Default-Mode Network Connectivity Changes Correlate with Attention Deficits in ALL Long-Term Survivors Treated with Radio- and/or Chemotherapy

Simple Summary Both chemotherapy and radiotherapy play a role in the neurocognitive impairment of long-term survivors from acute lymphoblastic leukemia, but it is unknown if similar mechanisms are involved. We assessed neurocognitive alterations, brain tissue volumes, and functional connectivity of the main hubs of the default-mode network, in 13 patients treated with chemotherapy and radiotherapy (Group A) and in 13 treated with chemotherapy only (Group B). Correlations with neuropsychological scores, independent of group, were assessed for regions that showed significant differences between the two groups at neuroimaging. Compared to Group B, Group A performed significantly worse at the digit span and digit symbol tests and showed increased functional connectivity between the medial prefrontal cortex and the rolandic operculi, along with the absence of differences in regional brain tissue volumes. Functional connectivity in these regions correlated inversely with speed of processing in both groups, suggesting that similar mechanisms may be involved in the neurocognitive deficits in both groups. Whether chemotherapy (ChT) and radiotherapy (RT) determine neurocognitive impairment in acute lymphoblastic leukemia long-term survivors (ALL LTSs) through similar mechanisms affecting the same brain regions is still unknown. We compared neurocognitive alterations, regional brain tissue volumes (by voxel-based morphometry), and functional connectivity of the main default-mode network hubs (by seed-based analysis of resting state functional MRI data), in 13 ALL LTSs treated with RT and ChT (Group A) and 13 treated with ChT only (Group B). Group A performed significantly worse than Group B at the digit span and digit symbol tests (p = 0.023 and 0.013, respectively). Increased connectivity between the medial prefrontal cortex (the main anterior hub of the default-mode network) and the rolandic operculi was present in Group A compared to Group B, along with the absence of significant differences in regional brain tissue volumes. In these regions, the functional connectivity correlated inversely with the speed of processing scores, independent of treatment group. These results suggest that similar mechanisms may be involved in the neurocognitive deficits in ALL LTS patients, regardless of the treatment group. Further studies are needed to clarify whether these changes represent a direct expression of the mechanisms underlying the cognitive deficits or ineffective compensatory phenomena.