Psychological Medicine

Original Articles

The neural correlates of fatigue: an exploratory imaginal fatigue provocation study in chronic fatigue syndrome

X. Caserasa1a2 c1, D. Mataix-Colsa2a3, K. A. Rimesa2, V. Giampietroa4, M. Brammera4, F. Zelayaa4, T. Chaldera2 and E. Godfreya3

a1 Unitat de Psicologia Mèdica, Institut de Neurociències, Universitat Autònoma de Barcelona, Catalonia, Spain

a2 Division of Psychological Medicine and Psychiatry, King's College London, Institute of Psychiatry, London, UK

a3 Department of Psychology, King's College London, Institute of Psychiatry, London, UK

a4 Centre for Neuroimaging Sciences, King's College London, Institute of Psychiatry, London, UK


Background Fatigue is the central symptom in chronic fatigue syndrome (CFS) and yet very little is known about its neural correlates. The aim of this study was to explore the functional brain response, using functional magnetic resonance imaging (fMRI), to the imaginal experience of fatigue in CFS patients and controls.

Method We compared the blood oxygen level dependent (BOLD) responses of 12 CFS patients and 11 healthy controls to a novel fatigue provocation procedure designed to mimic real-life situations. A non-fatiguing anxiety-provoking condition was also included to control for the non-specific effects of negative affect.

Results During the provocation of fatigue, CFS patients reported feelings of both fatigue and anxiety and, compared to controls, they showed increased activation in the occipito-parietal cortex, posterior cingulate gyrus and parahippocampal gyrus, and decreased activation in dorsolateral and dorsomedial prefrontal cortices. The reverse pattern of findings was observed during the anxiety-provoking scenarios.

Conclusions The results may suggest that, in CFS patients, the provocation of fatigue is associated with exaggerated emotional responses that patients may have difficulty suppressing. These findings are discussed in relation to the cognitive-behavioural model of CFS.

(Received May 30 2007)

(Revised March 17 2008)

(Accepted March 31 2008)

(Online publication April 30 2008)


c1 Address for correspondence: Dr X. Caseras, PO 69, Section of Cognitive Neuropsychiatry, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK. (Email: