Activation of the Medial Prefrontal Cortex and Extended Amygdala by Individual Ratings of Emotional Arousal: A fMRI Study K. Luan Phan, Stephan F. Taylor, Robert C. Welsh, Laura R. Decker, Douglas C. Noll, Thomas E. Nichols, Jennifer C. Britton, and Israel Liberzon Background: Significant differences between individual responses to emotional stimuli can be important for the study of emotion. We investigated whether incorporating individual ratings of emotional arousal in the analysis of functional magnetic resonance imaging (fMRI) data im- proves the detection of activation in the medial prefrontal cortex (MPFC) and sublenticular extended amygdala (SLEA), areas implicated in the processing of emotional salience. Methods: Healthy subjects viewed counterbalanced blocks of aversive, nonaversive, and blank images. Out- side the scanner, they rated the intensity of emotional arousal (salience) of each presented picture. Results: Incorporating the subject’s response to each stimulus by using individualized regressors produced more robust activations within MPFC and SLEA com- pared with a simple boxcar regressor, identical for all subjects. Conclusions: Our findings demonstrate that individual behavioral data are useful in improving detection of activation in block-design functional imaging studies. Biol Psychiatry 2003;53:211–215 © 2003 Society of Bio- logical Psychiatry Key Words: Functional magnetic resonance imaging, medial prefrontal cortex, extended amygdala, arousal, emotion, individual differences Introduction F unctional imaging studies with positron emission to- mography (PET) and magnetic resonance imaging (fMRI) provide an opportunity for in vivo examination of emotional processing in the human brain. Several studies have suggested that the medial prefrontal cortex (MPFC) and the sublenticular extended amygdala (SLEA) respond to the emotional significance of salient stimuli (Breiter et al 1996; Gusnard et al 2001; Hamann et al 1999; Lane et al 1997; Liberzon et al 2000; Morris et al 1997; Phan et al 2001; Simpson et al 2000; Taylor et al 1998; Whalen et al 1998). Although the involvement of these regions in emotional responses has been demonstrated, approxi- mately half of emotion activation studies with similar paradigms do not support these findings (for meta-analy- sis, see Phan et al 2002). One potential contributor to this discrepancy is that many studies fail to account for the effect of individual differences, which can be influential in the evaluation of salience. For example, emotional stimuli are often presented in “blocks,” in which individual trials cluster into “on” periods of activation alternating with “off” control periods. This traditional block design as- sumes that the evoked emotion and brain activation are similar across different subjects; however, emotional re- sponses can vary considerably within and between sub- jects, affected by factors such as the context of presenta- tion, personal experience relating to the emotional content, and the mood of the subject (Lang et al 1998). This design also precludes the examination of brain responses to discrete individual stimuli and is susceptible to potential confounds, such as habituation or anticipation (Zarahn et al 1997). In this fMRI study using pictures from the International Affective Picture System (IAPS; Lang et al 1997), we incorporated individual ratings of emotionally evocative stimuli in the analysis of functional activation data. We used a blocked presentation design to maximize detection power but had subjects rate each picture on arousal, to provide individualized stimuli-specific measures of emo- tional intensity or salience. We hypothesized that incor- porating information about these within- and between- subject differences in emotional ratings would improve the sensitivity for detecting activation in our regions of inter- est—the MPFC and the SLEA. From the Departments of Psychiatry (KLP, SFT, LRD, IL), Radiology (RCW, DCN), Biomedical Engineering (DCN), Biostatistics (TEN), and Neuroscience Program (JCB), University of Michigan; and the Psychiatry Service (IL), Vetererans Administration Medical Center, Ann Arbor, Michigan. Address reprint requests to K. Luan Phan, M.D., University of Michigan, Depart- ment of Psychiatry, UH9D, University Hospital, Box 0118, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0118. Received April 1, 2002; revised June 11, 2002; accepted June 20, 2002. © 2003 Society of Biological Psychiatry 0006-3223/03/$30.00 doi: 10.1016/S0006-3223(02)01485-3