Resting State Neural Network Properties in Sickle Cell Disease Patients
Authors: Zhang Clara Huishi , Mundahl John , Case Michelle , Datta Yvonne , Nelson Stephen , Gupta Kalpna , He Bin 
Published: November 2019

Abstract
Introduction
One major challenge in the treatment of pain from sickle cell disease (SCD) is the current lack of an objective measure of pain. Therefore, we used functional magnetic imaging (fMRI) to compare a specific brain network in SCD patients with healthy subjects to develop objective methods to assess pain. We hypothesize that in SCD patients, the default-mode-network (DMN) is less active in comparison to healthy subjects. DMN is a prevalent network dynamic that appears in the absence of overt behavior and is thought to be responsible for a host of visceral mental activities. This DMN difference may be due to prolonged SCD-related pain.
Methods
Ten healthy subjects (6 males and 4 females; age: mean=23.3, SD= 3.3 years) and ten SCD patients (5 males, 5 females; age: mean= 28.5, SD=7.1 years) participated in the study following informed consent to the procedures approved by the IRB of the University of Minnesota. Patients were recruited by hematologists at the University of Minnesota Medical Center. None of the patients were experiencing acute crisis during the experiments. FMRI data was acquired with a 3T Siemens Trio whole-body scanner with echo-planar imaging (EPI) sequence. Each fMRI recording lasted about 6minutes. The experiment procedures were well tolerated by all subjects. Both independent component analysis (ICA) and seed-based region of interest (ROI) analysis were applied to the fMRI data, and the analysis was performed using the BrainVoyager QX software.
Results
Experimental and analyticalprocedures were applied to both groups under similar conditions and the recorded data in the two groups have comparable quality. Using the data driven ICA-based analysis, each fMRI data set was decomposed into thirty independent components. The DMN component waseasilyidentified in all of the ten healthy subjects. In contrast, none of the ten SCD patients had any identifiable DMN component in the ICA-based analysis. Seed-based ROI analysis was also performed to find correlational networks. The ROIs were predetermined to be in medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), left and right lateral parietal cortex (LP). Using the time course extracted from the ROIs, DMN was revealed in all ten healthy subjects. However, DMN can only be found in three SCD patients.The identified DMN in patients showed incomplete clusters and had smaller cluster size comparing with the DMNin healthy subjects. By examining different possible ROI locations, DMN identified in patients consistently showed smaller number of voxels compared to controls.
Conclusions
Our findings suggest that the neurological signature of SCD patients may be altered by the chronic painful condition caused by the disease. Diminished activity in the DMN during rest has been previously reported by studies on both cognitive impairments and other types of chronic pain. It is currently unclear whether synchrony among the nodes in the default mode network can be reestablished once the pain condition is alleviated. Knowledge of the neurological characteristics of SCD patients may shed light in understanding in disease and the role of pain in SCD. Changes in DMN activity may also serve as a potential biomarker to quantify pain severity in the future.(This work was supported in part by NIH U01 HL117664 and NSF DGE-1069104.)
References
Baliki, M.N. (2008), ‘Beyond feeling: chronic pain hurts the brain, disrupting the default-mode network dynamics’, The Journal of Neuroscience, vol. 28, no. 6, pp. 1398-1403.
Fox, M.D. (2005), ‘The human brain is intrinsically organized into dynamic, anticorrelated functional networks’,ProcNatlAcadSci USA, vol. 102, pp. 9673–9678.

Disclosures
No relevant conflicts of interest to declare.