Introduction Breathlessness is the main cause of suffering in COPD. Its brain mechanisms remain poorly understood, yet may represent a novel therapeutic avenue. Until now, functional magnetic resonance imaging (FMRI) studies of breathlessness have been limited to experiments in healthy volunteers. FMRI demonstrates that imagination of painful events engages the same brain networks responsible for perception of physical pain. We adapted this technique to identify brain areas responsible for breathlessness perception in COPD. We hypothesised that healthy controls would demonstrate brain patterns similar to that observed in previous FMRI studies in healthy volunteers. As psychological dysfunction is strongly associated with COPD we hypothesised that patients would show greater engagement of cognitive brain areas.
Methods 44 COPD patients and 40 matched controls undertook FMRI scanning (Siemens 3T), and psychological and physiological assessments. During scanning, participants were presented with previously validated breathlessness-related word cues and rated breathlessness on a visual analogue scale. FMRI analysis was performed with FSL (http://www.fmrib.ox.ac.uk/fsl). Significant activations were determined as Z > 2.3, with a cluster probability threshold of P < 0.05, corrected for multiple comparisons.
A modified shuttle walk test (MSWT) and spirometry were performed. The following questionnaires were administered: Center for Epidemiological Studies Depression Scale, Dyspnoea-12, State and Trait Anxiety Inventory, bespoke catastrophising and vigilance questionnaires, Fatigue Severity Scale and St Georges Respiratory Questionnaire.
Results Imaging and questionnaire results are displayed in the figure. MSWT values (mean ± SD) were 331 +/-193m (patients) and 804 +/-274m (controls) (p < 0.001). FEV1 (% predicted) was 0.6 ± 02(patients) and 1.0 ± 0.2(controls) (p < 0.001)
Conclusions We observed differing brain activation patterns in response to dyspnoea-related word cues between COPD patients and controls. The control group displayed a similar activation pattern to that observed in previous FMRI studies of breathlessness in healthy volunteers while COPD patients display significantly greater activation in the medial prefrontal cortex (emotion control and memory consolidation). Our behavioural data demonstrates greater psychomorbidity in patients. Taking our imaging and behavioural findings together, we propose that in COPD engagement of the medial prefrontal cortex distorts the processing of breathlessness sensations towards greater reliance on fear memories and expectations, contributing to a vicious circle of avoidance and fear.
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