The transformation of groups of previously nonviolent individuals into repetitive killers of defenseless members of society has been a recurring phenomenon throughout history, continuing at the present era. This apparent transition of seemingly normal, “ordinary” individuals, to perpetrators of extreme atrocities is one of the most striking variants of human behavior. This transition is characterized by a set of symptoms and signs for which a common syndrome has been proposed, Syndrome E, as well as a pathophysiological model of a “cognitive fracture” (Fried, Lancet, 1997). A summary of the last two conferences and a survey of the syndrome manifestation in past times and in the current era will be presented.

I will present the main challenges for this third Paris conference on “The Brains that Pull the Triggers”. In this meeting, we have an extraordinary mix of individuals. We have experts who have observed and studied perpetrators of past and present times and have drawn conclusions and formulated models to explain their behavior.

Concurrently we have neuroscientists who have studied complex behavior at the individual and group level from perception to action and from dehumanization to empathy, and have examined the plasticity and fragility of human perception, value representation, decision and action. These biological vulnerabilities are highlighted by the effects of neuroactive drugs in facilitating some of the symptoms and signs of Syndrome E.

The central questions before the conference are:

1. How can we explain the transformation of seemingly ordinary individuals to repetitive perpetrators of extreme violence? Can we begin to formulate a unifying model that will tie the phenomenology of perpetrators with the growing understanding of brain mechanisms of cognitive and affective behavior in individuals and groups.

2. How amenable are the “Brains that Pull the Triggers” to modulation? Are there means of intervention or prevention?