Task Related Cerebral Blood Flow Changes of Patients with Chronic Fatigue Syndrome: An Arterial Spin Labeling Study

Abstract

Purpose: One hallmark of chronic fatigue syndrome (ME/CFS) is task related worsening of fatigue. Global brain hypoperfusion, abnormal regional activation, and altered functional connectivity of brain areas associated with cognition and memory have been reported but remain controversial.

Methods: We enrolled 17 female participants fulfilling the CDC Criteria for ME/CFS and 16 matched healthy controls (HC). Using a 3T-Phillips Achieva MRI-scanner, pseudo-continuous arterial spin-labeling (pCASL), was used to study the dynamics of regional cerebral blood flow (rCBF) and their relationship to mental fatigue in ME/CFS patients and HC during a demanding cognitive task, i.e. modified Paced-Auditory-Serial-Addition-Testing (PASAT).

Results: ME/CFS subjects reported more fatigue than HC at baseline (p < .01). Global brain perfusion of ME/CFS and HC subjects was similar at rest. The PASAT resulted in significantly increased fatigue in ME/CFS participants and HC. Although not different between groups, overall CBF significantly increased over the first 3 min of the PASAT and then decreased thereafter. Regional CBF (rCBF) changes were significantly different between groups during the post-task recovery period. Whereas improvement of fatigue of ME/CFS subjects was associated with decreased rCBF in both superior temporal gyri (STG), precuneus, and fusiform gyrus, it was associated with increased rCBF in the same areas in HC.

Conclusions: Our results suggest that ME/CFS is associated with normal global CBF at rest and during a strenuous task (PASAT); however rCBF of several brain regions associated with memory, goal-oriented attention, and visual function was differentially associated with recovery from fatigue in ME/CFS patients and HC.

Keywords: Arterial Spin Labeling; Chronic Fatigue; Regional Cerebral Blood Flow.

Conflict of interest statement

Competing interests The authors declare that they have no competing interests.

Figures

Figure 1

Mean (SEM) fatigue ratings by group and segment. Repeated measures ANOVA with time as within and group as between subjects factors revealed a significant quadratic main effect for segment (F(1,29) = 93.09.; p 2p = .76). ME/CFS patients reported greater fatigue than HC (F(1,29) = 13.12; p = .001; η2p = .31). The segment by group interaction effect did not achieve significance (F(1,29) = 2.95, p > .09; η2p = .09).

Figure 2

Mean (SEM) CBF within the a priori mask of fatigue-related regions in ME/CFS patients and HC. A main effect of segment was detected such that the mean rCBF increased from resting baseline to PASAT segment 1 (minutes 0-3), and then declined over the course of the 18-minute ASL scan to baseline levels (F(6,174) = 4.68, p < .0001; η2p = .14). Pairwise comparisons indicated a significant increase in rCBF from baseline to PASAT segment 1 (minutes 0-3) (p = .001). rCBF at PASAT segment 1 was significantly greater than during PASAT segment 3 (minutes 6-9; p = .03), PASAT Segment 4 (minutes 9-12; p = .002), minutes 0-3 of the rest period (p = .002), and minutes 4-6 of the rest period (p = .003). rCBF during PASAT segment 2 (minutes 4-6) was significantly greater than during both rest periods (p < .008), and rCBF during PASAT segment 3 (minutes 6-9) was significantly greater than minutes 0-3 of the rest period (p = .04). rCBF of baseline, PASAT segment 4 (minutes 9-12), and both rest periods did not differ significantly from one another (ps > .22).

Figure 3

Correlation between change in rCBF at right STG and change in fatigue from the beginning to the end of the PASAT in HC (A) and ME/CFS patients (B). For HC, increased blood flow to STG was associated with less fatigue from PASAT performance, while the opposite was true for ME/CFS patients.

Figure 4

Axial views illustrating clusters where decreased blood flow over the course of the 6-minute recovery period was associated with larger reductions in fatigue for ME/CFS patients, but not HC, in A) left fusiform gyrus (−22x, −62y, −7z; 1242 mm3); B) right superior temporal gyrus (61x, −30y, 18z; 216 mm3; 64x, −65y, 13z; 135 mm3) ; and C) left precuneus (−25x, −67y, 38z; 540 mm3).

Figure 5

Correlation between change in rCBF at left precuneus and change in fatigue from the end of the PASAT to the end of the rest period in HC (A) and ME/CFS (B). ME/CFS patients who declined in CBF in left precuneus during recovery showed a greater reduction in fatigue. HC who declined showed a smaller reduction.