Breathlessness in a virtual world: An experimental paradigm testing how discrepancy between VR visual gradients and pedal resistance during stationary cycling affects breathlessness perception

Introduction The sensation of breathlessness is often attributed to perturbations in cardio-pulmonary physiology, leading to changes in afferent signals. New evidence suggests that these signals are interpreted in the light of prior “expectations”. A misalignment between afferent signals and expectations may underly unexplained breathlessness. Using a novel immersive virtual reality (VR) exercise paradigm, we investigated whether manipulating an individual’s expectation of effort (determined by a virtual hill gradient) may alter their perception of breathlessness, independent from actual effort (the physical effort of cycling). Methods Nineteen healthy volunteers completed a single experimental session where they exercised on a cycle ergometer while wearing a VR headset. We created an immersive virtual cycle ride where participants climbed up 100 m hills with virtual gradients of 4%, 6%, 8%, 10% and 12%. Each virtual hill gradient was completed twice: once with a 4% cycling ergometer resistance and once with a 6% resistance, allowing us to dissociate expected effort (virtual hill gradient) from actual effort (physical effort of pedalling). At the end of each hill, participants reported their perceived breathlessness. Linear mixed effects models were used to examine the independent contribution of actual effort and expected effort to ratings of breathlessness (0-10 scale). Results Expectation of effort (effect estimate ± std. error, 0.63 ± 0.11, p <0.001) and actual effort (0.81 ± 0.21, p <0.001) independently explained subjective ratings of breathlessness, with comparable contributions of 19% and 18%, respectively. Additionally, we found that effort expectation accounted for 6% of participants’ physical effort of pedalling and was a significant, independent predictor (0.09 ± 0.03; p =0.001). Conclusions An individuals’ expectation of effort is equally important for forming perceptions of breathlessness as the actual effort required to cycle. A new VR paradigm enables this to be experimentally studied and could be used to re-align breathlessness and enhance training programmes. ### Competing Interest Statement Dr. Pattinson is named as co-inventor on a provisional U.K. patent application titled ?Use of cerebral nitric oxide donors in the assessment of the extent of brain dysfunction following injury. The remaining authors have no biomedical financial interests or potential conflicts of interest. Drs Pattinson and Finnegan are named as co-inventors on a provisional U.K. patent titled ?Discordant sensory stimulus in VR based exercise" UK Patent office application: 2204698.1 filing date 31/3/2022