Investigation of the Neural Control of Cough and Cough Suppression in Humans Using Functional Brain Imaging

Abstract

Excessive coughing is one of the most common reasons for seeking medical advice, yet the available therapies for treating cough disorders are inadequate. Humans can voluntarily cough, choose to suppress their cough, and are acutely aware of an irritation that is present in their airways. This indicates a significant level of behavioral and conscious control over the basic cough reflex pathway. However, very little is known about the neural basis for higher brain regulation of coughing. The aim of the present study was to use functional brain imaging in healthy humans to describe the supramedullary control of cough and cough suppression. Our data show that the brain circuitry activated during coughing in response to capsaicin-evoked airways irritation is not simply a function of voluntarily initiated coughing and the perception of airways irritation. Rather, activations in several brain regions, including the posterior insula and posterior cingulate cortex, define the unique attributes of an evoked cough. Furthermore, the active suppression of irritant-evoked coughing is also associated with a unique pattern of brain activity, including an involvement of the anterior insula, anterior mid-cingulate cortex, and inferior frontal gyrus. These data demonstrate for the first time that evoked cough is not solely a brainstem-mediated reflex response to irritation of the airways, but rather requires active facilitation by cortical regions, and is further regulated by distinct higher order inhibitory processes.

Overdrinking, swallowing inhibition, and regional brain responses prior to swallowing

“…Preprocessing and analysis of functional images was performed using standard procedures with FEAT, version 4.1.9 (75). Regressors for rating, liquid in the mouth, and swallowing events were included in the model, which also incorporated the confound regressors related to head motion and physiological noise produced by respiratory maneuvers during swallowing (76,77). A regression analysis was performed for the oversated condition by using the mean of each participant's effort and pleasantness ratings as independent regressors to explain brain activity during the preswallow period.…”

Measuring voluntary and reflexive cough strength in healthy individuals

“…It is still unclear which of these three receptors, individually or collectively, are responsible for the elicitation of the RC and precisely how they work together to regulate it (Canning, 2006;Haji et al, 2013). Mazzone, Cole, Ando, Egan, & Farrell (2011) investigated neurological control of VC, non-evoked suppressed coughing (where participants were instructed not to cough and coughing was completely suppressed) and evoked cough reflex (where participants were instructed to cough whilst breathing in capsaicin) in healthy individuals undergoing fMRI.…”

“…Furthermore, VC is predominantly cortically controlled whereas RC is controlled by the rostral and caudal medulla (Mazzone et al, 2011). This implies that neurological impairment could result in very different outcomes for VC versus RC as shown by Fontana et al (1998) who found that RC was more impaired than VC in patients with Parkinson's disease.…”

An update and systematic review on drug therapies for the treatment of refractory chronic cough

“…Distinct higher brain circuitry for facilitating and suppressing the cough reflex has been visualized by functional magnetic resonance imaging (fMRI) [22]. CHS is associated with hypersensitivity of the larynx and upper airway and is often diagnosed by clinical history [23] and sometimes through quantitative sensory testing such as with hypertonic saline challenge, transnasal laryngoscopy with odor provocation, and cough reflex sensitivity testing with capsaicin [7,8].…”

“…The most pronounced effect was a reduction in stimulus-induced brain deactivation following central sensitization. In cough, Mazzone et al [22] investigated the neural control of cough and cough suppression in healthy humans with capsaicin-evoked cough using fMRI. These studies have confirmed the existence of distinct higher brain circuitry for facilitating and suppressing the cough reflex and provide novel insights into the supramedullary control of cough in humans.…”