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Brain Advance Access originally published online on June 28, 2008
Brain 2008 131(8):2172-2180; doi:10.1093/brain/awn140
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© The Author (2008). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Increase in prefrontal cortical volume following cognitive behavioural therapy in patients with chronic fatigue syndrome

Floris P. de Lange1, Anda Koers1, Joke S. Kalkman2, Gijs Bleijenberg2, Peter Hagoort1,3, Jos W. M. van der Meer4 and Ivan Toni1,3

1F.C. Donders Centre for Cognitive Neuroimaging, Radboud University Nijmegen, 2Expert Center Chronic Fatigue, Radboud University Nijmegen Medical Center, 3Nijmegen Institute for Cognition and Information, Radboud University Nijmegen and 4Department of General Internal Medicine, Radboud University Nijmegen Medical Center, Netherlands

Correspondence to: Floris P. de Lange, PhD, F.C. Donders Centre for Cognitive Neuroimaging, Radboud University Nijmegen, Kapittelweg 29, 6500 HB Nijmegen, The Netherlands E-mail: florisdelange{at}gmail.com

Chronic fatigue syndrome (CFS) is a disabling disorder, characterized by persistent or relapsing fatigue. Recent studies have detected a decrease in cortical grey matter volume in patients with CFS, but it is unclear whether this cerebral atrophy constitutes a cause or a consequence of the disease. Cognitive behavioural therapy (CBT) is an effective behavioural intervention for CFS, which combines a rehabilitative approach of a graded increase in physical activity with a psychological approach that addresses thoughts and beliefs about CFS which may impair recovery. Here, we test the hypothesis that cerebral atrophy may be a reversible state that can ameliorate with successful CBT. We have quantified cerebral structural changes in 22 CFS patients that underwent CBT and 22 healthy control participants. At baseline, CFS patients had significantly lower grey matter volume than healthy control participants. CBT intervention led to a significant improvement in health status, physical activity and cognitive performance. Crucially, CFS patients showed a significant increase in grey matter volume, localized in the lateral prefrontal cortex. This change in cerebral volume was related to improvements in cognitive speed in the CFS patients. Our findings indicate that the cerebral atrophy associated with CFS is partially reversed after effective CBT. This result provides an example of macroscopic cortical plasticity in the adult human brain, demonstrating a surprisingly dynamic relation between behavioural state and cerebral anatomy. Furthermore, our results reveal a possible neurobiological substrate of psychotherapeutic treatment.

Key Words: neural plasticity; prefrontal cortex; grey matter increase; cognitive behavioural therapy

Abbreviations: CFS, chronic fatigue syndrome; HC, healthy controls; CBT, cognitive behavioural therapy; VBM, voxel-based morphometry; MRI, magnetic resonance imaging; GMV, grey matter volume; SRT, simple reaction time task; CRT, choice reaction time task; WAIS-dst, digit symbol subtest of the Wechsler Adult Intelligence Scale

Received April 8, 2008. Revised June 5, 2008. Accepted June 9, 2008.


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F. P. de Lange, A. Koers, J. S. Kalkman, G. Bleijenberg, P. Hagoort, J. W. M. v. d. Meer, and I. Toni
Reply to: can CBT substantially change grey matter volume in chronic fatigue syndrome?
Brain, August 30, 2008; (2008) awn208v1.
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I. Bramsen
Can CBT substantially change grey matter volume in chronic fatigue syndrome?
Brain, August 29, 2008; (2008) awn207v1.
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