Multiscale connectivity framework for working memory network in paediatric acute lymphoblastic leukaemia survivors

Area of Science:

• Neuroscience
• Medical Imaging
• Cognitive Science

Background:

• Working memory impairments are a common late effect in childhood acute lymphoblastic leukaemia (ALL) survivors.
• The structural network basis of these cognitive difficulties is not well understood, particularly concerning multiscale organization.
• Current connectomic studies often use whole-brain approaches, potentially missing working memory-specific circuitry.

Purpose of the Study:

• To investigate the multiscale structural connectivity of working memory-associated networks in ALL survivors.
• To compare brain network topology between ALL survivors and healthy controls.
• To identify structural changes underlying working memory deficits in ALL survivors.

Main Methods:

• Developed a multiscale structural connectivity framework using diffusion MRI.
• Constructed fine-scale (76-node) and coarse-scale (24-node) structural connectomes.
• Analyzed graph theoretical metrics (clustering, centrality, assortativity, participation) in 70 ALL survivors and 70 controls.

Main Results:

• ALL survivors displayed significant topological shifts in working memory networks compared to controls.
• Increased subcortical clustering and assortativity (caudate, putamen, thalamus) and decreased frontoparietal cortical clustering/assortativity were observed.
• Conversely, subcortical centrality and participation decreased while cortical centrality and participation increased, indicating subcortical segregation and cortical hyperintegration.

Conclusions:

• A broad reorganization of working memory circuitry exists in ALL survivors, characterized by weakened cortical and strengthened subcortical networks.
• These findings highlight potential compensatory mechanisms and provide novel targets for cognitive rehabilitation strategies.
• The multiscale connectomic approach effectively revealed structural alterations in working memory networks relevant to ALL survivors' cognitive outcomes.