Patients with sickle-cell disease exhibit greater functional connectivity and centrality in the locus coeruleus compared to anemic controls

Abstract

HighlightsPatients with sickle-cell disease (SCD) have greater resting-state functional connectivity between the locus coeruleus (LC) and dorsolateral prefrontal cortex (dlPFC).Patients with SCD have greater resting state centrality of the LCSCD patients with chronic pain exhibited even greater functional connectivity between the LC and dlPFC.This study supports hyper-connectivity between the LC and PFC is a potential chronic pain generator.

Functional Connectivity Decreases with Metabolic Stress in Sickle Cell Disease

“…17,24 Additionally, Bhatt et al found differences in connectivity of the locus coeruleus, a region involved in pain processing, in SCD. 23 We also found decreased connectivity within the auditory network, which is supported by mounting evidence that patients with SCD suffer hearing loss. Between 13% and 62% of tested patients are affected by hearing loss, with 6.6% to 13% having a component of sensorineural hearing loss.…”

“…Five additional studies compared fcMRI between controls and adults with SCD. 19,20,[22][23][24] Interpretation and generalization of these investigations is challenging due to small sample sizes, inclusion of all SCD genotypes and/or chronically transfused participants with SCD, and a variety of analytic techniques. Using a graphlasso based test, Coloigner et al did not find connectivity differences in the majority of patients with SCD compared with controls, however, these results are challenging to reconcile with our data as 55% of the SCD cohort in this study was receiving chronic transfusion therapy or had hemoglobin SC disease.…”

“…Using a graphlasso based test, Coloigner et al did not find connectivity differences in the majority of patients with SCD compared with controls, however, these results are challenging to reconcile with our data as 55% of the SCD cohort in this study was receiving chronic transfusion therapy or had hemoglobin SC disease. 20 Bhatt et al reported increased connectivity in the left locus coeruleus and dorsal prefrontal cortex in participants with SCD compared with controls unaffected by SCD using graph theory, 23 and Karafin et al reported regions with both decreased and increased connectivity with the periaqueductal gray in SCD compared with controls. 24 Using independent component analysis, Case et al reported decreased connectivity in the executive control network and increased connectivity in the salience network, 19 whereas Zempsky et al reported decreased connectivity in the salience network in analyses limited to 3 networks.…”

“…The disparate results of prior investigations into the impact of SCD on fcMRI are challenging to interpret due to the heterogeneity in study design and approach. [17][18][19][20][21][22][23][24] We aim to further our understanding of the pathophysiology of the cognitive complications of SCD using robust statistical analyses of fcMRI data, including homotopy (a global metric assessing the connectivity between the left and right hemispheres) 25 and large-scale networks specific to different neurocognitive functions. Using MRI to measure OEF and functional connectivity in a single session, we prospectively enrolled children with SCD and healthy controls to test our hypothesis that children with SCD would have decreased functional connectivity, and that children experiencing the greatest metabolic stress, as measured by OEF, would have disrupted functional network connectivity.…”

“…fcMRI is of additional interest in SCD when considering the possible impact of chronic metabolic stress, as measured by elevated OEF, on the development of the white matter tracks, or structural connectivity, between the cortical regions that encompass these functional networks. The disparate results of prior investigations into the impact of SCD on fcMRI are challenging to interpret due to the heterogeneity in study design and approach 17–24 . We aim to further our understanding of the pathophysiology of the cognitive complications of SCD using robust statistical analyses of fcMRI data, including homotopy (a global metric assessing the connectivity between the left and right hemispheres) 25 and large‐scale networks specific to different neurocognitive functions.…”