The cortical connectivity of the periaqueductal gray and the conditioned response to the threat of breathlessness.

Olivia K Faull,Kyle Ts Pattinson

doi:10.7554/elife.21749

Abstract

Previously we observed differential activation in individual columns of the periaqueductal grey (PAG) during breathlessness and its conditioned anticipation (Faull et al., 2016b). Here, we have extended this work by determining how the individual columns of the PAG interact with higher cortical centres, both at rest and in the context of breathlessness threat. Activation was observed in ventrolateral PAG (vlPAG) and lateral PAG (lPAG), where activity scaled with breathlessness intensity ratings, revealing a potential interface between sensation and cognition during breathlessness. At rest the lPAG was functionally correlated with cortical sensorimotor areas, conducive to facilitating fight/flight responses, and demonstrated increased synchronicity with the amygdala during breathlessness. The vlPAG showed fronto-limbic correlations at rest, whereas during breathlessness anticipation, reduced functional synchronicity was seen to both lPAG and motor structures, conducive to freezing behaviours. These results move us towards understanding how the PAG might be intricately involved in human responses to threat.

Highlights

Breathlessness is a complex, multi-dimensional sensation that is a major cause of suffering in people with a diverse range of illnesses, including chronic lung disease, cardiac disease and cancer
Task functional magnetic resonance imaging (fMRI) data was analysed for mean changes in Blood Oxygen Level Dependent (BOLD) activity, and functional activity identified in both the ventrolateral PAG (vlPAG) and lateral PAG (lPAG) was subsequently analysed for functional connectivity with the wider cortex both at rest, and during anticipation and breathlessness
We have revealed resting functional connectivity profiles of these active periaqueductal grey (PAG) columns with the wider cortex that align with current theories of threat-induced behaviors, where the lPAG is functionally connected to sensorimotor structures in preparation for fight/flight, whilst the vlPAG is functionally connected to affective and evaluative prefrontal areas

Summary

Introduction

Breathlessness is a complex, multi-dimensional sensation that is a major cause of suffering in people with a diverse range of illnesses, including chronic lung disease (e.g. asthma, chronic obstructive pulmonary disease), cardiac disease and cancer. Subjective perceptions of breathlessness are not a neurological reflection of lung function (Banzett et al, 2000; Teeter and Bleecker, 1998), and can cause crippling anxiety when perceived as a direct threat to survival. These perceptions rely on an intricate system of sensory and affective components within the brain (Hayen et al, 2013b; Herigstad et al, 2011; Lansing et al, 2009), both perceiving ventilatory afferents and evaluating the threat value of these sensations.

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