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Probing the Working Memory System in Chronic Fatigue Syndrome: A Functional Magnetic Resonance Imaging Study Using the n-Back Task

From the Unitat de Psicologia Mèdica, Institut de Neurociències, Universitat Autònoma de Barcelona, Barcelona, Spain (X.C.); the Division of Psychological Medicine and Psychiatry (X.C., D.M.-C., K.A.M., T.C.), the Department of Psychology (D.M.-C., E.L.G.), and the Centre for Neuroimaging Sciences (V.G., M.B., F.Z.), King's College London, Institute of Psychiatry, London, UK.

Address correspondence and reprint requests to Xavier Caseras, PhD, PO Box 69, Division of Psychological Medicine and Psychiatry, King's College London, Institute of Psychiatry, De Crespigny Park Rd., London SE5 8AF, UK. E-mail: x.caseras{at}iop.kcl.ac.uk

Objective: Up to 90% of patients with chronic fatigue syndrome (CFS) report substantial cognitive difficulties. However, objective evidence supporting these claims is inconsistent. The present functional magnetic resonance imaging study examined the neural correlates of working memory in patients with CFS compared with controls.

Methods: Seventeen patients with CFS and 12 healthy control subjects were scanned while performing a parametric version of the n-back task (0-, 1-, 2-, and 3-back).

Results: Both groups performed comparably well and activated the verbal working memory network during all task levels. However, during the 1-back condition, patients with CFS showed greater activation than control subjects in medial prefrontal regions, including the anterior cingulate gyrus. Conversely, on the more challenging conditions, patients with CFS demonstrated reduced activation in dorsolateral prefrontal and parietal cortices. Furthermore, on the 2- and 3-back conditions, patients but not control subjects significantly activated a large cluster in the right inferior/medial temporal cortex. Trend analyses of task load demonstrated statistically significant differences in brain activation between the two groups as the demands of the task increased.

Conclusions: These results suggest that patients with CFS show both quantitative and qualitative differences in activation of the working memory network compared with healthy control subjects. It remains to be determined whether these findings stay stable after successful treatment.

Key Words: chronic fatigue syndrome • n-back • fMRI • working memory

Abbreviations: CFS = chronic fatigue syndrome; fMRI = functional magnetic resonance imaging; PASAT = Paced Auditory Serial Addition Test; WM = working memory; SPECT = single photon emission computed tomography; CDC = Centers for Disease Control and Prevention; BOLD = blood oxygen level dependent; BA = Brodmann's area; TR = repetition time; TE = echo time; SSQratio = sum of squares ratio.