Faull, O. K. | Search bioRxiv

bioRxiv2018

Opioids for breathlessness: Psychological and neural factors influencing variability in response

Effective management of distressing bodily symptoms (such as pain and breathlessness) is an important clinical goal. However, extensive variability exists in both symptom perception and treatment response. One theory for understanding variability in bodily perception is the Bayesian Brian Hypothesis, whereby symptoms may result from the combination of sensory inputs and prior expectations. In light of this theory, we explored the relationships between opioid responsiveness, behavioural/physiological symptom modulators and brain activity during anticipation of breathlessness. MethodsWe utilised two existing opioid datasets to investigate the relationship between opioid efficacy and physiological/behavioural qualities, employing hierarchical cluster analyses in: 1) a clinical study in chronic obstructive pulmonary disease, and 2) a functional magnetic resonance brain imaging study of breathlessness in healthy volunteers. We also investigated how opioid efficacy relates to anticipatory brain activity using linear regression in the healthy volunteers. ResultsConsistent across both datasets, diminished opioid efficacy was more closely associated with negative affect than with other physiological and behavioural properties. Furthermore, in healthy individuals, brain activity in the anterior cingulate and ventromedial prefrontal cortices during anticipation of breathlessness were inversely correlated with opioid effectiveness. ConclusionDiminished opioid efficacy for relief of breathlessness may be associated with high negative affective qualities, and was correlated with the magnitude of brain activity during anticipation of breathlessness. Clinical implicationsNegative affect and symptom expectations may influence perceptual systems to become less responsive to opioid therapy.

neuroscience↗

bioRxiv2017

Cortical processing of breathlessness in the athletic brain

Athletes regularly endure large increases in ventilation, and accompanying perceptions of breathlessness. While breathing perceptions often correlate poorly with objective measures of lung function in both health and clinical populations, we have previously demonstrated closer matching between subjective breathlessness and changes in ventilation in endurance athletes, suggesting that athletes may be more accurate during respiratory interoception. To better understand the link between exercise and breathlessness, we sought to identify the mechanisms by which the brain processing of respiratory perception might be optimised in athletes. Twenty endurance athletes and 20 sedentary controls underwent 7 Tesla functional magnetic resonance imaging. Inspiratory resistive loading induced conscious breathing perceptions (breathlessness), and a delay-conditioning paradigm was employed to evoke preceding periods of anticipation. Athletes demonstrated anticipatory brain activity that positively correlated with resulting breathing perceptions within key interoceptive areas, such as the thalamus, insula and primary sensorimotor cortices, which was negatively correlated in sedentary controls. Athletes also exhibited greater connectivity between interoceptive attention networks and primary sensorimotor cortex. These functional differences in athletic brains suggest that exercise may optimise processing of respiratory sensations. Future work may probe whether these brain mechanisms are harnessed when exercise is employed to treat breathlessness within chronic respiratory disease.

neuroscience↗