Frequent Vaso-occlusive Crises Alter Brain Network Connectivity in Patients with Sickle Cell Disease

Sickle cell disease (SCD) is an inherited hemolytic disorder complicated by acute vaso-occlusive crises (VOCs) that are associated with extremely painful episodes that frequently require hospitalization and opioids for pain control. We previously reported significant correlations between resting state functional connectivity (fs-rc) and number of hospitalizations associated with VOCs (Darbari, 2015). Eight-minute rs-fc and high-resolution T1w structural scans were collected from 22 patients aged 14-73 yrs old. The number of patient-reported pain crises in the preceding 12 months was documented. Data were preprocessed with SPM12 in MATLAB and the Conn toolbox generating seed-to-whole brain functional connectivity maps. First-level analyses correlated seed region time series signal with averaged time signal throughout the whole brain generating bivariate Fisher Z-transformed connectivity maps for each seed from previous findings in fibromyalgia and SCD. Connectivity maps were entered into an SPM regression model with number of VOCs as well as age, sex, and handedness as covariates of no interest. Results were deemed significant with false discovery rate (FDR) p-value<0.05 derived from an uncorrected voxel p-value<0.001. Rs-fc between the dorsal anterior cingulate cortex seed and left dorsolateral prefrontal cortex was negatively correlated with number of VOCs (R=-0.714, PFDR=0.040). There was a significant positive correlation between number of VOCs and rs-fc between the right mid insula seed and the cuneus/precuneus (R=0.737, PFDR=0.046). Management of pain in SCD remains very challenging due to a lack of understanding of the underlying mechanisms. Our results extended the understanding of central mechanisms and VOCs associated brain functional connectivity in SCD.