Kathleen J. Helton MD, Presenter: Nothing to Disclose

Diana Fridlyand BS, Abstract Co-Author: Nothing to Disclose

Matthew Scoggins PhD, Abstract Co-Author: Nothing to Disclose

Ping Zou PhD, Abstract Co-Author: Nothing to Disclose

Jane Hankins MD, Abstract Co-Author: Nothing to Disclose

Banu Aygun MD, Abstract Co-Author: Nothing to Disclose

Jane Schreiber PhD, Abstract Co-Author: Nothing to Disclose

Robert J. Ogg PhD, Abstract Co-Author: Nothing to Disclose

Children with sickle cell anemia (SCA) are at risk for cognitive impairment, but the etiology of cognitive dysfunction in patients without visible evidence of brain injury remains unknown. We have shown that intelligence quotient in children with SCA is associated with altered blood-oxygenation level dependent (BOLD) functional MRI response to visual stimulation, findings that suggest chronic anemia alters the neural-hemodynamic coupling that supports healthy brain function. We used BOLD fMRI to test the hypothesis that cognitive dysfunction in SCA is associated with altered brain network connectivity.

Following IRB-approval and written informed consent, 15 untreated children (12.37±3.39 years) with SCA underwent fMRI (resting-state and Nback) and neuropsychological testing (IQ, Wechsler Intelligence Scale for Children, 2003). After realignment, slice time correction, spatial normalization and smoothing(SPM8, http://www.fil.ion.ucl.ac.uk/spm/), spatially independent brain regions with correlated temporal patterns of activity (components) were identified with independent component analysis (ICA) of resting and task data (GIFT link?). Adjacency matrices were constructed based on pair-wise correlation of component time courses. Networks metrics (modularity, cost-integrated average degree, cost-integrated average local efficiency, cost-integrated global efficiency) were analyzed in relation to published healthy normal (N) values, age, and IQ.

Global efficiency (SCA=0.4, N=0.6) and modularity (SCA= 0.16, N=0.4-0.6) were lower than normal, and global efficiency was negatively correlated with modularity (p<0.05). Modularity increased and IQ decreased with age, while IQ increased with global efficiency (p<0.05). Connectivity was weakened in typical high level networks, including the default mode network, and frontoparietal networks.

Decline of IQ with age shows adverse affects of disease on cognitive function. Network analysis revealed altered organization of brain networks in children with SCA, and graph-theoretical network metrics reflected abnormal age-related decline in IQ. The connectivity patterns we observed may help to elucidate the mechanism of cognitive dysfunction in SCA

Functional connectivity analysis holds great promise as a clinical adjunct in future studies of patients with SCA to assess effectiveness of treatment in improving neurocognitive function.

Helton, K, Fridlyand, D, Scoggins, M, Zou, P, Hankins, J, Aygun, B, Schreiber, J, Ogg, R, Functional Connectivity in Children with Sickle Cell Anemia and Normal Brain MRI.  Radiological Society of North America 2013 Scientific Assembly and Annual Meeting, December 1 - December 6, 2013 ,Chicago IL. http://archive.rsna.org/2013/13023839.html