that episodic activation of phrenic afferents with narrow pulse stimulation can induce short-term plasticity. We conclude that the activation of phrenic afferents 1) enhances contralateral phrenic motor amplitude when large-diameter afferents are activated, and 2) when small-diameter fibers are recruited, the amplitude response is associated with changes in burst frequency and cardiovascular parameters.NEW & NOTEWORTHY Acute, inspiratory-triggered stimulation of phrenic afferents increases contralateral phrenic motor amplitude in adult rats. When small-diameter afferents are recruited, the amplitude response is accompanied by an increase in phrenic burst frequency, a transient decrease in mean arterial blood pressure, and a slight increase in heart rate. Repeated episodes of large-diameter phrenic afferent activation may also be capable of inducing short-term plasticity.

Microinjection of kynurenic acid in the rostral nucleus of the tractus solitarius disrupts spatiotemporal aspects of mechanically induced tracheobronchial cough.

The importance of neurons in the nucleus of the solitary tract (NTS) in the production of coughing was tested by microinjections of the nonspecific glutamate receptor antagonist kynurenic acid (kyn; 100 mM in artificial cerebrospinal fluid) in 15 adult spontaneously breathing anesthetized cats. Repetitive coughing was elicited by mechanical stimulation of the intrathoracic airway. Electromyograms (EMG) were recorded from inspiratory parasternal and expiratory transversus abdominis (ABD) muscles. Bilateral microinjections of kyn into the NTS rostral to obex [55 ± 4 nl total in 2 locations (n = 6) or 110 ± 4 nl total in 4 locations (n = 5)], primarily the ventrolateral subnucleus, reduced cough number and expiratory cough efforts (amplitudes of ABD EMG and maxima of esophageal pressure) compared with control. These microinjections also markedly prolonged the inspiratory phase, all cough-related EMG activation, and the total cough cycle duration as well as some other cough-related time intervals. In response to microinjections of kyn into the NTS rostral to the obex respiratory rate decreased, and there were increases in the durations of the inspiratory and postinspiratory phases and mean blood pressure. However, bilateral microinjections of kyn into the NTS caudal to obex as well as control vehicle microinjections in the NTS location rostral to obex had no effect on coughing or cardiorespiratory variables. These results are consistent with the existence of a critical component of the cough rhythmogenic circuit located in the rostral ventral and lateral NTS. Neuronal structures of the rostral NTS are significantly involved specifically in the regulation of cough magnitude and phase timing.NEW & NOTEWORTHY The nucleus of the solitary tract contains significant neuronal structures responsible for control of 1) cough excitability, 2) motor drive during cough, 3) cough phase timing, and 4) cough rhythmicity. Significant elimination of neurons in the solitary tract nucleus results in cough apraxia (incomplete and/or disordered cough pattern). The mechanism of the cough impairment is different from that for the concomitant changes in breathing.

Anatomy and physiology of phrenic afferent neurons.

Large-diameter myelinated phrenic afferents discharge in phase with diaphragm contraction, and smaller diameter fibers discharge across the respiratory cycle. In this article, we review the phrenic afferent literature and highlight areas in need of further study. We conclude that 1) activation of both myelinated and nonmyelinated phrenic sensory afferents can influence respiratory motor output on a breath-by-breath basis; 2) the relative impact of phrenic afferents substantially increases with diaphragm work and fatigue; 3) activation of phrenic afferents has a powerful impact on sympathetic motor outflow, and 4) phrenic afferents contribute to diaphragm somatosensation and the conscious perception of breathing. Much remains to be learned regarding the spinal and supraspinal distribution and synaptic contacts of myelinated and nonmyelinated phrenic afferents. Similarly, very little is known regarding the potential role of phrenic afferent neurons in triggering or modulating expression of respiratory neuroplasticity.

Rehabilitation of Swallowing and Cough Functions Following Stroke: An Expiratory Muscle Strength Training Trial.

OBJECTIVE: To determine the effect of expiratory muscle strength training (EMST) on both cough and swallow function in stroke patients. DESIGN: Prospective pre-post intervention trial with 1 participant group. SETTING: Two outpatient rehabilitation clinics. PARTICIPANTS: Adults (N=14) with a history of ischemic stroke in the preceding 3 to 24 months. INTERVENTION: EMST. The training program was completed at home and consisted of 25 repetitions per day, 5 days per week, for 5 weeks. MAIN OUTCOME MEASURES: Baseline and posttraining measures were maximum expiratory pressure, voluntary cough airflows, reflex cough challenge to 200µmol/L of capsaicin, sensory perception of urge to cough, and fluoroscopic swallow evaluation. Repeated measures and 1-way analyses of variance were used to determine significant differences pre- and posttraining. RESULTS: Maximum expiratory pressure increased in all participants by an average of 30cmH2O posttraining. At baseline, all participants demonstrated a blunted reflex cough response to 200µmol/L of capsaicin. After 5 weeks of training, measures of urge to cough and cough effectiveness increased for reflex cough; however, voluntary cough effectiveness did not increase. Swallow function was minimally impaired at baseline, and there were no significant changes in the measures of swallow function posttraining. CONCLUSIONS: EMST improves expiratory muscle strength, reflex cough strength, and urge to cough. Voluntary cough and swallow measures were not significantly different posttraining. It may be that stroke patients benefit from the training for upregulation of reflex cough and thus improved airway protection.

Comparison of Two Methods for Inducing Reflex Cough in Patients With Parkinson's Disease, With and Without Dysphagia.

Aspiration pneumonia is a common cause of death in people with Parkinson's disease (PD). Dysfunctional swallowing occurs in the majority of people with PD, and research has shown that cough function is also impaired. Previous studies suggest that testing reflex cough by having participants inhale a cough-inducing stimulus through a nebulizer may be a reliable indicator of swallowing dysfunction, or dysphagia. The primary goal of this study was to determine the cough response to two different cough-inducing stimuli in people with and without PD. The second goal of this study was to compare the cough response to the two different stimuli in people with PD, with and without swallowing dysfunction. Seventy adults (49 healthy and 21 with PD) participated in the study. Aerosolized water (fog) and 200 µM capsaicin were used to induce cough. Each substance was placed in a small, hand-held nebulizer, and presented to the participant. Each cough stimulus was presented three times. The total number of coughs produced to each stimulus trial was recorded. All participants coughed more to capsaicin versus fog (p < 0.001). A categorical 'responder' and 'non-responder' variable for the fog stimulus, defined as whether or not the participant coughed at least two times to two of three presentations of the stimulus, yields sensitivity of 77.8 % and a specificity of 90.9 % for identifying PD participants with and without dysphagia. The data show a differential response of the PD participants to the capsaicin versus fog stimuli. Clinically, this finding may allow for earlier identification of people with PD who are in need of a swallowing evaluation. As well, there are implications for the neural control of cough in this patient population.

Role of the dorsal medulla in the neurogenesis of airway protection.

The dorsal medulla encompassing the nucleus of the tractus solitarius (NTS) and surrounding reticular formation (RF) has an important role in processing sensory information from the upper and lower airways for the generation and control of airway protective behaviors. These behaviors, such as cough and swallow, historically have been studied in isolation. However, recent information indicates that these and other airway protective behaviors are coordinated to minimize risk of aspiration. The dorsal medullary neural circuits that include the NTS are responsible for rhythmogenesis for repetitive swallowing, but previous models have assigned a role for this portion of the network for coughing that is restricted to monosynaptic sensory processing. We propose a more complex NTS/RF circuit that controls expression of swallowing and coughing and the coordination of these behaviors. The proposed circuit is supported by recordings of activity patterns of selected neural elements in vivo and simulations of a computational model of the brainstem circuit for breathing, coughing, and swallowing. This circuit includes separate rhythmic sub-circuits for all three behaviors. The revised NTS/RF circuit can account for the mode of action of antitussive drugs on the cough motor pattern, as well as the unique coordination of cough and swallow by a meta-behavioral control system for airway protection.

Effect of laparotomy on the swallow-breathing relationship in the cat.

Swallow occurs predominantly in the expiratory phase (E) of breathing. This phase preference is thought to contribute to airway protection by limiting the passage of material through the pharyngeal airway with little or no inspiratory (I) airflow. This phase preference is attributed to central interactions between the swallow and breathing pattern generators. We speculated that changes in peripheral mechanical factors would influence the respiratory phase preference for swallow initiation. We induced swallowing in anesthetized spontaneously breathing cats by injection of water into the oropharynx. In animals with intact abdomens, 83 % of swallows were initiated during E, 7 % during I, 7 % during E-I phase transition, and 3 % during I-E transition. In animals with open anterior midline laparotomy, only 38 % of swallows were initiated during E, 33 % during I, 17 % during the E-I transition, and 12 % during I-E. The results support an important role for feedback from somatic and/or visceral thoraco-abdominal mechanoreceptors for swallow-breathing coordination after laparotomy.

Respiratory and auditory cortical processing in children with obstructive sleep apnea syndrome.

RATIONALE: Children with obstructive sleep apnea syndrome (OSAS) have impaired cortical processing of respiratory afferent stimuli, manifested by blunted sleep respiratory-related evoked potentials (RREP). However, whether this impairment is limited to respiratory stimuli, or reversible after successful treatment, is unknown. We hypothesized that, during sleep, children with OSAS have (1) abnormal RREP, (2) normal cortical processing of nonrespiratory stimuli, and (3) persistence of abnormal RREP after treatment. OBJECTIVES: To measure sleep RREP and auditory evoked potentials in normal control subjects and children with OSAS before and after treatment. METHODS: Twenty-four children with OSAS and 24 control subjects were tested during N3 sleep. Thirteen children with OSAS repeated testing 4-6 months after adenotonsillectomy. MEASUREMENTS AND MAIN RESULTS: RREP were blunted in OSAS compared with control subjects (N350 at Cz -27 ± 15.5 vs. -47.4 ± 28.5 µV; P = 0.019), and did not improve after OSAS treatment (N350 at Cz pretreatment -25.1 ± 7.4 vs. -29.8 ± 8.1 post-treatment). Auditory evoked potentials were similar in OSAS and control subjects at baseline (N350 at Cz -58 ± 33.1 vs. -66 ± 31.1 µV), and did not change after treatment (N350 at Cz -67.5 ± 36.8 vs. -65.5 ± 20.3). CONCLUSIONS: Children with OSAS have persistent primary or irreversible respiratory afferent cortical processing deficits during sleep that could put them at risk of OSAS recurrence. OSAS does not seem to affect the cortical processing of nonrespiratory (auditory) afferent stimuli during sleep.

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.

Translating the Interplay of Cognition and Physical Performance in COPD and Interstitial Lung Disease: Meeting Report and Literature Review.

TOPIC IMPORTANCE: Cognitive and physical limitations are common in individuals with chronic lung diseases, but their interactions with physical function and activities of daily living are not well characterized. Understanding these interactions and potential contributors may provide insights on disability and enable more tailored rehabilitation strategies. REVIEW FINDINGS: This review summarizes a 2-day meeting of patient partners, clinicians, researchers, and lung associations to discuss the interplay between cognitive and physical function in people with chronic lung diseases. This report covers four areas: (1) cognitive-physical limitations in patients with chronic lung diseases; (2) cognitive assessments; (3) strategies to optimize cognition and motor control; and (4) future research directions. Cognitive and physical impairments have multiple effects on quality of life and daily function. Meeting participants acknowledged the need for a standardized cognitive assessment to complement physical assessments in patients with chronic lung diseases. Dyspnea, fatigue, and age were recognized as important contributors to cognition that can affect motor control and daily physical function. Pulmonary rehabilitation was highlighted as a multidisciplinary strategy that may improve respiratory and limb motor control through neuroplasticity and has the potential to improve physical function and quality of life. SUMMARY: There was consensus that cognitive function and the cognitive interference of dyspnea in people with chronic lung diseases contribute to motor control impairments that can negatively affect daily function, which may be improved with pulmonary rehabilitation. The meeting generated several key research questions related to cognitive-physical interactions in individuals with chronic lung diseases.

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.

fNIRS analysis of rostral prefrontal cortex activity and perception of inspiratory loads.

It is well-established that the brainstem is responsible for the automatic control of breathing, however, cortical areas control perception and conscious breathing. This study investigated activity in the prefrontal cortex (PFC) during breathing difficulty using functional near-infrared spectroscopy (fNIRS). It was hypothesized that extrinsic inspiratory loads will elicit regional changes in PFC activity and increased perception ratings, as a function of load magnitude and type. Participants were exposed to varying magnitudes of resistive (R) and pressure threshold (PT) inspiratory loads to increase breathing effort. Perception ratings of breathing effort and load magnitude were positively correlated (p < 0.05). PT loads were rated more effortful than R loads (p < 0.05). Differences in perceived effort were a function of inspiratory pressure-time-product (PTP) and inspiratory work of breathing (WoB). PFC activity increased with the largest PT load (p < 0.01), suggesting that the PFC is involved in processing respiratory stimuli. The results support the hypothesis that the PFC is an element of the neural network mediating effortful breathing perception.

Primary site of constriction during the compression phase of cough in healthy young adults.

Glottal closure has been considered as the primary constriction point during the compression phase (CP); however, vocal fold adduction alone cannot resist the high pressures, providing motivation to explore other mechanisms contributing to that resistance. The goal of this study was to identify site(s) and degree of constriction during the CP of cough of varying types in healthy young adults. Twenty-five healthy young participants participated in this study. The experimental protocol was comprised of: 1) baseline pulmonary function measures; 2) cough practice to establish weak, moderate and strong coughs; 3) voluntary and reflex cough assessments with fluoroscopy and airflow measures. We used a repeated measures ANOVA to identify whether there are differences in constriction ratio between cough types. There was a significant difference in constriction of varying cough types. Degree of constriction in all cough strengths showed that the glottis was the most constricted area, followed by the laryngeal vestibule, nasopharynx, hypopharynx, oropharynx, and cervical trachea, in order, but stronger cough resulted in more constriction in all areas compared to weaker cough. Degree of constriction in reflex cough showed a similar pattern though there was greater constriction in the oropharynx than the hypopharynx. Airflow measures in voluntary cough were consistent with previous findings. Differences in upper airway constriction during the compression phase of cough may be attributed to differences in motor control between reflex and voluntary cough, and the increased constriction seen during strong cough may reflect increased muscle recruitment during that task. In the future, we can use this knowledge to develop novel methods for cough rehabilitation.

Effects of emotional contexts on respiratory attention task performance.

Negative emotions have been found associated with high prevalence of respiratory disease and increased subjective feelings of dyspnea, while positive emotional stimulus has been suggested to alleviate dyspneic feelings. However, the extent to which different emotional contexts affect individuals' respiratory interoceptive attention was not clear. Therefore, the purpose of this study was to investigate the influences of emotional contexts on respiratory interoceptive accuracy, and the relationships between respiratory interoceptive accuracy and negative emotions as well as respiratory symptoms. Fifty-six healthy participants completed the self-reported questionnaires of depression, anxiety, and respiratory symptoms. During the experiment, the participants were instructed to watch one neutral and one positive affective picture series and mentally count the number of perceived occlusions (reported at the end of the trials). The Wilcoxon Signed-Rank test and Spearman's correlations were used to examine the effect of the emotional pictures and to explore the relationships between the level of emotional status or respiratory symptoms and respiratory interoceptive task performance. The significance level was set at p < 0.05. Our results did not show a significant difference in participants' occlusion counting task performance between the neutral and positive emotional context. However, Spearman's Rho correlation analysis revealed that depression level was negatively correlated with accuracy of the task performance in the neutral emotional context, and this relationship diminished in the positive emotional context. In summary, our study demonstrated that negative emotional status, especially depression, may lead to decreased respiratory interoceptive accuracy. Future studies are recommended to test the effect of positive emotional context on respiratory interoceptive task performance in individuals with clinical depression and anxiety.

Three-dimensional models of the equine larynx can be used to perform traditional measures of arytenoid abduction and permit the positioning of modeled implants to demonstrate the anatomic feasibility of placing a rigid implant across the cricoarytenoid joint.

OBJECTIVE: To develop 3D models of larynges to compare arytenoid abduction measurements between specimens and models, and to investigate the anatomic feasibility of placing an implant across the cricoarytenoid joint (CAJ) with or without arthrotomy. SAMPLES: Cadaveric equine larynges (n = 9). PROCEDURES: Equine larynges underwent sequential CT scans in a neutral position and with 2 arytenoid treatments: bilateral arytenoid abduction (ABD) and bilateral arytenoid abduction after left cricoarytenoid joint arthrotomy (ARTH). Soft tissue, cartilage, and luminal volume 3-dimensional models were generated. Rima glottidis cross-sectional area (CSA) and left-to-right quotient (LRQ) angles were measured on laryngeal specimens and models. Arytenoid translation, articular contact area, and length of modeled implants placed across the CAJ were measured on models. Data were analyzed using paired t test or ANOVA and Tukey's post hoc test or non-parametric equivalents (P < .05). RESULTS: ARTH CSA was larger for laryngeal specimens than models (P = .0096). There was no difference in all other measures of CSA and LRQ angle between treatment groups or between specimens and models. There was no difference between ABD and ARTH groups for arytenoid cartilage translation, contact area, and implant length. The articular contact area was sufficient for modeled implant placement across the CAJ with a narrow range of implant lengths (17.59 mm to 23.87 mm) across larynges with or without arthrotomy. CLINICAL RELEVANCE: These results support further investigation of a CT-guided, minimally invasive surgical procedure. Future studies will evaluate the outcomes of the new procedure for technical precision, biomechanical stability, and post-operative success rates for horses with recurrent laryngeal neuropathy (RLN).

Respiratory psychophysiology and COVID-19: A research agenda.

After multiple waves of the COVID-19 pandemic, it has become clear that the impact of SARS-CoV-2 will carry on for years to come. Acutely infected patients show a broad range of disease severity, depending on virus variant, vaccination status, age and the presence of underlying medical and physical conditions, including obesity. Additionally, a large number of patients who have been infected with the virus present with post-COVID syndrome. In September 2020, the International Society for the Advancement of Respiratory Psychophysiology organized a virtual interest meeting on 'Respiratory research in the age of COVID-19', which aimed to discuss how research in respiratory psychophysiology could contribute to a better understanding of psychophysiological interactions in COVID-19. In the resulting current paper, we propose an interdisciplinary research agenda discussing selected research questions on acute and long-term neurobiological, physiological and psychological outcomes and mechanisms related to respiration and the airways in COVID-19, as well as research questions on comorbidity and potential treatment options, such as physical rehabilitation.

Failure to breathe persists without air hunger or alarm following amygdala seizures.

Postictal apnea is thought to be a major cause of sudden unexpected death in epilepsy (SUDEP). However, the mechanisms underlying postictal apnea are unknown. To understand causes of postictal apnea, we used a multimodal approach to study brain mechanisms of breathing control in 20 patients (ranging from pediatric to adult) undergoing intracranial electroencephalography for intractable epilepsy. Our results indicate that amygdala seizures can cause postictal apnea. Moreover, we identified a distinct region within the amygdala where electrical stimulation was sufficient to reproduce prolonged breathing loss persisting well beyond the end of stimulation. The persistent apnea was resistant to rising CO2 levels, and air hunger failed to occur, suggesting impaired CO2 chemosensitivity. Using es-fMRI, a potentially novel approach combining electrical stimulation with functional MRI, we found that amygdala stimulation altered blood oxygen level-dependent (BOLD) activity in the pons/medulla and ventral insula. Together, these findings suggest that seizure activity in a focal subregion of the amygdala is sufficient to suppress breathing and air hunger for prolonged periods of time in the postictal period, likely via brainstem and insula sites involved in chemosensation and interoception. They further provide insights into SUDEP, may help identify those at greatest risk, and may lead to treatments to prevent SUDEP.

On the psychology of cough.

Neurobiological research is increasingly documenting the role of higher brain areas in cough, but little systematic behavioral research on the role of psychological factors exists. In this article we discuss the role of perceptual, attentional, cognitive, and emotional factors, learning mechanisms, self-regulation, and the role of social context. We also describe how interactions among these mechanisms can help to shed light on idiopathic cough and on placebo/nocebo effects on cough. This functional-behavioral perspective may lay the groundwork for a structured research program on the role of psychological factors in cough.

Using the "visual target grip test" to identify sincerity of effort during grip strength testing.

UNLABELLED: We devised a sincerity of effort assessment based on "tricking" a person into exerting maximal effort by providing incorrect visual feedback. The assessment involves deriving a target line from nonvisual peak gripping force, instructing participants to reach it with each grip repetition, and then secretly changing its position, which requires doubling the force necessary to reach it. Accordingly, participants are tricked into exerting more force than intended to reach the deceptive target line. We examined the validity of this test by comparing force values between "trick" and "non-trick" trials in 30 healthy participants. The study design used was a prospective cohort. Providing incorrect visual feedback caused significantly greater increases in force during submaximal effort (69%) than during maximal effort (28%). This test effectively detected submaximal effort (sensitivity=0.83 and specificity=0.93). Although this test is not safe for patients during initial therapy, it may be appropriate for patients who can safely exert maximal grip force. LEVEL OF EVIDENCE: Not applicable.