Cognition-related connectome gradient dysfunctions of thalamus and basal ganglia in drug-naïve first-episode major depressive disorder

Motivation: The continuous spatial patterns of inter-region connectivity within the subcortical network still remain less well-understood in MDD. Goal(s): Using functional gradient mapping, a novel approach to identify hierarchical organization of functional networks, we aim to evaluate multiscale subcortical gradients in MDD and their association with cognition. Approach: Subcortical gradient alterations at the global-, system-, and subregion-levels and their relation to neuropsychological functioning were assessed in MDD patients relative to healthy controls. Results: Principal gradient values were lower in thalamic and limbic systems but higher in basal ganglia in MDD. Interactions between thalamic and basal ganglia gradient alterations were implicated in MDD-related memory impairments. Impact: Multiscale subcortical gradient alterations can enhance our understanding of MDD-related hierarchical disturbances in subcortical function and may provide useful clinical biomarkers for cognitive impairments in MDD.