The present study investigated the premise that individual differences in autonomic physiology could be used to specify the nature and consequences of information processing taking place in medial prefrontal regions during cognitive reappraisal of unpleasant pictures. Neural (blood oxygenation level-dependent functional magnetic resonance imaging) and autonomic (electrodermal [EDA], pupil diameter, cardiac acceleration) signals were recorded simultaneously as twenty-six older people (ages 64-66 years) used reappraisal to increase, maintain, or decrease their responses to unpleasant pictures. EDA was higher when increasing and lower when decreasing compared to maintaining. This suggested modulation of emotional arousal by reappraisal. By contrast, pupil diameter and cardiac acceleration were higher when increasing and decreasing compared to maintaining. This suggested modulation of cognitive demand. Importantly, reappraisal-related activation (increase, decrease N maintain) in two medial prefrontal regions (dorsal medial frontal gyrus and dorsal cingulate gyrus) was correlated with greater cardiac acceleration (increase, decrease N maintain) and monotonic changes in EDA (increase N maintain N decrease). These data indicate that these two medial prefrontal regions are involved in the allocation of cognitive resources to regulate unpleasant emotion, and that they modulate emotional arousal in accordance with the regulatory goal. The emotional arousal effects were mediated by the right amygdala. Reappraisal-related activation in a third medial prefrontal region (subgenual anterior cingulate cortex) was not associated with similar patterns of change in any of the autonomic measures, thus highlighting regional specificity in the degree to which cognitive demand is reflected in medial prefrontal activation during reappraisal. © 2009 Elsevier Inc. All rights reserved. Introduction Emotions are intense, short-lived changes in how we feel and in what the brain and body do in response to salient events. They interrupt ongoing behavior and engender the energy we need to make an appropriate behavioral response. Emotions that are too weak or too intense, or whose duration is too short or too long, may not be as effective in serving these functions. Being able to tailor our emotional states, therefore, provides one pathway by which humans avoid illbeing and attain high levels of well-being The ability to tailor our emotional states is known as emotion regulation, which has been defined as "the extrinsic and intrinsic processes responsible for monitoring, evaluating, and modifying emotional reactions, especially their intensive and temporal features, to accomplish one's goals" (Thompson, 1994, p. 27-28). There are many ways of regulating our emotional responses, including situation selection, situation modification, attentional deployment, cognitive change, and response modulation Mostly using functional magnetic resonance imaging (fMRI), neuroimaging studies have implicated lateral ventral, ventromedial, dorsomedial, and dorsolateral regions of prefrontal cortex (PFC) when using reappraisal to decrease