Oscillations Governed by the Incoherent Dynamics in Necroptotic Signaling

Emerging evidences have suggested that oscillation is important for the induction of cell death. However, whether and how oscillation behavior is involved and required for necroptosis remain elusive. To address this question, a minimal necroptotic circuit is proposed based on the CNS pathway. Stochastic parameter analysis demonstrates that the essential structure for oscillation of the CNS circuit is constituted by a paradoxical component embedded with positive feedback among the three protein nodes, i.e., RIP1, caspase-8, and RIP3. Distribution characteristics of all parameters in the CNS circuit with stable oscillation are investigated as well, and a unidirectional bias with fast and slow dynamics that are required for high occurrence probability of oscillation is identified. Four types of oscillation behaviors are classified and their robustness is further explored, implying that the fast oscillation behavior is more robust than the slow behavior. In addition, bifurcation analysis and landscape approach are employed to study stochastic dynamics and global stability of the circuit oscillations, revealing the possible switching strategies among different behaviors. Taken together, our study provides a natural and physical bases for understanding the occurrence of oscillations in the necroptotic network, advancing our knowledge of oscillations in regulating the various cell death signaling.

Concurrent EEG- and fMRI-derived functional connectomes exhibit linked dynamics

Connectivity across distributed brain regions commonly measured with functional Magnetic Resonance Imaging (fMRI) exhibits infraslow (<0.1Hz) spatial reconfigurations of potentially critical importance to cognition. Cognitively relevant neural communication, however, employs synchrony at fast speeds. It is unclear how fast oscillation-coupling across the whole-brain connectome relates to connectivity changes in fMRI, an indirect measure of neural activity. In two datasets, electroencephalography (EEG) revealed that synchronization in all canonical oscillation-bands reconfigures at infraslow speeds, coinciding with connectivity changes in concurrently recorded fMRI in corresponding region-pairs. The cross-modal tie of connectivity dynamics was widely distributed across the connectome irrespective of EEG frequency-band. However, the cross-modal tie was strongest in visual to somatomotor connections for slower EEG-bands, and in connections involving the Default Mode Network for faster EEG-bands. The findings provide evidence that functionally relevant neural synchrony in all oscillation-bands slowly reconfigures across the whole-brain connectome, and that fMRI can reliably measure such dynamics.