Sequential fear generalization and network connectivity in trauma-exposed humans with and without psychopathology

While impaired fear generalization is known to underlie a wide range of psychopathology, the extent to which exposure to trauma by itself results in deficient fear generalization and its neural abnormalities is yet to be studied. Similarly, the neural function of intact fear generalization in people who endured trauma and did not develop significant psychopathology is yet to be characterized. Here, we utilize a generalization fMRI task, and a network connectivity approach to clarify putative behavioral and neural markers of trauma and resilience. The generalization task enables longitudinal assessments of threat discrimination learning. Trauma-exposed participants (TE; N = 62), compared to healthy controls (HC; N = 26), show lower activity reduction in salience network (SN) and right executive control network (RECN) across the two sequential generalization stages, and worse discrimination learning in SN measured by linear deviation scores (LDS). Comparison of resilient, trauma-exposed healthy control participants (TEHC; N=31), trauma exposed individuals presenting with psychopathology (TEPG; N=31), and HC, reveals a resilience signature of network connectivity differences in the RECN during generalization learning measured by LDS. These findings may indicate a trauma exposure phenotype that has the potential to advance the development of innovative treatments by targeting and engaging specific neural dysfunction among trauma-exposed individuals, across different psychopathologies.

Xi Zhu, Benjamin Suarez-Jimenez, Amit Lazarov, Sara Such, Caroline Marohasy, Scott S. Small, Tor D. Wager, Martin A. Lindquist, Shmuel Lissek, Yuval Neria