Neurochemically informed network control theory reveals energetic dysregulation of altered brain state dynamics in...

Previous studies assessed dynamic functional connectivity in obsessive-compulsive disorder (OCD) by the sliding-window approach, limiting sensitivity to rapid neural fluctuations. Moreover, the mechanisms underlying dynamic transitions between brain states also remain unknown. Therefore, the study aimed to explore the dynamic neural mechanisms of OCD by characterizing state dynamic patterns and the underlying energy basis.

The study recruited 198 OCD patients and 109 healthy controls, characterizing altered state dynamic patterns and underlying control energy in OCD by integrating co-activation pattern (CAP) analysis with network control theory (NCT).

OCD patients showed increased occurrences of the states characterized by ventral attention and somatomotor network co-activation with default mode network suppression (VAN-SMN⁺/DMN^-) and default mode network activation with ventral attention network suppression (DMN⁺/VAN^-), reduced persistence of the actively frontoparietal network with suppressively visual network (FPN⁺/VIS^-) state, and elevated transitions among DMN⁺/VAN^-, VAN-SMN⁺/DMN^-, and SMN-VAN⁺/VIS^- states. Moreover, computational enhancement of FPN⁺/VIS^- state persistence via virtual perturbation partially improved abnormal brain-state dynamics in OCD. NCT further revealed that state transitions from DMN⁺/VAN^- to VAN-SMN⁺/DMN^- or SMN-VAN⁺/VIS^- required reduced control energy under modulation by GABAergic signaling and mitochondrial respiratory capacity, forming a "low-cost pathological shortcut" associated with greater symptom severity; state transitions from SMN-VAN⁺/VIS^- to VAN-SMN⁺/DMN^- were intrinsically energy-demanding, modulated by dopaminergic and serotonergic systems, constituting an "inefficient pathological transition" consistent with repetitive behavior observed clinically.

OCD is characterized by a maladaptive brain-state cycle marked by excessive DMN dominance, frequent shifts to VAN/SMN activation states, and attenuated FPN engagement. Computationally enhancing the persistence of the FPN⁺/VIS^- state via virtual perturbation partially improved the dysregulated cycle in OCD. Within this cycle, two distinct pathological transition modes emerged: a "low-cost shortcut" from DMN to VAN/SMN modulated by GABAergic and an "inefficient transition" from SMN to VAN linked to dopaminergic and serotonergic. These reveal neurochemically grounded alterations in the energy control of abnormal brain-state transitions, offering mechanistic insights into the disrupted neural dynamics of OCD.