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Evolution has endowed all humans with a continuum of innate, hard-wired, automatically activated defense behaviors, termed the defense cascade. Arousal is the first step in activating the defense cascade; flight or fight is an active defense response for dealing with threat; freezing is a flight-or-fight response put on hold; tonic immobility and collapsed immobility are responses of last resort to inescapable threat, when active defense responses have failed; and quiescent immobility is a state of quiescence that promotes rest and healing. Each of these defense reactions has a distinctive neural pattern mediated by a common neural pathway: activation and inhibition of particular functional components in the amygdala, hypothalamus, periaqueductal gray, and sympathetic and vagal nuclei. Unlike animals, which generally are able to restore their standard mode of functioning once the danger is past, humans often are not, and they may find themselves locked into the same, recurring pattern of response tied in with the original danger or trauma. Understanding the signature patterns of these innate responses—the particular components that combine to yield the given pattern of defense—is important for developing treatment interventions. Effective interventions aim to activate or deactivate one or more components of the signature neural pattern, thereby producing a shift in the neural pattern and, with it, in mind-body state. The process of shifting the neural pattern is the necessary first step in unlocking the patient’s trauma response, in breaking the cycle of suffering, and in helping the patient to adapt to, and overcome, past trauma.