FUNCTIONAL NEUROANATOMY OF EMOTION 337 ognition of the expression and that fearful faces are Though this review found that many of the SCC acti- more likely to signify a signal for threat than to induce vations arose from studies in which sadness was tran- fear given that subjects often do not report being ntly induced by autobiographical scripts (George e Hence.th amygdalar ctivati ons may be pri 00 n Derg et al. 9:Liott for proces he ocati ding toother inducti fear faces (Morris et al.1996:Breiter et al.1996 ods The inco istent findings in earlier activation Phillips et al.,1997).aversive pictures (Irwin et al. studies on transient sadness in healthy subjects,par 1996:Taylor et al,1998:Simpson et al,2000),as well ticularly in the subgenual ACC(Gemar et al,1996; as sac et al 1999)and happy faces (Breiter e Pardo et 93:George et al.. 1995,may attrib to the in prov on meth A positi on the fuly all of the with additio task uch as re activated to both pleasant and unpl visualizing emotional memories.Liotti et al.(2000)and Thus,the amygdala may not exclusively respond to Mayberg et al.(1999)attempted to address these per- affectively laden stimuli,but may respond to meaning- ceptua or cogn itive confounds by scanning subjects ul stim general.Ou own findings also concu er they ha eved a de nd. ral amyg the activations in subgenua al.2000e avers BA25). and the arly 70% studies f the Happines structure's role in mediating conditioned r nglia (BG)(F 2A)The cthat this a which enhance information processing to nonaversive may be ir ortant in sitive e otions,such as happi stimuli(Everitt,1991).These findings suggest that the gains support from multiple in vivo investiga- amy ala respond mportanc or stimu tions of addictive substances and behaviors (Breiter et alience egar ence (v e co ent 1997:Stein et al..1998 992:Roch et co 996),rew 999,a with id se(SCR)to affective pictur which der aying a vi n the es (Kocpp to salient arousing stimuli. nd n ive been obs regardless of emotional valence (Lang et al.1993). faces (Whalen et al. 1998a Morris et al 2.2 Sadness and the subcallosal cir ulate Sad oleasant pictures induction was significantly associated with subcallosal et al.,1997a;Lane et al,1999:Davidson and cingulate cortex (SCC)activation. About 46% of sad win,1999), ed recall (George ness in duc lized studies reported nd the Dam region ante P000 a Ci requ any 00 Int olimbic don the basal g or hy has be fou d in ventral striatum is well positioned to res ond to the SCC in resting state studies of patients with clin incentive reward motivation and to pregoal attainment ical depression,a mood disorder with relatively more of positive affect arising from progre on toward a sustained sadness (Baxter et al., 1985:Mayberg,1994 re goal (Dav and 1999 cons Drevets et al As expected,activ ity in he sub gula B 25 nc when o1s8tuali 1999. and th a211005 ulated that d in the BG:60%of s this area may lead those susceptible towards a com- nent of the BG(Fig.2A).Contrary to happ pensatory pattern of hypometabolism. disgust has been theoretically conceptuali as a Reiman and colleagues(1997)found anterior cingulate withdrawal emotion (Davidson et al.1990).The re- activity to rec -genera dD t no -ind ce viewed stu facial y mt rpr ps et taoge he d 07 9 its s (1998)hvpognition of the expression and that fearful faces are more likely to signify a signal for threat than to induce fear given that subjects often do not report being afraid. Hence, the amygdalar activations may be pri￾marily for processing affective information in service of imparting danger warnings. Amygdala activations oc￾cur throughout various evocative stimuli, including fear faces (Morris et al., 1996; Breiter et al., 1996; Phillips et al., 1997), aversive pictures (Irwin et al., 1996; Taylor et al., 1998; Simpson et al., 2000), as well as sad (Blair et al., 1999) and happy faces (Breiter et al., 1996), and positive pictures (Hamann et al., 1999). A positive correlation of blood flow in the amygdala was found with subsequent recall of pleasant pictures (Hamann et al., 1999): in that study, the amygdala activated to both pleasant and unpleasant pictures. Thus, the amygdala may not exclusively respond to affectively laden stimuli, but may respond to meaning￾ful stimuli in general. Our own findings also concur this interpretation since we have observed that amyg￾dala also responds to nonaversive/neutral (Taylor et al., 2000) and positive (Liberzon et al., submitted) pic￾tures, supporting evidence from animal studies of the structure’s role in mediating conditioned responses which enhance information processing to nonaversive stimuli (Everitt, 1991). These findings suggest that the amygdala responds to emotional importance or stimu￾lus salience, regardless of valence (whether the content is pleasant or aversive/unpleasant). This is also consis￾tent with psychophysiologic evidence of skin conduc￾tance response (SCR) to affective pictures which dem￾onstrate a response to salient, arousing stimuli, regardless of emotional valence (Lang et al., 1993). 2.2 Sadness and the subcallosal cingulate. Sadness induction was significantly associated with subcallosal cingulate cortex (SCC) activation. About 46% of sad￾ness induction studies reported activation of the SCC, region localized to the ventral/subgenual anterior cin￾gulate (BA 25), over twice as frequently as any other specific emotion (X2 9.24, P 0.05). Interestingly, hypometabolism or hypoperfusion has been found in the SCC in resting state studies of patients with clin￾ical depression, a mood disorder with relatively more sustained sadness (Baxter et al., 1985; Mayberg, 1994; Drevets et al., 1997). As expected, activity in the sub￾genual cingulate (BA 25) increased when depressed subjects respond to pharmacologic treatment (Brody et al., 1999; Mayberg et al., 2000). George et al. (1995) speculated that dysphoria-induced hyperactivity in this area may lead those susceptible towards a com￾pensatory pattern of hypometabolism. Because Reiman and colleagues (1997) found anterior cingulate activity to recall-generated but not film-induced sad￾ness, they interpreted that the SCC activations may result more from the cognitive process of internally generating emotion, and less from sadness itself. Though this review found that many of the SCC acti￾vations arose from studies in which sadness was tran￾siently induced by autobiographical scripts (George et al., 1995; Lane et al., 1997c; Mayberg et al., 1999; Liotti et al., 2000), the X2 analysis did not support the notion that SCC activation was specifically associated with recall induction, as compared to other induction meth￾ods. The inconsistent findings in earlier activation studies on transient sadness in healthy subjects, par￾ticularly in the subgenual ACC (Gemar et al., 1996; Pardo et al., 1993; George et al., 1995), may be attrib￾uted to the differences in provocation method. Partic￾ularly, subjects were partly or fully scanned while they were actively generating the targeted emotional state with additional cognitive tasks such as recalling or visualizing emotional memories. Liotti et al. (2000) and Mayberg et al. (1999) attempted to address these per￾ceptual or cognitive confounds by scanning subjects after they had achieved a desired intensity of sadness, and confirmed the activations in subgenual ACC (BA 25). 2.3 Happiness and the basal ganglia. Nearly 70% happiness induction studies reported activation in the basal ganglia (BG) (Fig. 2A). The notion that this area may be important in positive emotions, such as happi￾ness, gains support from multiple in vivo investiga￾tions of addictive substances and behaviors (Breiter et al., 1997; Stein et al., 1998; Koob, 1992; Koch et al., 1996), reward processing (Rolls, 1999), and enjoyable (playing a video game) activities (Koepp et al., 1998). Activations in the basal ganglia, including the ventral striatum and putamen, have been observed in response to happy faces (Whalen et al., 1998a; Morris et al., 1996, 1998a; Phillips et al., 1998b), pleasant pictures (Lane et al., 1997a; Lane et al., 1999; Davidson and Irwin, 1999), happiness-induced recall (George et al., 1996b; Damasio et al., 2000), pleasant sexual and suc￾cessful competitive arousal (Rauch et al., 1999; Red￾oute et al., 2000). Given its rich innervation of me￾solimbic dopaminergic neurons, the basal ganglia/ ventral striatum is well positioned to respond to incentive reward motivation and to pregoal attainment of positive affect arising from progression toward a desired goal (Davidson and Irwin, 1999), consistent with the notion that happiness can be conceptualized as an approach emotion (Davidson et al., 1990). 2.4 Disgust and the basal ganglia. Interesting, we also found that disgust induction frequently activated the BG; 60% of studies evoking disgust reported en￾gagement of the BG (Fig. 2A). Contrary to happiness, disgust has been theoretically conceptualized as a withdrawal emotion (Davidson et al., 1990). The re￾viewed studies suggest that, particularly, facial ex￾pressions of disgust activated the BG (Phillips et al., 1997, 1998a; Sprengelmeyer et al., 1998). Sprengel￾meyer and colleagues (1998) hypothesized a specific FUNCTIONAL NEUROANATOMY OF EMOTION 337