Contributions of Amygdala and Striatal Activity in Emotion Regulation Todd A. Hare, Nim Tottenham, Matthew C. Davidson, Gary H. Glover, and B.J. Casey Background: Emotional information can facilitate or interfere with cognitive processes. In this study, we examined the influence of emotional information in biasing performance and the biological basis underlying this influence. Methods: Ten human subjects (five female) were scanned with functional magnetic resonance imaging while performing an emotional go/nogo task. Results: Subjects were slower to approach fearful target expressions and had more difficulty avoiding happy nontarget expressions. The amygdala was recruited most for negative emotional context, and activity in this region was positively correlated with response time when detecting negative expressions. Increased signal in the right caudate nucleus was observed when avoiding nontargets and was negatively correlated with the number of false alarms subjects made. Conclusions: Emotional context can alter behavioral and biological responses when approaching or avoiding a stimulus. We showed that recruitment of the amygdala, a region implicated in evaluating emotional significance, was associated with longer response latencies when approaching negative information, whereas recruitment of the caudate nucleus, a structure previously implicated in reward and impulse control, was most active when avoiding positive information. Our findings have significant implications for exaggerated and inhibited emotional responses that are characteristic of a number of psychiatric disorders. Key Words: Amygdala, striatum, emotion regulation, go/nogo, fMRI E motional values assigned to objects and events play an important role in cognitive processes. Interpretations of objects and events, however, can change as a function of emotional context (Kim et al 2004; Russell and Fehr 1987). The psychologic construct of emotion regulation has been defined as the dynamic influences between emotions and other psychologic or physiologic processes (Campos et al 1994; Cole et al 1994; Fox 1994). As such, emotion regulation is not the simple presence of an emotion like happiness or sadness, but the manner in which an emotion facilitates or interferes with other processes (Cole et al 1994; Frijda 1988). Processes like cognitive or attentional control (Derryberry and Rothbart 1988, 1997; Rothbart and Ahadi 1994; Rothbart et al 1994) and delay of gratification (Mischel 1958, 1961, 1966; Mischel and Metzner 1962; Mischel and Underwood 1974; Toner and Smith 1977; Walls and Smith 1970) can modulate emotional influences and thus play an important role in emotion regulation. The objective of this study was to examine the influence of emotional infor- mation in biasing performance during a go/nogo task and the biological basis underlying this influence. Emotional modulation of cognitive control has been reported as attentional biases to positive and negative information (Der- ryberry 1988; Mogg et al 2000). Behavioral responses are faster or slower in different emotional contexts and vary as a function of subject traits (e.g., negative attention bias in affective disorders; Vasey et al 1996). Attentional bias toward negative or threatening information is hypothesized by some to play a major role in the etiology and maintenance of anxiety and depression (Beck 1967; Bower 1981; Lonigan et al 2004; Mathews and MacLeod 1994; Vasey and MacLeod 2001; Williams et al 1997). This bias in the processing of negative emotional information in affective disor- ders has been assessed through experimental studies examining the behavioral performance of subjects on tasks such as the Emotional Stroop (Williams et al 1996). Studies from our group have found that positive and negative emotional valence can affect cognitive control in normal populations as well (Casey and Tottenham, unpublished data). Neuroimaging and lesion studies (see Phillips et al 2003a) have described neural substrates of affective processing, especially in the amygdala, and demonstrated its influence on behavior (Adolphs et al 1998; Bechara et al 2003). Patients with bilateral lesions of the amygdala are impaired in judging emotional facial expressions and make suboptimal decisions (see Bechara et al 2003). Negatively valenced stimuli in- creased blood oxygen level– dependent (BOLD) signal in the amygdala, and reaction times to negative stimuli were slower compared with neutral stimuli (Monk et al 2003; Simpson et al 2000). Likewise, positively valenced stimuli can also increase activity in regions of the amygdala (Breiter et al 1996; Canli et al 2002; Garavan et al 2001; Killgore and Yurgelun-Todd 2001; Pessoa et al 2002; Somerville et al 2004; Whalen et al 1998b; Yang et al 2002), and happy expressions (positive stimuli) have been found to speed reaction times (Casey and Tottenham, unpublished data) and bias decisions (O’Doherty et al 2003). Thus the amygdala plays an important role in the processing of emotional information, although amygdala ac- tivity and emotional influences can be attenuated by other cognitive processes (Hariri et al 2000). Decreases in amygdala activity are seen when subjects attempt to reduce emotional responses to affective stimuli (Beauregard et al 2001; Levesque et al 2003; Ochsner et al 2002; Schaefer et al 2002). Performing a cognitive task can also reduce the amygdala response to emotional stimuli (Hariri et al 2000, 2003; Monk et al 2003). Understanding the interactions between cognitive and emo- tional processes is important for understanding behavior in both normal and clinical populations. Therefore, the details of these cognitive and emotional interactions have become the focus of an increasing number of studies but at this point remain unclear. From The Sackler Institute (TAH, NT, MCD, BJC), Weill Medical College of Cornell University, New York; Institute of Child Development (NT), Uni- versity of Minnesota, Minneapolis, Minnesota; and Lucas Magnetic Res- onance Imaging Center (GHG), Stanford University, Stanford, California. Address reprint requests to Dr. Todd A. Hare, The Sackler Institute, Weill Medical College of Cornell University, 1300 York Avenue, Box 140, New York, NY 10021; E-mail: toh2003@med.cornell.edu. Received October 6, 2004; revised December 7, 2004; accepted December 28, 2004. BIOL PSYCHIATRY 2005;57:624 – 632 0006-3223/05/$30.00 doi:10.1016/j.biopsych.2004.12.038 © 2005 Society of Biological Psychiatry l