Recent advances in studying brain-behaviour interactions using functional imaging: The primary startle response pathway and its affective modulation in humans

The startle response is a cross-species conserved defensive reflex that is considered a key tool for cross-species translational research on emotion and cognition. While the neural pathway mediating (affective) startle modulation has been extensively studied in rodents, human work has lagged in the past due to technical challenges. Recent technical advances, however, have finally enabled non-invasive simultaneous EMG-fMRI acquisition and hence opened new avenues for bridging the gap between clinical and basic science.We illustrate key paradigms and methodological tools for startle response assessment in rodents and humans and review evidence for primary and modulatory neural circuits underlying startle responses and their affective modulation in humans. Based on this, we suggest a refined and integrative model for primary and modulatory startle response pathways and conclude that there is strong evidence from human work on the neurobiological pathway underlying the primary startle response while evidence for the modulatory pathway is rather sparse. We suggest that the technical advances allowing for non-invasive simultaneous EMG-fMRI acquisition in combination with the proposed neuro-functional models set the stage for substantially advancing our understanding of the biological mechanisms underlying human emotions and psychopathological conditions - including specific as well as trans-diagnostic mechanisms and cross-species as well as clinical translation. In closing, we summarize detailed methodological considerations to guide future work and provide an outlook on new and exciting research perspectives enabled through the technical and theoretical advances outlined in this work.