title: Altered resting state functional connectivity in young survivors of acute lymphoblastic leukemia.
abstract: BACKGROUND
  Chemotherapy treatment for pediatric acute lymphoblastic leukemia (ALL) has been associated with long-term cognitive impairments in some patients. However, the neurobiologic mechanisms underlying these impairments, particularly in young survivors, are not well understood. This study aimed to examine intrinsic functional brain connectivity in pediatric ALL and its relationship with cognitive status.
  
  
  METHODS
  We obtained resting state functional magnetic resonance imaging (rsfMRI) and cognitive testing data from 15 ALL survivors age 8-15 years and 14 matched healthy children. The ALL group had a history of intrathecal chemotherapy treatment but were off-therapy for at least 6 months at the time of enrollment. We used seed-based analyses to compare intrinsic functional brain network connectivity between the groups. We also explored correlations between connectivity and cognitive performance, demographic, medical, and treatment variables.
  
  
  RESULTS
  We demonstrated significantly reduced connectivity between bilateral hippocampus, left inferior occipital, left lingual gyrus, bilateral calcarine sulcus, and right amygdala in the ALL group compared to controls. The ALL group also showed regions of functional hyperconnectivity including right lingual gyrus, precuneus, bilateral superior occipital lobe, and right inferior occipital lobe. Functional hypoconnectivity was associated with reduced cognitive function as well as younger age at diagnosis in the ALL group.
  
  
  CONCLUSIONS
  This is the first study to demonstrate that intrinsic functional brain connectivity is disrupted in pediatric ALL following chemotherapy treatment. These results help explain cognitive dysfunction even when objective test performance is seemingly normal. Children diagnosed at a younger age may show increased vulnerability to altered functional brain connectivity.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California.
authors.forename: Shelli R
authors.initials: SR
authors.lastname: Kesler
authors.forename: Meike
authors.initials: M
authors.lastname: Gugel
authors.forename: Mika
authors.initials: M
authors.lastname: Pritchard-Berman
authors.forename: Clement
authors.initials: C
authors.lastname: Lee
authors.forename: Emily
authors.initials: E
authors.lastname: Kutner
authors.forename: S M Hadi
authors.initials: SM
authors.lastname: Hosseini
authors.forename: Gary
authors.initials: G
authors.lastname: Dahl
authors.forename: Norman
authors.initials: N
authors.lastname: Lacayo
mesh_terms: D000293:Adolescent; D001921:Brain / Q000503:physiopathology*; D002648:Child; D003071:Cognition; D003072:Cognition Disorders / Q000209:etiology / Q000503:physiopathology* / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D009415:Nerve Net / Q000503:physiopathology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000503:physiopathology* / Q000523:psychology / Q000628:therapy; D017741:Survivors
keywords: chemotherapy; cognition; fMRI; leukemia; resting state