Conditioned respiratory threat in the subdivisions of the human periaqueductal gray

Abstract

The sensation of breathlessness is the most threatening symptom of respiratory disease. The different subdivisions of the midbrain periaqueductal gray (PAG) are intricately (and differentially) involved in integrating behavioural responses to threat in animals, while the PAG has previously only been considered as a single entity in human research. Here we investigate how these individual PAG columns are differently involved with respiratory threat. Eighteen healthy subjects were conditioned to associate shapes with certain or uncertain impending respiratory load, and scanned the following day during anticipation and application of inspiratory loading using 7 T functional MRI. We showed activity in the ventrolateral PAG (vlPAG) during anticipation of resistive loading, with activity in the lateral PAG (lPAG) during resistive loading, revealing spatially and temporally distinct functions within this structure. We propose that lPAG is involved with sensorimotor responses to breathlessness, while the vlPAG operates within the threat perception network for impending breathlessness.DOI: http://dx.doi.org/10.7554/eLife.12047.001

Dyspnea catastrophizing and neural activations during the anticipation and perception of dyspnea

“…which were reported in two studies using pain stimuli and included the amygdala, prefrontal areas, and sensory cortices (Loggia et al, 2015;Seminowicz & Davis, 2006). In addition, neither during the anticipation nor during the perception of dyspnea were significant correlations of dyspnea catastrophizing observed with activations in insula and amygdala, although these areas were activated in previous studies during anticipated and perceived dyspnea (Davenport & Vovk, 2009;Evans, 2010;Faull et al, 2016;Herigstad et al, 2011), including the original study of Subsample 2 (Stoeckel et al, 2016). These discrepancies might be attributable to several differences between the present study and previous studies.…”

“…These areas are not only involved in the processing of dyspnea and other aversive bodily sensations such as pain (Craig, 2002;Tracey & Mantyh, 2007;Van Oudenhove & Aziz, 2013;von Leupoldt et al, 2009), but are also key areas in the processing of negative affectivity such as anxiety (Adolphs, 2013;Etkin, Egner, & Kalisch, 2011;Etkin & Wager, 2007;Sehlmeyer et al, 2009). Notably, activations in these areas are not restricted to the perception of aversive stimuli, but are already present during their anticipation including the expectation of upcoming dyspnea (Faull, Jenkinson, Ezra, & Pattinson, 2016;Grupe & Nitschke, 2013;Holtz, Pan e-Farr e, Wendt, Lotze, & Hamm, 2012;Paulus et al, 2012;Stoeckel, Esser, Gamer, Kalisch et al, 2015;Stoeckel, Esser, Gamer, B€ uchel, & von Leupoldt, 2016).…”

Tools and Resources: Remote, automated and MRI-compatible administration of interoceptive inspiratory resistive loading

“…The previous circuitry that has been employed to manually administer inspiratory resistances within an MRI scanner 16,26,27 is outlined in Figure 1A. In this experimental setup, compressed and humidified medical air was delivered to the participant via a breathing system, whereby air flow was maintained at a rate to adequately allow free breathing and access to an available air reservoir (within a reservoir bag) of 2 L. When a (conditioned) visual cue appeared on the screen, the delivery of compressed air was manually halted via closure of the corresponding air flowmeters, allowing the reservoir bag to empty over the course of approximately 3-8 seconds (anticipation period), followed by the application of inspiratory resistance once the air reservoir was empty.…”

“…We focus on respiration, presenting an advanced circuitry for the automated administration of inspiratory resistances. This circuitry builds on a previously-published magnetic resonance imaging (MRI)-compatible inspiratory resistance circuit 16,26,27 , incorporating computer-controlled solenoid valves for timely commencement and elimination of resistance, and an electronicallycontrolled, flow-mediated inspiratory valve device (POWERbreathe, IMT Technologies Ltd., Birmingham, UK) to allow for adjustable maximal resistances. While the previous methodology has been employed to measure the brain activity (via functional magnetic resonance imaging, or fMRI) related to the conditioned anticipation and perception of inspiratory resistive loads, these advances significantly aid the development of complicated protocols required for a more detailed study of dynamic brain-body interactions 28 .…”

A wider pathological network underlying breathlessness and respiratory failure in amyotrophic lateral sclerosis

“…Observations on breathlessness anxiety in COPD suggest that fear conditioning related to learned negative associations between everyday situations and dyspnoea exacerbate the downward spiral of breathlessness and inactivity. Neuroimaging studies testing this are starting to emerge [22,23], and implicate emotional processes in the medial prefrontal cortex contributing to chronic breathlessness. Whether neurodegeneration in frontal and other emotion-processing brain regions specifically contributes to breathlessness in ALS remains unknown.…”