Reduced intrinsic neural timescales and their relationship to global network connectivity in depression

Introduction: Major Depressive Disorder (MDD) is characterized by widespread alterations in brain network organization, but the relationship between temporal dynamics and network connectivity remains poorly understood. We investigated how intrinsic neural timescales (INT), measured through the autocorrelation window (ACW), relate to functional connectivity (FC) in MDD during a disorder-specific task paradigm. Methods: 21 MDD patients, 19 schizophrenia patients (clinical comparison), and 21 healthy controls underwent fMRI scanning during a self-evaluation task. We analyzed temporal dynamics using ACW and examined FC using Network-Based Statistics. The relationship between ACW and FC was assessed using Bayesian modeling. Results: MDD patients showed significantly reduced ACW compared to controls, with the strongest reductions in Control (β = −0.264), Default Mode (β = −0.203), and Somatomotor (β = −0.177) networks. Network-Based Statistics revealed increased FC in MDD (243 unique connections) particularly within Default and Control networks. MDD patients exhibited a disorder-specific inverse relationship between ACW and FC (β = −0.119) that was absent in controls and contrasted with the positive relationship observed in schizophrenia patients (β = 0.189). Discussion: Our findings reveal that MDD involves both temporal dysregulation (shortened neural timescales) and spatial disruption (increased connectivity), with a specific alteration in how these properties are coupled. This suggests that MDD might be understood as involving disrupted integration of temporal and spatial brain dynamics, offering novel perspectives for biomarker development and therapeutic interventions targeting temporal processing abnormalities.