Exploring the brain mechanisms of breathlessness through the study of neurological patients

Introduction: There has been a long standing clinical need to offer safer and more efficacious treatment options for individuals with refractory breathlessness. This thesis explores the role of several regions of the brain which have been implicated to have a role in breathlessness perception either from brain imaging studies, or anecdotal evidence from neurological and neurosurgical patients. This thesis explores the neurophysiology of breathlessness with an emphasis on air hunger (AH) in the hope to provide new targets for its symptomatic relief. Methods: Experimentally-induced hypercapnic AH tests, involving raising inspired CO2 and constrained ventilation, were conducted in neurosurgical patients with; (a) thalamic deep brain stimulation (DBS) ON and OFF as treatment for tremor, (b) DBS of the sub thalamic nucleus (STN) ON and OFF as treatment for Parkinson’s disease, and (c) patients with low-grade glioma affecting the insular cortex. Results: Group a (n=16): Thalamic DBS produced significant relief of steady-state AH (p=0.002) with a mean±sd reduction of -14.4±15.5% on a visual analogue scale (VAS), exceeding the minimal clinically important difference of 10% for VAS ratings of AH. Group b (n=18): STN DBS, in contrast, generated a trend towards a heightened AH of 8.7±11.9%VAS in six patients. There was no effect of DBS on lung function or hypercapnic ventilatory response. Group c (n=3): Pre-operatively, AH sensitivities in the patients were strikingly lower compared to 11 healthy controls (2.8±2 versus 11±4%VAS/mmHg; p=0.004). Surgical resection of the glioma had varying effects on AH sensitivity. Conclusion: 1) DBS of closely connected sites activated in previous brain imaging studies of breathlessness have opposing effects on AH sensitivity with a suggestion that thalamic activity modulates AH perception. 2) Insular glioma substantially degrades the ability to perceive breathlessness. The use of Diffuse tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) will help to further decipher network wide effects on AH modulation by neurological stimulation and damage. This thesis provides evidence implicating the thalamus, sub thalamus and insular cortex in the perception of breathlessness while further revealing the neural mechanisms of dyspnoea. These findings propose the possibility of the thalamus, and in particular the insular cortex, to be future targets for non-invasive neuromodulation in the hope to relieve refractory dyspnoea

Grantor dc:publisher

Oxford Brookes University

Author dc:creator

• Chapman, Tom Peter

Contributors dc:contributor

• Moosavi, Shakeeb H.
• Kumar, Sanjay
• Green, Alexander L.

Statement dc:rights

• All rights reserved

Language dc:language

en

DOI dc:identifier

https://doi.org/10.24384/aemj-7696

OAI identifier oai:identifier

tle:92154b85-f12c-4978-95e9-64d857adf8b6:d6bd9758-527a-46cd-bfe2-c433766e8fca:1