Contrasting resting-state fMRI abnormalities from sickle and non-sickle anemia

Sickle cell disease (SCD) is a chronic blood disorder that is often associated with acute and chronic cerebrovascular complications, including strokes and impaired cognition. Using functional resting state magnetic resonance images, we performed whole-brain analysis of the amplitude of low frequency fluctuations (ALFF), to detect areas of spontaneous blood oxygenation level dependent signal across brain regions. We compared the ALFF of 20 SCD patients to that observed in 19 healthy, age and ethnicity-matched, control subjects. Significant differences were found in several brain regions, including the insula, precuneus, anterior cingulate cortex and medial superior frontal gyrus. To identify the ALFF differences resulting from anemia alone, we also compared the ALFF of SCD patients to that observed in 12 patients having comparable hemoglobin levels but lacking sickle hemoglobin. Increased ALFF in the orbitofrontal cortex and the anterior and posterior cingulate cortex and decreased ALFF in the frontal pole, cerebellum and medial superior frontal gyrus persisted after accounting for the effect of anemia. The presence of white matter hyperintensities was associated with depressed frontal and medial superior frontal gyri activity in the SCD subjects. Decreased ALFF in the frontal lobe was correlated with decreased verbal fluency and cognitive flexibility. These findings may lead to a better understanding of the pathophysiology of SCD.