Abstract Autism is frequently characterized by hyper-reactivity to emotional and intense stimuli, but also, apparent shutting down or blunted reactions, consistent with hypo-reactivity. This project uses neuroimaging to test a mechanistic model in which the same individuals display hyper-reactivity in brain networks responsible for perceiving emotional and sensory information, but inability to recruit neural mechanisms responsible for physiological and behavioral regulatory responses (i.e., apparent hypo-reactivity). This combination yields inwardly sustained, but outwardly blunted reactions akin to being locked in, “screaming inside” while unable to use typical executive, motor, and social mechanisms to regulate these experiences. N=200 autistic and 100 non-autistic individuals will complete tasks involving hearing criticism and praise, naming the valence of emotional words in alternation with cognitive tasks, and seeing visually intense full-field images as well as resting state assessment. Aims include assessment of early hyper-reactivity in brain systems responsible for perception and emotion generation, and subsequent hypo-connectivity and hypo-reactivity with regions that facilitate regulatory control cognitively, socially, and through motor actions. An integrative mechanistic neural network model will be used to examine whether this formulation could yield individual differences in ecological momentary assessment, ambulatory psychophysiology, and self-reported suicidality in the other projects. The potential significance of this work is to dispel the idea that autistic individuals have blunted reactions, and rather to say that their brains are very reactive, and they cannot effectively express or cope with this reactivity. This formulation could lead to different approaches to intervention than are currently available to the autistic community.