Brain fMRI scan demonstrates that cognitive dysfunction in CFS is due to an energy-inefficient process in the frontal cortex

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Less efficient and costly processes of frontal cortex in childhood chronic fatigue syndrome

Kei Mizunoa, b, , , Masaaki Tanakac, Hiroki C. Tanabed, e, Takako Joudoif, Junko Kawatanif, Yoshihito Shigiharac, Akemi Tomodaf, g, Teruhisa Miikef, h, Kyoko Imai-Matsumurai, Norihiro Sadatod, Yasuyoshi Watanabea, c

Highlights
• Decrease in divided attention was related to fatigue in childhood and adolescence.
• Left frontal cortex of healthy students activated in verbal divided attention task
• Right MFG and ACG were additionally activated in CCFS patients.
• CCFS is characterized as an energy-inefficient process in frontal cortex.

Abstract
The ability to divide one's attention deteriorates in patients with childhood chronic fatigue syndrome (CCFS). We conducted a study using a dual verbal task to assess allocation of attentional resources to two simultaneous activities (picking out vowels and reading for story comprehension) and functional magnetic resonance imaging.

Patients exhibited a much larger area of activation, recruiting additional frontal areas: 1)

The right middle frontal gyrus (MFG), which is included in the dorsolateral prefrontal cortex, of CCFS patients was specifically activated in both the single and dual tasks; this activation level was positively correlated with motivation scores for the tasks and accuracy of story comprehension; and 2) In patients, the dorsal anterior cingulate gyrus (dACC) and left MFG were activated only in the dual task, and activation levels of the dACC and left MFG were positively associated with the motivation and fatigue scores, respectively.

Patients with CCFS exhibited a wider area of activated frontal regions related to attentional resources in order to increase their poorer task performance with massive mental effort. This is likely to be less efficient and costly in terms of energy requirements. It seems to be related to the pathophysiology of patients with CCFS and to cause a vicious cycle of further increases in fatigue.