Breathlessness and the brain: the role of expectation.

Purpose Of Review: Breathlessness debilitates countless people with a wide range of common diseases. For some people, the experience of breathlessness is poorly explained by the findings of medical tests. This disparity complicates diagnostic and treatment options and means that disease-modifying treatments do not always have the expected effect upon symptoms.

Opioids for breathlessness: psychological and neural factors influencing response variability.

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Nutritional Ketoacidosis During Incremental Exercise in Healthy Athletes.

Ketosis, achieved through ingestion of ketone esters, may influence endurance exercise capacity by altering substrate metabolism. However, the effects of ketone consumption on acid-base status and subsequent metabolic and respiratory compensations are poorly described. Twelve athletically trained individuals completed an incremental bicycle ergometer exercise test to exhaustion following the consumption of either a ketone ester [-3-hydroxybutyrate--1,3-butanediol] or a taste-matched control drink (bitter flavoured water) in a blinded, cross-over study.

Beyond RPE: The Perception of Exercise Under Normal and Ketotic Conditions.

Aim: Subjective perceptions of exercising exertion are integral to maintaining homeostasis. Traditional methods have utilized scores of 'rating of perceived exertion' (RPE) to quantify these subjective perceptions, and here we aimed to test whether RPE may encompass identifiable localized perceptions from the lungs (breathlessness) and legs (leg discomfort), as well as their corresponding measures of anxiety. We utilized the intervention of ketoacidosis (via consumption of an exogenous ketone ester drink) to independently perturb exercise-related metabolites and humoral signals, thus allowing us to additionally identify the possible contributing physiological signals to each of these perceptions.

The midbrain periaqueductal gray as an integrative and interoceptive neural structure for breathing.

The periaqueductal gray (PAG) plays a critical role in autonomic function and behavioural responses to threatening stimuli. Recent evidence has revealed the PAG's potential involvement in the perception of breathlessness, a highly threatening respiratory symptom. In this review, we outline the current evidence in animals and humans on the role of the PAG in respiratory control and in the perception of breathlessness.

Cortical processing of breathing perceptions in the athletic brain.

Athletes regularly endure large increases in ventilation and accompanying perceptions of breathlessness. Whilst breathing perceptions often correlate poorly with objective measures of lung function in both healthy 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.

On the Metabolism of Exogenous Ketones in Humans.

Currently there is considerable interest in ketone metabolism owing to recently reported benefits of ketosis for human health. Traditionally, ketosis has been achieved by following a high-fat, low-carbohydrate "ketogenic" diet, but adherence to such diets can be difficult. An alternative way to increase blood D-β-hydroxybutyrate (D-βHB) concentrations is ketone drinks, but the metabolic effects of exogenous ketones are relatively unknown.

Breathlessness and the body: Neuroimaging clues for the inferential leap.

Breathlessness debilitates millions of people with chronic illness. Mismatch between breathlessness severity and objective disease markers is common and poorly understood. Traditionally, sensory perception was conceptualised as a stimulus-response relationship, although this cannot explain how conditioned symptoms may occur in the absence of physiological signals from the lungs or airways.

Treating breathlessness the brain: changes in brain activity over a course of pulmonary rehabilitation.

Breathlessness in chronic obstructive pulmonary disease (COPD) is often discordant with airway pathophysiology ("over-perception"). Pulmonary rehabilitation profoundly affects breathlessness, without influencing lung function. Learned associations influence brain mechanisms of sensory perception.

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

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.

Opioid suppression of conditioned anticipatory brain responses to breathlessness.

Opioid painkillers are a promising treatment for chronic breathlessness, but are associated with potentially fatal side effects. In the treatment of breathlessness, their mechanisms of action are unclear. A better understanding might help to identify safer alternatives.

Psychophysical Differences in Ventilatory Awareness and Breathlessness between Athletes and Sedentary Individuals.

Purpose: Breathlessness is a complex set of symptoms that are comprised of both sensory and affective (emotional) dimensions. While ventilation is now understood to be a potential limiter to performance in highly-trained individuals, the contribution of breathlessness-anxiety in those nearing maximal ventilation during intense exercise has not yet been considered as a limiter to performance.

Methods: In this study, we compared the physiology and psychology of breathlessness in 20 endurance athletes with 20 untrained age- and sex-matched sedentary controls.

Conditioned respiratory threat in the subdivisions of the human periaqueductal gray.

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.

Connectivity-based segmentation of the periaqueductal gray matter in human with brainstem optimized diffusion MRI.

The periaqueductal gray matter (PAG) is a midbrain structure, involved in key homeostatic neurobiological functions, such as pain modulation and cardiorespiratory control. Animal research has identified four subdivisional columns that differ in both connectivity and function. Until now these findings have not been replicated in humans.

The effect of acetazolamide on saccadic latency at 3459 meters.

Objective: The effect of altitude on brain function is not yet well understood, nor is the influence of height and speed of ascent. Additionally, the relationship between acute mountain sickness (AMS) symptoms and brain function at altitude is unclear. We hypothesized that a deterioration from baseline measures of brain function occurs after rapid, mechanical ascent to 3459 m and would be less pronounced in persons taking acetazolamide.

Functional subdivision of the human periaqueductal grey in respiratory control using 7 tesla fMRI.

The periaqueductal grey (PAG) is a nucleus within the midbrain, and evidence from animal models has identified its role in many homeostatic systems including respiration. Animal models have also demonstrated a columnar structure that subdivides the PAG into four columns on each side, and these subdivisions have different functions with regard to respiration. In this study we used ultra-high field functional MRI (7 T) to image the brainstem and superior cortical areas at high resolution (1mm(3)voxels), aiming to identify activation within the columns of the PAG associated with respiratory control.

Physiological noise in brainstem FMRI.

The brainstem is directly involved in controlling blood pressure, respiration, sleep/wake cycles, pain modulation, motor, and cardiac output. As such it is of significant basic science and clinical interest. However, the brainstem's location close to major arteries and adjacent pulsatile cerebrospinal fluid filled spaces, means that it is difficult to reliably record functional magnetic resonance imaging (fMRI) data from.