1. 3functional neuroanatomy of emotion_ studies in pet and fmri

8/18/2019 1. 3Functional Neuroanatomy of Emotion_ Studies in PET and FMRI

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i ffer e n ce s i n a c t i va t i on p a t t e r n s fo u n d. U n d e r t h i sircumsta nce, a broader-based meta -a na lysis of multi-le st udies ma y be one solution (Fox et al., 1998). Byxamining fi n d i n gs a c r os s s t u d i es , p a t t e r n s of a c t i va -o n s c a n be e va l u a t e d a c r o s s s i m i l a r a n d d i s s i m i l a r

motional tasks. This meta-analysis examines fi ndingsc r os s i m a g i n g s t u d i es i n s ea r c h of s p ecifi c regionss s o ci a t e d w i t h e m ot i on a l a c t i va t i on i n g en e r a l , w i t h

pecifi c emotions and different induction methods. Wel s o e x a m i n e d i f t h e r e a r e br a i n r e g i o n s a s s o c i a t e di t h e m o t i o n a l a c t i va t i o n t a s ks t h a t h a d a c o g n i t i ve

omponent (e.g. , emotiona l expression recognition,ender discrimination, etc.). Particularly, we examinedow “sensitive” specifi c bra in regions were t o di fferentmotiona l ta sks (refl ected by the percentage of studieseport ing a ctivat ion in a region a ccording to a conditionf interest). We also examined how “specifi c” certainra in regions were for di fferent emotiona l r esponses

refl e c t e d by t h e fr e q u e n c y o f a c t i va t i o n i n a s p e c ifi ce gi on w i t h a g iven t a s k i n com p a r i s on t o o t h er r e -

ions). The effect of gender and valence (the extent toh ich emotion is un plea san t or pleasa nt) on a ctiva tiona t t e r n s , a n d t h e q u e s t i o n o f l a t e r a l i t y i n a c t i va t i o nat terns a re ma jor topics in neuroima ging of emotion,nd th us require an extensive a nd separa te discussion.

Therefore, we have chosen to report these results sep-ra tely (Wa ger et al., in prepa ra tion).

METHODS

Scope of Review

In order to i l luminate both general and specifi c pa t -erns of activation associated with di fferent emotionalasks, we searched peer-reviewed journals (indexed ina r g e d a t a b a s es [M E D L I N E , P s y ch I n f o, B r a i n Ma p ])o r E n g l i s h - l a n g u a g e m a n u s c r i p t s o f P E T a n d fM R Imotion induction studies published between J anuary,990, and December, 2000. To allow us to performedla n n e d m e t a -a n a l y s i s, a l l r e por t s i n cl u d ed m e t t h e

ol low i n g cr i t er i a : (1) Th e y i n vol ved u n m e d ica t e dealthy adults; (2) They focused on higher-order men-

al processes of emotion (thus, studies of lower-orderensory or motor processes, such a s gu sta tory/olfa ctory

r pain induction, were excluded) [see reviews by bym a l l et al., 1999; Casey et al., 1994, respectively]; (3)

They al l measured regional cerebral blood fl ow (e.g.,O 15H 2O-PET) or blood oxygenation (e.g., BOLD-fMRI)

c r os s t h e e n t ir e br a i n (i .e ., e xcl u d in g s t u d i es t h a tocused on l imited regions of the brain); (4) They al lsed th e image subtra ction methodology t o determinectivation foci ; (5) They provided standard TalairachTa laira ch an d Tournoux, 1988) or Montr eal Neuro-ogic Inst itut e (MNI) coordina tes, a llow ing for compa r-son of fi ndings across di fferent studies and differentaborat ories. We chose not to include studies on a ver-ive and trace conditioning (Bü chel et al., 1998; Morris

et al. , 1998b; LaBar et al. , 1998; Bü chel et al. , 1999)

beca u s e t h o se t a s ks i n vol ve a s s o ci a t i ve l e a r n i n g a n d

behavioral conditioning (including acquisition and ex-

t i n ct i on ), r e n d er i n g t h e m i n com p a r a ble t o t h e e m o-

t i on a l t a s ks i n o ur d a t a ba s e. F u r t h e r m or e , t h e s e fe a r -

con d it i on in g r el a t ed a c t iv a t i on s w e r e ex t en s iv el y

d is cu s sed i n a r ecen t r ev iew b y B ü c h e l a n d D o l a n

(2000). Only activation peaks were examined in this

m e t a -a n a l y s is . Th e r e por t i n g of d ea c t i va t i on or d e -cr ea s e s i n b r a i n a c t iv it y w a s n ot con s is t en t a c r os s

studies which did not a l low meaningful genera l iza tion.Also, the neural mechanisms underlying reported de-

activations remain undetermined and their interpreta-

tions rema in inconclusive or u nclea r (Hut chinson et al.,1999; Raichle et al., 2001).

Organization of Results

Fifty-fi ve publications/studies (43 P ET a nd 12 fMRI)spanning from May, 1993, to December, 2000, that met

our da ta base criteria , yielding 119 subtra ctions/contr a stsand 761 individual activation peaks, were included for

meta -a na lysis (Ta ble 1). B eca use th e stud ies a dopted dif-

ferent a na lysis methods and signifi cance criteria, a ll fociwere accepted when reported as signifi cant by the crite-ria designated in the individual studies.

The activation r esults ar e grouped in the following

manner: (1) Regions associated with Individual Emotion

(fear, sa dness, disgust, a nger, ha ppiness); (2) regions a s-

sociated with Induction Method (visual, auditory, auto-

biogra phica l reca ll/ima gery); a nd (3) regions a ssocia ted

w ith presence a nd a bsence of Cognitive Dema nd. Ta ble 1lists all studies included in the review, arranged alpha-

betically, and identifi es the Individual Emotion exam-ined and the Induction Method employed. We examined

the effect of Cognitive Demand, as a separate but related

component of In duction Meth od, for a va riety of rea sons.

Neuroimaging literat ure often distinguishes betw een

cognitive and emotional tasks, but the majori ty of the

emotional tasks contain various degrees of cognitive de-

mand. Furthermore, there is a clear interaction between

emotion and cognition on a functional level. To examine

th e neuroa na tomic ba sis of this intera ction, w e exam ined

the effect of these cognitive components in emotion acti-va tion by grouping conditions in wh ich a n emotiona l ta sk

was coupled with a concurrent cognitive task (e.g., gen-

der/emotional expression discrimina tion, emotional ra t-

ing, pictu re/fa ce recognit ion/encoding, n a min g, coun tin g,a ut obiogra phical recall/ima gery, etc.) a s E motion Cog-

nition or w i t h C o gn it i ve D e ma n d . C on ver s ely , w e

grouped conditions in which the emotional task did not

explicitly have a cognitive component (i.e., passive view-

ing, passive listening) as Emotion alone or w i t hout Cog-

nitive Demand. This classifi cation allows us to examinethe effect of a “nonemotional” cognitive component onemotiona l ta sks.

32 P H AN E T AL .


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Th e s t a n d a r d coor d in a t e s of a c t iv a t i on p ea k s r e-orted by individual studies were plotted onto lateralnd medial views of a 3-D ca nonica l bra in image (SP M

96, Wellcome Department of Cognitive Neurology, Lon-d o n ; d e r i ve d fr o m t h e M N I br a i n t e m p l a t e ) . F i g u r e s1A–1C s h ow t h e r es u lt of g r ou pi ng p lot t e d a c t iv a -

TABLE 1

List of E motion Activat ion St udies Included in the Meta-Ana lysis

t u dy No. R efer ence

I n duct ion Met h od Type of E m ot ion

Visua l Audit ory R eca ll H a ppy F ea r Anger S a d D isgu st

1 B a ker 97 X X X

2 B ea ur ega rd 97 X

3 B ea ur ega rd 98 X X4 B la ir 99 X X X

5 B lood 99 X

6 B r eit er 96 X X X

7 C a nli 98 X

8 C r osson 99 X

9 D a ma sio 00 X X X X X

10 D ola n 00 X

11 D ougher t y 99 X X

12 Frey 00 X

13 G em a r 96 X X

14 G eorge 93 X

15 G eorge 94 X X

16 G eorge 95 X X X

17 G eorge 96a X

18 G eorge 96b X X X

19 H a m a nn 99 X

20 H a r ir i 00 X

21 I senber g 99 X X

22 K im br ell 99 X X X

23 K ossly n 96 X

24 L a n e 97a X

25 L a n e 97b X

26 L a n e 97c X X X X X

27 L a n e 98 X X

28 L a n e 99 X

29 L iber zon 00 X

30 L iot t i 00 X X X

31 Ma ddock 97 X X

32 Ma yberg 99 X X33 Morr is 96 X X X

34 Morr is 98a X X X

35 Morr is 99 X X

36 Na ka m ur a 99 X

37 P a r a diso 97 X X X X

38 P a r a diso 99 X

39 P a r do 93 X X

40 P a r t iot 95 X X

41 P hillips 97 X X X

42 P hillips 98a X X X X

43 P hillips 98b X X X

44 P iet r in i 00 X

45 Ra uch 99 X

46 Redou t e 00 X47 Reim a n 97 X X

48 Roy et 00 X X

49 S h in 00 X

50 S im pson 00 X

51 S prengelm ey er 98 X X X X

52 Ta y lor 98 X

53 Ta y lor 00 X

54 Tea sda le 99 X

55 Wh a len 98b X

333FU NCTIONAL NE UR OANATOMY OF EMOTION


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FIG. 1A. Activation foci: Individua l emotion.

FIG. 1B. Activation foci: Induction method.

34 P H AN E T AL .


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on foci a ccording to I ndividual Em otion, InductionM et h o d , a n d C og n i t ive D e m a n d . I n or d e r t o m a ke d i -

ect com pa r i s on s a c r os s s t u d ies , w e t r a n s l a t e d r e-ort ed Ta lair a ch coordina tes (Ta laira ch an d Tournoux,998) int o MNI coordina tes (tr a nsforma tion developedy Ma tt hew B rett , ht tp://w w w .mrc.cbu.cam.a c.uk/Im-ging). Because differences in image smoothing tech-iques can lead to different numbers of activation foci,e ch os e n o t t o i n c lu d e s p a t i a l e x t e n t of a c t i va t i oneaks wh en plott ing onto the 3-D ca nonica l bra in.

For a semiqua nti ta t ive a na lysis, we divided the at lasrain into 20 general regions, and examined whetherctivations in each specifi c region was associated withifferent Individual Emotion, Induction Method, and

ognitive Deman d. Ea ch study included in t his review dentifi e d t h e l o c a t i o n o f t h e a c t i va t i o n p e a k a s a n a -o m ica l s t r u ct u r e /g y r u s a n d /or B r od m a n n a r e a . Wesed this informa tion to loca lize th e activa tion pea ks in

h e 20 bra in regions used in t his review. The num ber ofctiva tion pea ks r eported for a s ingle region differedccording to each study ’s chosen stat ist ical thresholdnd analysis methods. Therefore, we considered a re-ion as activated for a particular study i f one or morec t i va t i on p ea k i n t h i s r e g ion w a s r e por t e d . Th i s a p -roa ch w a s chosen t o counterba lance the tendency forve r e s t i m a t i n g a c t i va t i o n s ba s e d o n va r i a bl e t h r e s h -lds used in di fferent studies, and al lowed us to esti-

m a t e t h e p e r c e n t a g e o f s t u d i e s t h a t r e p o r t e d a n a c t i -va t i on foci i n a s p ecifi c r e gi on i n r e sp on s e t o e a ch

Individual Emotion, Induction Method, and CognitiveDema nd (Figs. 2A–2C).

Additionally, we examined how specifi c the reportedr e g i o n a l a c t i va t i o n s w e r e t o I n d i vi d u a l E m o t i o n , I n -duction Method, and Cognitive Demand. For al l s tud-i e s t h a t e m p l o y e d s i m i l a r c o n t r a s t s a n d m e t h o d s , w ecompared the number of s tudies that found activationi n a p a r t i cu l a r r e gi on t o t h o s e t h a t d i d n ot u s in g c h i-squa re (X 2) analysis. The results of the X 2 a n a l y si s a r epresented in Fig. 2.

RESULTS AND DISCUSSION

1. R egions I nvolved A cross I n di vidu al E m ot ions

1.1. General emot ional processin g and t he m edi al

prefrontal cortex. No specifi c brain region was consis-tently a ctiva ted in t he ma jority of s tudies, across indi-vi du a l e m ot i on s a n d i n d u ct i on m e t h od s , s u g g es t i n gthat no single brain region is commonly activated by allemotional tasks. Although no region was activated inover 50% of a l l s t udies, we did fi n d t h a t t h e m e d i a lp r efr on t a l cor t e x (M P F C ) w a s com m on l y a c t i va t e d ,a n d t h a t i t s a c t i v a t i o n w a s n o t s p e c ifi c t o a s pecifi cemotion or induction method (see Figs. 2A and 2B).

FIG. 1C. Activation foci: Cognitive demand.



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While there may not be a particular brain region thats absolutely necessary for all emotional functions, theom m on a ct i va t i on o f t h e M P F C m a y r efl e ct t h a t ce r -ain aspects may be shared across di fferent emotionala s k s . F ig u r e 2A s how s t h a t t h e M P F C w a s a ct i va t e dcross multiple individua l emotions (four of fi ve spe-ifi c emotions in at least 40%of studies). Accordingly,

X2 a n a l y s i s r e ve a l e d n o s p e c ifi c association between

h e M P F C a n d I n d iv id u a l E m ot i on a s com pa r e d t other regions. These fi n d in g s s u gg es t t h a t t h e M P F C

m a y h a ve a g e n e r a l r o l e i n e m o t i o n a l p r o c e s s i n g , a su g g e s t e d by L a n e , R e i m a n , a n d c o l l e a g u e s , w h o r e -or t e d t h a t e m ot i on a l fi l m s , p i c t u r e s , a n d r e c a l l a sells as positive and negative emotion, happiness, sad-e s s , d i s g u s t , a n d t h e m i x t u r e o f t h e s e e m o t i o n s a l lep a r a t e ly en g a g ed t h e M P F C (L a n e et al. , 1997a;a n e et al., 1997c; Reiman et al., 1997). This is consis-

e n t w i t h t h e n o t i o n t h a t a n u m be r o f p r o c e s s e s a r eotential ly common to various emotional tasks (e.g. ,ppra isal/evalua tion of emotion, emotiona l regula tion,

nd emotion-driven decision-ma king). La ne et a l .1997b) did fi n d t h a t t h e M P F C ( B A9) a c t i va t e d w h e nubjects internally-attended to their emotional state,ut not when they externally at tended to nonaffectiveha ra cterist ics of a picture st imulus. Furth ermore, a c-vi t y i n t h e M P F C h a s be e n s h o w n t o c o r r e l a t e w i t hmotiona l aw a reness to both fi lm and recall-generatedmotion, sug gesting it s role in detecting emotional sig-a ls from both exteroceptive a nd interoceptive cuesLane et a l ., 1998). One possibility t herefore is tha t th e

MPFC may be involved in the cognitive aspects (e.g. ,t t ention to emotion, a ppraisal/identifi cation of emo-

on) of emotiona l processing (Drevets an d Ra ichle,998).

Given the putative importance of cognition in emo-on , w e q u e s t ion e d w h e t h e r t h e M P F C ca n be s u bdi -ided into affective and cognitive regions, which haseen observed in the anterior cingulate cortex (ACC)Bush et al., 2000). The ACC is kn own to be in volved inform of at tention that serves to regulate both cogni-ve and emotional processing (Whalen et al. , 1998a;u s h et al., 2000), a nd is closely int erconnected t o th e

M P F C ( P e t r i d e s a n d P a n d y a , 1 9 9 9 ; D e vi n s ky et al . ,995). F i g u r es 1A a n d 1B s h ow t h a t a c t i va t i on s r e -

orted in the prefrontal cortex in response to differentn d i vid u a l E m o t i on s a n d I n d u ct i on M et h o d s a r e l o-ated w ithin ventra l-rostra l BA 9 a nd 10 of MPF C, a ndx t e n d i n t o t h e a f fe c t i ve d i vi s i o n o f r o s t r a l a n t e r i o ringula te cort ex (ACC a d) (B A rostra l 24, a nt erior/ven-r a l 32, 33). While the a ctivat ions loca ted in t he a rea ofhe MP FC a re more ventr a l and less dorsa l , we did notnd a ny evidence for a functiona l a ffective-cognitiveivision of the MP FC. Our C ognitive Demand an a lysise ve a l ed t h a t r e la t i ve ly m u ch few e r E m o t i on a l on e eaks fell into dorsal MPFC (see Fig. 1C), in compari-o n t o s t u d i e s w i t h t a s ks t h a t i n vo l ve d E m o t i o n a n d

C ognit ion. T h u s , M P F C a p p e a r s e q u a l l y s e n s i t i ve t o

bot h e m ot i on a l t a s ks w i t h a n d w i t h o u t C o g n it i ve D e -m a n d , a s a c t i va t i o n s fr o m bo t h c o n d i t i o n s c l u s t e r i nven t r a l M P F C (s ee F i g s . 1 C a n d 2C ). I n t e r es t i n g ly ,previous meta-analyses of cognition revealed that ther o s t r a l - v e n t r a l a n d o r b i t a l r e g i o n s o f t h e M P F C a r el a r g el y i n sen s it i ve t o cog n it i ve t a s k s (D u n ca n a n dOwen, 2000; Cabeza and Nyberg, 2000).

2. R egions A ssociat ed w i t h I ndi vidu al E m ot ions

2.1 Fear and t he amygdala. Specifi cally, fea r induc-t i on h a d a s t r o n g a s s oci a t i on w i t h t h e a m y g d a l a . S i xt yp er cen t of s t u d ies t h a t ex a m in ed f ea r a c t iv a t e d t h ea m y g d a l a (X 2 12.57, P 0.01) (Fig. 2A). Severall ines of evidence support the n otion tha t the a mygda lais responsible for detecting, generat ing, an d ma inta in-i n g fea r -r e la t e d e m ot i on s . P a r t i cu l a r l y , t h e a m y g d a l aha s been implica ted in the recognition of fea rful fa cialexpressions (Adolphs et al., 1995; Calder et al., 1996),feelings of fear after procaine induction (Ketter et al.,

1996), fear conditioning (LeDoux, 1993; Bechara et al.,1995; La B a r et al., 1995; Morr is et al., 1998b; Wha len etal. , 1998b), and in evocation of fearful emotional re-sponses from direct stimulation (Halgren et al., 1978).The am ygda la a lso a ppea rs importa nt in the detectionof environment threat (Scott et al. , 1997; Isenberg etal. , 1999; P hillips et al. , 1 9 9 8 a ) , a s w e l l a s i n t h ecoor d i n a t i on of a p p r op r ia t e r e sp on s es t o t h r e a t a n dd a n g e r (K l u ber a n d B u cy , 1939; We is kr a n t z , 1956;King, 1992). Strikingly, of the eight studies that exam-ined cerebral responses t o fearful faces, s ix pointed t othe cri t ical involvement of th e a mygda la (Morris et al.,

1996; Breiter et al., 1996; Phillips et al., 1997; Phillipset al., 1998a ; Morris et al., 1998a; Wha len et al., 1998a).F e a r - a s s o c i a t e d a m y g d a l a r a c t i va t i o n s a l s o e x t e n d e di n t o o t h e r m o d a l i t i e s s u c h a s w o r d s ( I s e n be r g et al. ,1999) a nd voca lizat ions (P hillips 1998a ). Morris et al.( 1 9 9 6 ) fo u n d t h a t t h e a m y g d a l a r r e s p o n s e t o fe a r fu lfaces showed a signifi c a n t i n t e r a c t i o n w i t h t h e i n t e n -sity of emotion (increasing with increasing fearfulness)a n d t h a t t h e a c t i v a t i o n w a s n o t c o n t i n g e n t u p o n t h eexplici t processing of facial expression, a s subjectswere instructed to classi fy emotional faces by gendern ot b y e mot i on . S u ch a n i n t er p r et a t i on i s f u r t h er

s t r e n g t h en e d by fi n d i n g s fr o m s t u d i e s u s i n g m a s ke dfearful faces which found that the amygdalar responseoccu r r e d e ve n w h e n t h e fea r fu l e x pr e ss ion w a s n otconsciously perceived or even when subjects did notexperience fear subjectively (Morris et a l . , 1998b;Whalen et al., 1998a ).

G i ven t h a t fea r i s t h e m os t s a l ie n t o f t h e i n d ivi du a le m ot i on s , a n a l t e r n a t i ve in t e r p r et a t i on for t h e a m y g -d a l a ’s involvement is tha t it ha s a more general role forvigi lance or for processing sal ience, or at tr ibutes thatmake st imuli meaningful (Davis and Whalen, 2001).Whalen et al. (1998b) observed that the amygdala re-sponds to fearful faces despite the lack of explicit rec-

36 P H AN E T AL .


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FIG. 2A. Regional activations: Individual emotions.

38 P H AN E T AL .


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FIG. 2B. Regional activations: Induction method.



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unctiona l role for the ba sal gan glia in processing d is-u s t , c o n s i s t e n t w i t h o bs e r va t i o n s t h a t p a t i e n t s w i t h

Hu n t i n g t o n’s disease and obsessive-compulsive disor-e r , w h o h a ve n e u r o p a t h o l o g y i n t h e i r ba s a l g a n g l i a ,a ve impairment s in recognizing fa cial expressions ofisgust compared to other emotions. The activationse e n i n t h e ba s a l g a n g l i a i n r e s p o n s e t o d i s g u s t m a yepresent a state of preparedness tr iggered by a warn-

ng stimu lus to process emotiona lly salient informa tionSprengelmeyer et al. , 1998). With i ts known motoru n ct i on s , t h e ba s a l g a n g l i a m a y a l s o s er ve t o coor d i -a t e a p pr op r ia t e a ct i on r e sp on s es t o s t i m u l i t h a t u n -leasant (inducing disgusting), or pleasing (promotinga ppiness), in nat ure, and guide the orga nism towa rdsd es i r ed g oa l (e .g . , t o a p pr oa c h or w i t h d r a w ) (P a n k-

epp, 1998).

. Regions Associ ated wi th I nd uction M eth od

3. 1 R egions involved in emot ion induct ion w it h and

w it hout cognit ive demand. This meta -a na lysis foundhat emotional tasks with cognitive components specif-ca l l y e n ga g e d t h e AC C a s com p a r e d t o p a s s ive e m o-ona l condit ions (36 vs 12%, r espectiv ely; X 2 3.52,

P 0.06). Earlier, when discussing the fi ndings of theM P F C a c t i va t i on w i t h bo t h E m ot i on Cognition and

m otion alone ta sks, we hypothesized tha t a ctiva tionseen in the MPFC are driven by the general componentf the emotional task (e.g. , with l i t t le impact by Cog-i t i ve D e m a n d ) , a n d i n t e r p r e t e d t h a t t h e M P F C m a yave a general role in emotional processing. We spec-l a t e d t h a t t h e M P F C m a y r e s p o n d t o c o g n i t i v e a s -

ects tha t a re potentia l ly common a cross va rious emo-onal responses (e.g. , at tention to emotion, appraisalr interpretation of emotion), which are implicit to themotional tasks and therefore are present both in thetudies with Cognitive Dema nd a nd in the studies withm otion alone. However, based on t his an a lysis , wh en

he cognitive components ar e explici t to a n emotiona lask (e.g. , gender identifi cat ion, recognition/encodingr rat ing of emotional st imuli , biographical recal l ofm ot i on ) r e n d er i n g t h e s e t a s k i n t h e “with Cognitivee m a n d” ca t e gor y , i t a p pea r s t h a t t h e A C C is r e-

r u i t e d . T h e r e fo r e , t h e AC C a d m a y i n t e r a c t w i t h t h e

MPFC to regulate interconnected cognitive and emo-ona l ta sks, depending on wh ether t he cognitive com-on e n t i s i m pl ici t or e xp li ci t t o t h a t e m ot i on a l r e -p o n s e . T o g e t h e r , t h e r o s t r a l AC C a n d M P F C , w i t hxtensive connections to subcortical limbic structures,onstitute both the heteromodal association cortex andaralimbic cortex respectively, and therefore comprise

p la u s i ble t r a n s it i on a n d i n t er a ct i on z on e be t w e enffective and cognitive processing.

T h e M P F C a n d A C C a d m a y a l s o h a v e a d d i t i o n a lmotiona l m odula tory functions from t his cognitive-motion interaction. As noted above, conditions withn d w i t h o u t C o g n i t i v e D e m a n d e q u a l l y a c t i v a t e t h e

MP FC , w hile cognitively-bound emotiona l ta sks specif-ical ly engaged ACC. While most Individual Emotions

a c t i va t e bo t h t h e M P F C a n d AC C , o n e e x c e p t i o n i n -volves fear , which recruits this region at frequenciesfewer tha n 30% a nd 20% respectively (see Fig. 2B).

I n s t ea d , f ea r s t u d ie s e n g a g e t h e a m y g d a l a r ob u st l y(over 60% frequency; discussed ear lier). Additiona lly,

p a s s ive e m ot i on a l con d i t ion s w i t h o u t C o gn i t ive D e -

ma nd (e.g. , Em otion alone) a ctiva te the amygda la moreoften than cognitive emotional tasks. Given their pu-

tative affective-cognitive functions and reciprocal con-n e c t i o n s t o s u bc o r t i c a l l i m bi c s t r u c t u r e s , t h e M P F C

a n d AC C c o u l d s e r ve a s t o p - d o w n m o d u l a t o r s o f i n -tense emotional responses, especially those generatedby t h e a m y g d a l a . Se ver a l l in e s o f e vi d en ce s u pp or t

s uch a n in t er pr et a t i on . F r om a n i ma l s t ud ies , t h ea m y g d a l a h a s be en s h ow n t o be c r it i ca l i n fe a r con d i -

tioning (LeDoux, 1994). However, one can prolong thee x t i n c t i o n o f t h i s c o n d i t i o n e d fe a r by a bl a t i o n o f t h eM P F C ( M o r g a n et al. , 1993). Lesions in the human

r o s t r a l M P F C a l s o l e a d t o s o c i a l l y i n a p p r o p r i a t e e x -pressions of emotions and impairments in making ad-

va n t a g e ou s p er s on a l l y r e le va n t d e ci s ion s (D a m a s i o,1994), sugg estin g a la ck of cognit ive processing of emo-tionally “loaded” s i tua tions. Furt hermore, glucose me-tabolism in the MPFC is strongly inversely associated

with the glucose metabolic rate of the amygdala (Am-bercrombie et al. , 1996). O u r g r ou p h a s fou n d t h a ta c t i vi t y i s t h e a m y g d a l o i d r e g i o n i s a t t e n u a t e d w h i l e

t h e M P F C a n d c in g u la t e s u lcu s a r e a c t i va t e d d u r in g acognitive appraisal condition of aversive visual stimuli

(versus passive viewing) (Taylor et al., submit ted). Ad-d i t ion a l ly , d e a c t i va t i on of t h e a m y g d a l a h a s bee n o b-s e r ve d i n s e ve r a l t a s ks t h a t i n vo l ve h i g h e r c o g n i t i veprocessing (Drevets and Raichle, 1998). One al terna-tive hypothesis of these reciprocal fi ndings is that l im-bi c s t r u c t u r e s , l i ke t h e a m y g d a l a , a r e m o r e l i ke l y t or e s p o n d t o s t i m u l i t h a t a r e m o r e “emotive” a t a s e n -sory/perceptua l level, a nd a re less likely to be enga ged

by cognitively demanding emotional tasks, or to cogni-tively elicited emotions (Reima n et al., 1997; Teasdale

et al., 1999).

3 .2 R eca l l i n d u c ti on a n d t h e a n t er i o r ci n g u l a t e.

Si m i l a r t o c o n d i t i o n s w i t h C o g n i t i ve D e m a n d , t h o s ew hich induced emotions by evoking memories or ima g-ery of personally relevant affectively laden events re-quired explicit intensive cognitive effort. Accordingly,

t he recollection/reca ll ind uction of emotion specifi callya c t iv a t e d t h e a n t e r ior ci n gu la t e ; 50% of r eca l l i n -duction studies reported ACC a ctiva tions, versus 31%

a n d 0% of v is ua l a n d a u d it or y in d uct ion s t ud ies ,respectively (X 2 5.96, P 0.05). As describeda bo ve , r e c r u i t m e n t o f t h e AC C w a s s p e c ifi c to cogni-tively demanding emotional tasks, and therefore, thisa ssocia tion suggests tha t reca l led emotions a re cogni-t i ve l y e l i c i t e d , a s n o t e d by R e i m a n et al. (1997) and

40 P H AN E T AL .


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Teasdale et a l. (1999). Given its known cognitive func-ons including modulation of at tention and executive

unctions, and interconnections with subcortical limbictructures, the ACC ’s involvement in cognitive induc-on of emotional response, is not surprising. Such arocess demands cognitive effort , as subjects are in-

tructed to recal l or ima gine an emotiona lly la den per-ona l event t hen self-induce or int ernally genera te in-

ense ta rget emotions (Teasda le et al., 1999). M oreover,he ACC is consistently activated in semantic and ep-sod i c m em or y r e t r ie va l t a s ks (C a bez a a n d N y ber g ,000).

3. 3 R ecall induct ion, cognit ive demand, and t he in-

ula. Nea rly 60%of reca ll induction studies report edctivation of the insula, compared to less than 20%ofi t h e r vi s u a l o r a u d i t o r y i n d u c t i o n s (X 2 8.23, P .02). Like th e ACC , recruit ment of the insula w a s a lso

dentifi ed more w ith cognitively dema nding emotiona la s k s (X 2 7.71, P 0 .01), than with passive emo-o n a l t a s k s . L a n e et a l . (1997c) a nd Reima n et a l .

1997) s pecifi cal ly found t ha t emotiona l reca l l, but notmotional fi lm viewing, engaged the insula. Our fi n d-ngs as w ell as ea rl ier st udies on non-huma n prima tesAugustine et al., 1996) support th e suggestion t ha t t hensula is preferentia l ly involved in t he eva luat ive, ex-eriential , or expressive aspects of internally gener-

t e d e m ot i on s (R e im a n et al. , 1997). I n a s t u d y i nhich multiple specifi c i n d i vi d u a l e m o t i o n s w e r e i n -uced by recall (happiness, sadness, fear, and disgust),a ma sio and collea gues (2000) found th a t a ll emotionsngaged the cingulate, insular cortex, and brainstem.

Their fi n d i n g s a r e con s i st e n t w i t h a n a t o m ic e vid e n ceha t these regions a re direct a nd indirect recipients ofignals from the interna l milieu a nd viscera, w hich a remporta nt in the regulat ion of homeosta sis . Given this

roposed r ole of emotion in ma inta ining h omeosta sis ,a m a s i o et al. (2000) suggest th a t t hese regions, w hile

n ga g e d i n t h e r e ca l l a n d s el f-g en e r a t i on of a f fe ct ,m o n i t o r t h e o n g o i n g i n t e r n a l e m o t i o n a l s t a t e o f t h e

r g a n i s m , a n d m a y r e pr e se n t t h e n e u r a l cor r e la t e s ofm e n t a l s t a t e s kn ow n a s fee li n g s. R e im a n et al. (1997)

a d pos it ed t h a t t h e in su la m a y pa r t i cip a t e i n t h eva l u a t i on of “distressing cognitions, interoceptive

motional s ignifi cance” a s a n a l a r m c e n t e r f o r i n t e r -a l ly-sensed da ngers or homeosta tic cha nges. Such a n

nternal alarm hypothesis is consistent with our fi n d-n g s t h a t t h e i n s u l a i s a s s oci a t e d w i t h bo t h s el f-i n -u c e d o r i n t e r n a l l y g e n e r a t e d r e c a l l e d e m o t i o n s a n dith cognitively demanding tasks.

3. 4 V isual induct ion and t he occipit al cort ex. Theccipita l/visua l cort ex (OC) (ma inly B A 18 a nd 19, butl s o o c c i p i t a l g y r u s a n d fu s i fo r m g y r u s ) w a s a l m o s txclusively a ctiva ted by visually evoca tive st imuli. Of

he 35 visual induction studies, 60% reported a ctiva -on i n t h e O C , w h i ch w e r e r e por t e d i n on l y 2 9% a n d% of reca l l a nd a uditory induction studies, respec-

tively. As a general rule, the studies included in thisreview controlled for activations driven by simple sen-sory processing by designing both the target and con-trol conditions to have similar sensory loads (e.g., con-d it i on s w i t h e mot i on a l ly l a d en v is u a l s t im u li w e r ecompar ed wit h conditions w ith emotiona lly n eutra l vi-sua l stimuli). Often, the pictoria l stimuli were ma tchedfor color , lumina nce, a nd complexity a cross t a rget a nd

con t r o l con d i t ion s . Th e vis u a l s t i m u li t h a t a c t i va t e dO C w e r e d i ve r s e a n d i n c l u d e d p l e a s a n t a n d a ve r s i vepictures (Kosslyn et al., 1996; La ne et al., 1997a; Langet al. , 1998; Reiman et al. , 1997; Taylor et al. , 1998,2000; La ne et al., 1999; P a ra diso et al., 1999; S impsonet al. , 2000; Ka lin et al. , 1997; Irw in et al. , 1997),emotiona l fa ces (Morr is et al ., 1998a; Spr engelmeyer etal. , 1998), and emotional fi l m s ( P a r a d i s o et al. , 1997;L a n e et al., 1997c; Beauregard et al. 1998). The modu-lation of the OC by the emotional components of visualinduction ma y ha ve been d riven by ei ther (1) from t heprocessing of emotionally loaded content or, (2) from an

interaction between visual perception and emotionalprocessing.

Due to i ts engagement across multiple visual emo-tion tasks, i t has been proposed that the OC mediatesa n d a p p r a i s es vi su a l l y r e le va n t , com p le x e m ot i on a lstimuli (Lane et al., 1997a ; B e a u r e ga r d et al. , 1998).Reima n an d collea gues (1997) suggested tha t visualassociation areas in occipitotemporal cortex could beinvolved in t he eva lua tion procedure of complex visualstimuli with emotional relevance. The activations inthe visual cortex were found to be independent of thety pe of emotions by a num ber of aut hors (Kosslyn et al.,

1996; Lane et al., 1997; La ng et al., 1998; Reima n et al.,1997). An alternative interpretation is that the occipi-t a l c o r t e x i s r e c r u i t e d be c a u s e t h e vi s u a l s t i m u l i a r eh i gh l y a r ou s in g , a s s u ch s t i m u li a p pe a r s t o a ct i va t e dperceptual areas more extensively (Lang et al. , 1998;Taylor et al. , 2000). Differences in image complexity,particularly semantic complexity, has been proposedas the underlying mediat or of t he occipita l cortex a cti-vations despite experimental ly balancing for the con-tent of images for luminance, color, and detail (Irwin etal. , 1997; Taylor et al., 2000). For example, visual cor-tex activat ion ma y a lso be at t r ibuted to di fferentia l eye

m ovem e n t s bet w e en e m ot i on a l a n d n on -e m ot i on a lstimuli due t o complexity. H ow ever, La ng et al. (1998)demonstrated no difference in the duration or magni-tude of scanning eye movements between the st imuli ,and Lorge et al . (2000; unpublished da ta ) report ed tha tt h e e xt e n t of e y e m ovem e n t s d i d n ot cor r e la t e w i t hoccipital cortex responses. Another possible contribu-t i on t o t h e a c t i va t i on fou n d i n t h e vi s u a l c or t e x, p a r -t i cu la r l y i n t h e f u s if or m g y r u s, m a y a r i s e f r om t h epresence of fa ces in t he pictoria l a nd fi lm stimuli . How-ever, Simpson et al. (2000) found that the OC activa-tion in t heir study w a s related t o the emotiona l valenceof the pictur es not th e presence of fa ces, a nd su ggested



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hat the presence of faces could not ful ly explain theisua l cort ex/fusiform a ctiva tions. Additional stu diespecifi cal ly examining the effect of image content wil l

be needed to completely ru le out potent ial confoundinga ctiva tions due to visua l complexity a nd/or ar ousal.

One plausible explanation is that visual processing

FIG. 2C. R egiona l a ct iva t ions: Cognit ive dema nd.

42 P H AN E T AL .


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reas may represent top-down modulatory effects onhe visual processing str eam, pa rticula rly in relat ion t o

h e a m y g d a l a , w h i c h w a s a l s o fo u n d t o be s p e c ifi c t oisua l induction. Ana tomically, projections fr om limbic

egions l ike the a mygda la extend to a l l the processingt e p s i n t h e ve n t r a l vi s u a l s t r e a m , i n c l u d i n g t h e p r i -

mary visual cortex (Amaral et al., 1984). A componentf this top-down processing ma y be t he selective at ten-

o n t h a t d r i ve s t h e m o d u l a t i o n o f vi s u a l p r o c e s s i n gCorbetta et al., 1993). Anatomical studies has shown

h a t t h e p r i m a t e a m y g d a l a r e c e i ve s s u bs t a n t i a l i n p u tr om t e m p or a l vi su a l -a s s o ci a t i on a r e a s (I w a i et al. ,987, Aggleton et al., 1980). Both Morris et al. (1998a )n d Sp r e n ge lm e y er et a l . (1998) proposed a neuro-

m od u la t or y fu n ct i on (t o p-d ow n p r oce ss i n g) of t h emygdala on extrastr iate cortical regions after fi ndingn inverse correlation of amygdala and fusiform activ-y i n r e s p o n s e t o fe a r fu l fa c e s . M o r r i s et a l . (1998)

ypothesized that extrastr iate regions have functionaln t er a c t i on s w i t h t h e a m y g d a l a , e vi d en ce d by ot h e r

acial emotion processing studies (George et al., 1993;Adolphs et al., 1996).

3. 5 V isual induct ion and t he amygdala. The visua l

nd u ct i on m et h od a l s o p r ef er en t i a l ly a c t iv a t e d t h emygda la, over r eca l l and a uditory-genera ted emotion.

ifty percent of visual induction studies reported acti-ation of the amygdala, compared to 7%and 0%of recall

nd a uditory inductions, r espectively (X 2 12.93, P .002). Fr om this , one can propose tha t the a mygda la

as a special ized role in processing visually relevantm ot i on a l cu e s, s ig n a l l in g fea r , a ve r s iven e ss , or s a -

ence. Because of its projections to virtually all levelsf visual processing in the occipita l cortex, t he a myg-

ala is posit ioned to modulate visual input, based onmotional signifi cance, a t a var iety of levels along thisisual processing st ream. Hence, a s discussed earl ier ,h e a m y g d a la r a c t iv a t i on s m a y b e p r im a r i ly f or p r o-

essing a ffective inform a tion w ithin t he visua l process-n g s t r e a m i n s e r v i c e o f i m p a r t i n g d a n g e r w a r n i n g s

Da vis a nd Wha len, 2001). S imila rly, others ha ve sug-ested that the amygdalar response to visual emotion-lly st imuli may be in the serviced of assigning emo-

on a l s ig n ifi ca n c e t o s en s or y , p a r t i cu la r l y v is u a l ,

nputs (Simpson et al. , 2000) o r t h a t beca u s e of i t sm od u la t or y i nfl u en ce s, t h e a m y g d a l a m a y f a ci li t a t e

rocessing of sal ient , adaptively signifi c a n t vi s u a l i n -uts (Morris et al., 1998). Given that humans rely onis ion , m or e t h a n h ea r i n g or ol fa c t ion , t o e va l u a t e

hanges in the environment, the amygdala is well po-it ioned to alert us to visual threat fol lowing percep-

on by the occipital cortex.Interestingly, very few recall-driven emotion activa-

on studies engaged the amygdala (at 7%frequency).o m e a u t h o r s h a ve h y p ot h e s iz ed t h a t t h e a m y g d a l a i s

e s s e n g a g e d by r e c a l l e d e m o t i o n s t h a n fo r vi s u a l l y -vocative emotions (Reiman et al., 1997; Da ma sio et al .,

2000). Thus, t he a myg da la ma y be m ore responsible forprocessing of externa lly-cued perceptua l emotionalstimuli (Reiman et al., 1997; Teasdale 1999), and lessinvolved in interna lly genera ted recollection or imag-ery of those stimuli (Reima n et al., 1997; Whalen et al.,1998; Rauch et al., 1999; Shin et al., 2000; Damasio etal. , 2000). Another potentia l issue is tha t ma ny mem-ories recalled are likely to involve more than one emo-

tion (G eorge et al. , 1995), a n d t h e r eby m a y r e d u cesta tist ica l pow er to detect subt le cha nges in the a myg-da lar response, wh ich ma y a lso be selective for certa inemotions. The relationship of self-generated emotionby reca l ling persona l events in a contr olled environ-ment like a PETscanner is clearly phenomenologicallydifferent from the spontaneous and direct experiencet h a t em ot ion in a n a t u r a l s et t i ng (M a y ber g et al. ,1997). An ot h e r p ot e n t i a l e xp la n a t i on of t h e i n fr e -quency of am ygda la a ctiva tion in emotiona l reca l l maybe due to the tempora l rela tionship betw een cha nges inblood fl ow and the behavior in question. Also, the in-

duction of emotions by r eca l l or imagery ma y be moret i m e-con s u m in g t h a n m or e d i r ect p er c ep t u a l i n d u c-tion, making differences in amygdalar responses diffi -cult to detect in PET studies due to l imited temporalresolution, or the time-consuming process may be sus-ceptible to known habituation effects (Breiter et al . ,1996).

CAVEATS AND LIMITATIONS OF REVIEW

Meta-analysis methodologies in general, and this re-view in part icular , ha ve a number of limitat ions w orth

d i scu s s in g . F i r s t , i n t h e s ea r c h for p ot e n t i a l a s s oci a -t i o n s be t w e e n e m o t i o n a n d br a i n a c t i va t i o n , a u t h o r sm a y b e b ia s e d i n r ep or t i n g ce rt a i n a c t iv a t i on s . F ore x a m p l e , be c a u s e t h e a s s o c i a t i o n s be t w e e n fe a r a n dthe amy gdala a nd betw een sadness and the subca llosa lanterior cingulate cortex have gained attention in ac-tiva tion studies of emotion, studies ma y under-reportfa i l u r e s t o fi n d t h e e x p e c t e d a c t i va t i o n s , a n d c o n s e -quently infl ate the probabil i ty of fi nding such a ssocia -t i on s i n a m e t a -a n a l y s is . Se con d , t h e r e i s s u bst a n t i a ld iffi culty in examining results from non-uniform ex-periments. Emotion activation studies differ widely not

only in t he evocative st imulus, induction method, an demotional tasks employed but also in their stat ist icalp o w e r , i n t h e c r i t e r i a u s e d i n d efi ning signifi c a n t r e -s u lt s , a n d i n m e t h od s of p r ep r oce ss in g i m a g i n g d a t a .Su c h fa c t o r s m a y a f fe c t t h e r e s u l t s c o n s i d e r a bl y a n da d d t o t h e d i ve r s e a c t i va t i o n p a t t e r n s t h r o u g h o u t t h ee n t i r e br a i n . T h i r d , t h e r e a r e l i m i t a t i o n s o f t h e s u b-traction method, which produced all the activation focie x a m i n e d i n t h i s r e vi e w . T h e s u bt r a c t i o n m e t h o d i slimited because it does not identify all the regions thata re involved in cert a in emotion/emotiona l ta sk but onlyt h o s e t h a t s h o w a s i g n ifi cant di fference between thetarget and reference condition. Consequently, the re-



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ults are confounded i f the process of interest is not

uccessfully isolat ed (J ennin gs et al., 1997).

B a sed on t he distr ibution of al l a ctiva tion pea ks rep-

esented in the brain renderings (Fig. 1), one al terna-

ve interpreta tion is th a t emotiona l ta sks involve mul-

p l e r e g i o n s t h r o u g h o u t t h e e n t i r e br a i n a n d d o n o t

onclusively point to any particular functional special-

zation, and that these regions are not disproportion-

t e ly i m por t a n t t o a n y on e e m ot i on . Th i s i n t e r p r et a -on w ou ld su gg est t ha t br a in r eg ion s a r e n ot

ommitted to specifi c emotions or induction method,

u t r a t h e r m a y be i n vol ve d i n a va r i e t y o f e m ot i on a l ,

ognitive-emotion, or nonemotiona l executive ta sks.

However, compar isons using frequency of a ctiva tion

percenta ge of studies r eporting) a nd chi-squa re a na l-

ses (Fig. 2) provide support the a ssocia tions w e ha ve

dentifi e d i n t h i s r e v i e w . I t s h o u l d b e r e a s o n a b l e t oxpect that s ignifi cant results from separate indepen-

ent studies would be rel iable data. Nevertheless, we

onsider the a ssociat ions identifi e d i n t h i s m e t a -a n a l -sis as preliminary and would caution readers against

remature conclusions about functional specialization.

We a lso a cknowledge other l imita tions specifi c t o

his review. First , while we separa ted “Emotion Alone”a s ks fr om t h o se w i t h “Cognitive Demand” in order to

xa mine t he effect of a cognitive “nonemotional” com-onent on passive emotional responses, this classifi ca -

on c a n be a r g u ed a s s om e w h a t a r bit r a r y . So m e t a s ks

abeled a s “w i t h C o gn i t ive D e m a n d ” (e.g., gender iden-

fi ca t i on ) m a y b e r e g a r d ed a s a n on cog n it i vel y d e-ma nding. We would a rgue tha t w hen compar ed to pa s-

ive e m ot i on a l t a s ks (e .g . , v ie w i n g e m ot i on a l fa c eslone), such acts require that subjects make an overt

iscrimina tion/cat egoriza tion a nd a dd a decision-ma k-

ng component, thereby rendering i t more “cognitive”han passive viewing (even i f the addit ional cognitive

oad may be small). However, the heterogeneity of cog-

itive tasks employed by different experiments should

e kept in m ind w hen interpreting th e results . S econd,

e d i d n o t i n cl u d e i m a g i n g s t u d i es e xa m i n i n g fe a r ,

versive, and tra ce conditioning in t his review, ma inly

eca use the a cquisit ion a nd extinction t a sks exa mined

n t h e se p a r a d i gm s a r e n ot com p a r a b le t o t h e o t h ermotiona l ta sks employed by t he 55 stu dies included in

u r d a t a ba s e . I f i n c l u d e d , t h e r e m a y h a ve be e n a d d i -

o n a l e vi d e n c e fo r t h e a s s o c i a t i o n be t w e e n fe a r a n d

h e a m y g d a l a , w h i c h i s s u p p o r t e d b y t h e fi ndings ofü chel and Dolan (2000) in their review of this litera-

ure. We acknowledge tha t the decision not t o include

ndings from conditioning studies may have affected

h e r e su l t s o f t h i s r e vi ew . F i n a l l y , t h e l im i t ed r e pr e -

enta tion of certa in induction methods (e.g. , a uditory)

nd individual emotions (e.g. , anger, disgust) lowers

h e s t a t i s t i ca l p ow e r t o fu r t h e r d et e ct fu n ct i on a l a n a -

omic specifi city.

CONCLUSION

To our knowledge, this is the fi rst meta-analysis offunctiona l neuroima ging studies involving emotion.U s i n g d a t a o bt a i n e d fr o m a c o l l e c t i o n o f s t u d i e s , w eexamined if specifi c brain regions w ere associat ed withemotiona l activa tion in general, different emotions, dif-fer e n t i n d u ct i on m e t h od s , a n d cog n i t ive e m ot i on a l

t a s ks . O u r m e t a - a n a l y s i s y i e l d e d t h e fo l l o w i n g s u m -mary observations: (1) The medial prefrontal cortexappeared to have a general role in emotional process-ing across al l categories and domains of interest ; (2)fear specifi cal ly engaged the a mygda la; (3) sad ness wa sa ssociat ed with a ctivity in the subcallosal cingula te; (4)induction by visua l st imuli a ctivated the occipita l cor-t e x a n d t h e a m y g d a l a ; (5) i n d u ct i on by e m ot i on a l r e -ca l l/imagery recruited t he a nterior cingulat e a nd in-s ula ; (6) em ot ion a l t a s k s w i t h cog n it iv e d em a n dpart icularly involved the an terior cingula te a nd insula.O u r m e t a -a n a l y s i s fu r t h e r d el in e a t e s d i scr e t e br a i n

r e gi on s t h a t a r e i n vol ve d i n va r i ou s e m ot i on a l t a s ks .M a n y of t h e se i m p li ca t e d a r e a s a n d t h e ir p ut a t i vefu n ct i on a l r ol es a r e con s i st e n t w i t h d a t a p r eviou s lyprovided from a na tomic descriptions, a nimal experi-ments, and human lesion studies.

Se ver a l m e t h od ol og ica l a p p r oa c h es w o u ld p ot e n -tia l ly improve the rel ia bili ty a nd val idi ty of identi fyingspecifi c brain regional involvement in emotion a nd t heabil i ty t o ma ke meaningful compar isons a cross stu diesin subsequent meta -a na lyses. Fut ure studies could usem or e u n i for m , s t a n d a r d s t i m u li a n d d e si g n a ct i va t i onparadigms with careful exact isolation of the emotional

process of int erest. The effect of individua l differencesin bra in a ctivation could be exa mined by par a metric orfa c t or i a l d e si gn s (e .g . , cor r e la t i on w i t h beh a vi or a l /p h y s iol og ic i n d ice s) or by p er s on a l it y a n d t e m pe r a -ment measures. Specifi c a c t i va t i on s cou l d be fu r t h e risolat ed t hrough “conjunction” a n d “network” a n a l y s esor event-related designs (Ca beza a nd Nyberg, 2000).Though future neuroimaging studies will no doubt addto our current understa nding functiona l brain segrega-tion and connectivity for emotional operations, the pat-t e r n s a n d r e g ion s i d en t ifi ed in this review are impor-t a n t con s t i t u en t s of t h e fu n ct i on a l n e u r oa n a t om y of

emotion.

REFERENCES

A b ercromb ie, H. C. , Scha efer , S. M . , L a rs on, C. L . , Wa rd, R . T. ,

Holden, J . F . , Tu rs ki, P . A. , P erlma n, S . B . , a nd Da vids on, R . J .

1996. M edia l p refront a l a nd a mygda la r glu cose m et a b olis m in

depressed and control subjects: an FDG-PET study. Psychophysi-

ology 33: S17.

Adolphs, R., Tra nel, D., Da ma sio, H., a nd D am asio, A. R. 1995. Fear

a n d t h e h u m a n a m y g d a l a . J . N eur osci. 15: 5879 –5891.

A dolp hs , R . , Da ma s io, H. , Tra nel, D. , a nd Da ma s io, A . R . 1996.

Cortical systems for the recognition of emotion in facial expres-sions. J . N eur osci. 16: 7678 –7687.

44 P H AN E T AL .


15/18

gglet on, J . P . , a nd M is hkin, M . 1990. V is u a l imp a irment s in m a -

caques following inferior temporal lesions are exacerbated selec-

t ively b y a ddit iona l da ma ge t o s u p erior t emp ora l s u lcu s . Behav.

Brain Res. 39: 262–274.

mara l, D. G ., and P rice, J . L. 1984. Amyg da lo-cort ical projections in

the m onkey (Macaca fascicular is). J. Comp. Neurol. 230: 465– 496.

nderson, S. W., Bechara , A., Dam asio, H., Tra nel, D., and D am asio,

A . R . 1999. I mp a irment of s ocia l a nd mora l b eha vior rela t ed t o

ea rly da ma ge in hu ma n p refront a l cort ex. N at. N eur osci. 2: 1032–

1037.ugustine, J . R. 1996. Circuitry an d functional a spects of th e insular

lob e in p rima t es inclu ding hu ma ns . Br a in R e s . Br a in R e s . R e v .

229 –244.

a ker, S. C . , Frit h, C . D . , a nd Dola n, R . J . 1997. The int era ct ion

between mood and cognitive function studied with PET. Psychol.

Me d . 27: 565–78.

a xt er , L . R . J r . , P helps , M . E . , M a z z iot t a , J . C. , Schwa rt z , J . M . ,

G e r n e r , R . H . , S e l i n , C . E . , a n d S u m i d a , R . M . 1 9 8 5 . C e r e b r a l

m e t a b ol ic r a t e s f or g l uc os e i n m ood d i sor d er s . S t u d i es w i t h

positron emission tomography and fl uorodeoxyglucose F 18. Ar ch .

Gen. Psychi atr y. 42: 441– 447.

ea u rega rd, M . , Chert kow, H. , B u b , D. , M u rt ha , S. , Dixon, R . , a nd

E va ns , A. 1997. The n eu ra l s u b s t ra t e for concret e, a b s t ra ct , a nd

emotional word lexica: A positron emission tomography study. J .

Cogni t. N eur osci. 9: 441– 461.

ea u rega r d, M . , L eroux, J . M . , B ergma n, S . , Yerva nt , A ., G il les , G ,

Bourgouin, P. , and Stip, E. 1998. The functional neuroanatomy of

ma jor dep res s ion: A n fM R I s t u dy u s ing a n emot iona l a ct iva t ion

p a ra digm. NeuroReport 9: 3253–3258.

echa ra , A., Tra nel, D., Da ma sio, H., Adolphs, R., Rocklan d, C., a nd

Damasio, A. R. 1995. Double dissociation of conditioning and de-

cla ra t ive knowledge rela t ive t o t he a m ygda la a nd hip poca mp u s in

h u m a n s . Science 269: 1115–1118.

la ir , R . J . R . , M orris , J . S. , Frit h, C. D. , P erret t , D. I . , a nd D ola n,

R. J . 1999. D issociable neura l responses t o fa cial expressions of

s a dnes s a nd a nger. B r a i n 122: 883– 893.

lood, A . J . , Z a t orre, R . J . , B ermu dez , P . , a nd E va ns , A. C . 1999.

E mot iona l res ponses t o p lea s a nt a nd u np lea s a nt mu s ic correla t e

wit h a ct ivit y in p a ra limb ic b ra in regions . Nat. Neurosci. 2: 382–

387.

reit er , H . C . , E t coff , N . L . , Wha len, P . J . , Kenedy, W. A ., R a u ch,

S . L . , B u ck n er , R . L . , S t r a u s s , M . M ., H y m a n , S . E . , a n d R os en ,

B . R . 1 9 9 6 . R e s p o n s e a n d h a b i t u a t i o n o f t h e h u m a n a m y g d a l a

during visual processing of fa cial expression. N eur on 17: 875– 887.

r e i t e r , H . C . , G o l l u b , R . L . , W e i s s k o f f , R . M . , K e n n e d y , D . N . ,

M a k r is , N . , B e r ke , J . D . , G ood m a n , J . M ., K a n t o r , H . L . , G a s t -

f r ie n d, D . R . , R i or d e n, J . P . , M a t h e w , R . T. , R o se n , B . R . , a n d

Hym an , S. E . 1997. Acute effects of cocaine on hum an brain activ-

it y a nd emot ion. Neuron 19: 591– 611.

remner, J . D., St aib, L. H ., Kaloupek, D., South wick, S. M., Soufer,R . , a n d C h a r n e y , D . S . 1 9 9 9 . N e u r a l c o r r e l a t e s o f e x p o s u r e t o

t ra u ma t ic p ict u res a nd s ou nd in V iet na m comb a t vet era ns wit h

a nd wit hou t p os t t ra u ma t ic s t res s dis order: A p os it ron emis s ion

t omogra p hy s t u dy. B io l . Ps ych ia tr y 45: 806 – 816.

rody, A. L. , Saxena, S. , Silverman, D. H., Alborzian, S. , Fairbanks,

L . A. , P help s , M . E . , Hu a ng, S . C. , Wu , H. M . , M a idment , K. , a nd

B a xt er , L . R . J r . 1999. B ra in met a b olic cha nges in ma jor dep res -

sive disorder from pre- to post-trea tment wit h pa roxetine. Psychi-

atry Res. 91: 127–139.

üchel, C. , M orris , J ., Dola n, R . J . , a nd Fris t on, K. J . 1998. B ra in

s ys t ems media t ing a vers ive condit ioning: a n event -rela t ed fM R I

s t u dy. N eur on 20: 947–957.

üchel, C . , D ola n, R . J . , A rmony J . L . , a nd Fris t on, K. J . 1999.Amygda la-hippocampal involvement in huma n a versive trace con-

ditioning revealed through event-related functional magnetic res-

ona nce ima ging. J . N eur osci. 19: 10869 –10876.

B ü chel, C . , a nd Dola n, R . J . 2000. Cla s s ica l fea r condit ioning in

functional neuroimaging. C u r r . O p in . N e u r o b io l . 10: 219 –223.

B u s h, G . , L u u , P . , a nd P osner, M . I . 2000. Cognit ive a n d emot iona l

in fl uences in anterior cingulate cortex. Trends Cogn. Sci. 4: 215–

222.

Cabeza, R., and Nyberg, L. 2000. Imaging cognition II : An empirical

review of 275 PET and fMRI studies. J . Cogn. N eur osci. 12: 1– 47.

Calder, A. J ., Young, A. W., Rowland, D., Perrett, D. I., Hodges, J . R.,

and Etcoff, N. L. 1996. Facial emotion recognition after bilateral

a mygda la da ma ge: Dif ferent ia lly s evere imp a irment of fea r . Cogn.

Neuropsychol. 13: 699 –745.

Ca nli , T. , Des mond, J . E . , Z ha o, Z . , G lover, G . , a nd G a b rieli , J . D.

1998. Hemispheric asymmet ry for emotional stimuli detected w ith

fMRI. NeuroReport 9: 3233–3239.

Casey, K. L. , Minoshima, S. , Berger, K. L. , Koeppe, R. A., Morrow,

T. J ., an d Fr ey, K. A. 1994. Positr on emission tomogra phic ana lysis

of cerebral structures activated specifi cally by repetitive noxious

hea t s t imu li. J. Neurophysiol. 71: 802– 807.

Cechetto, D. F. , a nd S aper, C . B . 1990. Role of the cerebral cortex in

aut onomic function. In Central Regulation of Autonomic Functions

(A. D. Loewy a nd K. M. S pyer. Eds.) Oxford U niv. Pr ess, New York.

C o r b e t t a , M . , M i e z i n , F . M . , S h u l m a n , G . L . , a n d P e t e r s e n , S . E .

19 93 . A P E T s t u d y of v i su os pa t i a l a t t e n t i on . J . N e u r osci . 13:

1202–1226.

Cros son., B . , R a ndonovich, K . , Sa dek, J . R . , G okca y, D . , B a u er, R . ,

Fischler, I . , Cato, M. A., Maron, L. , Auerbach, E. J . , Browd, S. R.,

an d B riggs, R. W. 1999. Left-hemisphere processing of emotional

connotation during word generation. NeuroReport 10: 2449–2455.

Da ma s io, A . R . 1994. D eca r tes’ Er r o r : Em otio n , R ea son , a n d th e

H u m a n B r a i n . Avon Books, New York.

Da ma s io, A. R . , G ra b ows ki, T. J ., B echa ra , A ., D a ma s io, H . , P ont o,

L . L . B . , P a r v iz i, J . , a n d H i ch w a , R . D . 2 000 . S u b cor t i ca l a n d

cort ica l b ra in a ct ivit y du ring t he feeling of s elf-genera t ed emo-

tions. Nat. Neurosci. 3: 1049 –1056.

Da vidson, R. J . , Ekma n, P . , Sa ron, C., Senulis, J ., an d Fr iesen, W. V.

1990. Ap proa ch/wit hdra wa l a nd cereb ra l a s ymmet ry: E mot iona l

expression a nd bra in physiology. I . J . Pers. Soc. Psychol. 58: 330 –

341.

Da vidson, R. J . , and Irw in, W. 1999. The functional n euroana tomy of

emotion and affective style. T rends Cogn. Sci. 3: 11–21.

Da vis , M . , a nd Wha len, P . J . . 2001. The a mygda la : V igila nce a nd

emotion. M ol . Ps y ch ia tr y 6: 13–34.

Devinsky, O., Morrell, M. J ., a nd Vogt, B . A. 1995. Contr ibutions of

anterior cingulate cortex to behaviour. B r a i n 118: 279 –306.

Dola n, R. J . 1998. A cognitive a ffective role for the cerebellum. B r a i n

121: 545–546.

Dola n, R . J . , L a n e, R . , Chu a , P . , a nd Flet cher, P . 2000. Dis s ocia b le

t emp ora l lob e a ct iva t ions du ring emot iona l epis odic memory re-

t r ieva l . N eu r o Im a g e 11: 203–209. doi:10. 1006/ni mg .2000.0538.

Dougherty, D . D., Shin, L. M., Alpert, N. M., Pitm an , R. K., Orr, S. P. ,

Lasko, M., Macklin, M. L., Fischman , A. J . , an d Ra uch, S. L. 1999.

Anger in healthy men: A PET study using script-driven imagery.

Bio l . Psy ch ia tr y 46: 466 – 472.

Dr evets, W. C., P rice, J . L., S impson, J . R., J r, Todd, R. D ., Reich, T.,

Vannier, M., an d Ra ichle, M. E. 1997. Subgenua l prefrontal cortex

abnormalities in mood disorders. N a t u r e 386: 824 – 827.

Drevets, W. C., and Raichle, M. E. 1998. Reciprocal Suppression of

R egiona l Cereb ra l B lood Flow du ring E mot iona l versu s H igher

Cognitive P rocesses: Implicat ions for intera ction betw een Emotion

a nd Cognit ion. Cogn. Emotion 12: 353–385.



16/18

uncan, J . , and Owen, A. M. 2000. Common regions of the human

frontal lobe recruited by diverse cognitive demands. T r en d s N eu -

rosci. 23: 475– 483.

verit t , B . J ., M orris , K. A . , O’Brien, A., and Robbins, T. W. 1991.

The b a s ola t era l a mygda la -vent ra l s t r ia t a l s ys t em a nd condit ioned

place preference: Further evidence of limbic-striatal interactions

underlying reward-related processes. N eur oscience 42: 1–18.

ox, P . T. , P a rs on, L . M . , a nd L a nca s t er , J . L . 1998. B eyond t he

single stud y: F unction/locat ion meta na lysis in cognitive n euroim-

a ging. C u r r . O p i n . N e u r o b i o l . 8:

178 –187.rey, S . , Kos t opou los, P . , a nd P et rides , M . 2000. Orb it ofront a l in-

volvement in t he p roces s ing of u np lea s a nt a u dit ory informa t ion.

E u r . J . N eu r o sci . 12: 3709–3712.

ema r, M . C. , Ka p u r, S. , Sega l , Z . V . , B rown, G . M . , a nd Hou le, S.

1996. Effects of self-generated sad mood on regional cerebral ac-

t ivit y: A P E T st u dy in norma l s u b ject s . D epr essi on 4: 81– 88.

eorge, M . S. , K et t er , T. A . , G il , D. S. , H a xb y, J . V. , U ngerleider,

L . G . , a nd Hers covit ch, P . , a nd P os t , R . 1993. B ra in regions in-

volved in recognizing facial emotion or identity: An oxygen-15 PET

s t u dy. J. Neuropsychiatry Clin. Neurosci. 5: 384 –394.

eorge, M. S. , Ketter, T. A., Parekh, P. I . , Horwitz, B. , Herscovitch,

P . , a nd P os t , R . M . 1995. B ra in a ct ivit y du ring t ra ns ient s a dnes s

a nd ha p p ines s in hea lt hy women. Am. J. Psychiatry 152: 341–351.

eorge, M . S. , P a rekh, P . I . , R os ins ky, N . , K et t er , T. A . , Kimb rell ,

T. A . , Heilma n, K. M . , Hers chovit ch, P . , a nd P os t , R . M . 1996a .

U nders t a n ding emot iona l p ros ody a ct iva t es r ight hemisp here re-

gions. A r ch . N eu r o l . 53: 665– 670.

eorge, M. S. , Ketter, T. A., Parekh, P. I . , Herscovitch, P. , and Post,

R. M. 1996b. Gender differences in regional cerebral blood fl ow

during transient self-induced sadness or happiness. Biol. Psychi-

a t r y 40: 859 – 871.

ra y, J . A. 1982. Th e N eur opsychology of Anxi ety. Oxford U niv.

Press, New York.

algren, E. , Walter, R. D., Cherlow, D. G., and Crandall, P. H. 1978.

Mental phenomena evoked by electrical stimulation of the human

hip p oca mp a l forma t ion a nd a mygda la . B r a i n 101: 83–117.

a m a n n , S . B . , E l y , T . D . , G r a f t o n , S . T . , a n d K i l t s , C . D . 1 9 9 9 .

A mygda la a ct ivit y rela t ed t o enha nced memory for p lea s a nt a nd

aversive stimuli. Nat. Neurosci. 2: 289 –293.

a rir i , A. R . , B ookheimer, S . Y. , a nd M a z z iot t a , J . C. 2000. M odu -

lat ing emotional responses: Effects of a neocortical net work on th e

limbic system. NeuroReport 11: 43– 48.

u t chins on, M . , Schiffer , W. , J oseffer , S. , L iu , A. , Schlos s er , R . ,

Dikshit , S. , G oldberg, E . , an d B rodie, J . D. Task-specifi c dea ct iva -

t ion p a t t erns in fu nct iona l ma gnet ic res ona nce ima ging. M a g n .

Reson. Imag. 17: 1427–1436.

win, W., Davidson, R. J ., Lowe, M. J ., Mock, B. J ., Sorenson, J . A.,

and Turski, P. A. 1996. Human amygdala activation detected with

echo-planar functional magnetic resonance imaging. NeuroReport

7: 1765–1769.enberg, N., Silbersweig, D., Engelien, A., Emmerich, S. , Ma lava de,

K. , B ea t t ie, B . , L eon, A . C. , a nd St ern, E . 1999. L ingu is t ic t hrea t

a c t i v a t e s t h e h u m a n a m y g d a l a . P r o c . N a t l . A c a d . S c i . U S A 96:

10456–10459.

wa i, E . , Yukie, M . , Su ya ma , H. , a nd Shira ka wa , S. 1987. Amygda la r

connections with m iddle and inferior temporal gy ri of the monkey.

Neurosci. Lett. 83: 25–9.

ennings, J . M., McInt osh, A. R., Ka pur, S. , Tulving, E . , an d H oule,

S. 1997. Cognitive subtractions may not add up: The interaction

between semantic processing and response mode. N eu r o I m a g e 5:

229 –239.

a lin, N . H. , D a vids on, R . J . , I rw in, W. , Wa rner, G . , Orendi, J . L . ,

Sutton, S. K., Mock, B. J . , Sorenson, J . A., Lowe, M., and Turski,P . A . 1997. Fu nct iona l ma gnet ic res ona nce ima ging s t u dies of

emotional processing in normal and depressed patients: Effects of

venlafaxine. J . C l i n . P sy ch i a t r y 58(S16): 32–39.

Ket t er , T. A . , Andrea s on, P . J ., G eorge, M . S . , L ee, C. , G il l , D. S. ,

P ar ekh, P . I . , Willis, M. W., Herscovitch, P . , an d P ost, R. M. 1996.

Anterior pa ra limbic mediation of procaine-induced emotiona l a nd

psychosensory experiences. Ar ch. G en. Psychi atry 53: 59 – 69.

Kimbrell, T. A., George, M. S. , Parekh, P. I . , Ketter, T. A., Podell,

D. M., D a nielson, A. L., Repella , J . D., B enson, B . E., Willis, M. W.,

Hers covit ch, P . , a nd P os t , R . M . 1999. R egiona l b ra in a ct ivit y

during transient self-induced anxiety and anger in healthy adults.Biol. Psychiatry 46: 454 – 65.

King, A. S., and Brothers, L. A. 1992. TheAmygdala: Neurobiological

Aspects of Em otion, M emory, and M ental Dysfuncti on (J . P. Aggle-

ton, Ed.), pp. 355–377. Wiley-Liss, New York.

Kluver, H., and B ucy, P. C. 1939. Prelimina ry a na lysis of functions of

the t empora l lobes in m onkeys. Arch. Neurol. Psychiatry 42: 979 –

1000.

Koch, M., Schmid, A., and Schnitzer, H. U. 1996. Pleasure-attenua-

t ion of s t a rt le is dis ru pt ed b y lesions of t he nu cleu s a ccu mb ens.

NeuroReport 7: 1442–1446.

Koep p, M . J . , G u nn, R . N . , L a wrence, A. D. , Cu nningha m, V . J . ,

Da gher, A., J ones, T., Brooks, D. J . , Bench, C. J . , and Gr asby, P . M.

1998. Evidence for str iat al d opam ine release during a video gam e.

N a t u r e 393: 266 –268.

Koob, G . F. 1992. Neurobiological m echa nisms of cocaine a nd opiat e

dependence. In Addict ive States (C . P . O ’B r i e n a n d J . H . F a f fe ,

Eds.) Raven Press, New York.

Kosslyn, S. M., Shin, L. M., Thompson, W. L., McNally, R. J ., Rauch,

S. L . , P it ma n, R . K. , a nd A lp ert , N . M . 1996. N eu ra l ef fect s of

visualizing and perceiving aversive stimuli: A PET investigation.

NeuroReport 7: 1569 –1576.

LaBar, K. S. , LeDoux, J . E. , Spencer, D. D., and Phelps, E. A. 1995.

Impa ired fear condition following unilat eral t empora l lobectomy in

h u m a n s . J. Neurosci. 15: 6846 – 6855.

L a B a r, K. S. , G a t enb y, J . C. , G ore, J . C. , L eDou x, J . E . , a nd P h elp s ,

E . A . 1998. Hu ma n a mygda la a ct iva t ion du ring condit ioned fea r

acquisition and extinction: A mixed-trial fMRI study. Neuron 20:937–945.

L a n e , R . D . , R e i m a n , E . M . , A h e r n , G . L . , S c h w a r t z , G . E . , a n d

Davidson, R. J . 1997a. Neuroanatomical correlates of happiness,

s a dnes s , a nd dis gu st . A m . J . P sy ch i a t r y 154: 926 –933.

Lan e, R. D., Reiman , E. M., Bra dley, M. M., Lan g, P. J . , Ahern, G . L. ,

D a v i d s on , R . J . , a n d S c h w a r t z , G . E . 1 997 b. N eu r oa n a t om i ca l

correla t es of p lea s a nt a nd u np lea s a nt emot ion. Neuropsychologia

35: 1437–1444.

Lan e, R. D., Fink, G. R., Cha u, P . M., and D olan, R. J . 1997c. Neura l

a ct iva t ion du ring s elect ive a t t ent ion t o s u b ject ive emot iona l re-

sponses. NeuroReport 8: 3969 –3972.

Lane, R. D., Reiman, E. M., Axelrod, B. , Yun, L. S. , Holmes, A., and

Schwa rt z , G . E . 1998. N eu ra l correla t es of levels of emot iona lawareness. Evidence of an interaction between emotion and atten-

tion in the a nterior cingulate cortex. J . Cogn. N eur osci. 10: 525–35.

Lane, R. D., Chua, P. M., and Dolan, R. J . 1999. Common effects of

emotional valence, arousal and attention on neural activation dur-

ing visua l processing of pictures. Neuropsychologia 37: 989 –997.

L a ne, R . D. , a nd N a del, L . ( E ds . ) 2000. Cognitive Neuroscience of

E m o t i o n . Oxford Univ. Press, New York.

L a n g , P . J . , G r e e nw a l d , M . K . , B r a d l ey , M . M . , a n d H a m m A. O .

1993. Looking at pictures: Affective, facial, visceral, and behav-

ioral reactions. Psychophysiology 30: 261–273.

L a n g , P . J . , B r a d l ey , M . M . , F i t z s im m on s , J . R . , C u t h b er t , B . N .,

Scott , J . D., Moulder, B. , and Nangia, V. 1998. Emotional arousal

and activation of the visual cortex: An fMRI analysis. Psychophys-iology 35: 199 –210.

46 P H AN E T AL .


17/18

eDoux, J . E. 1993. Emotional memory sy stems in t he brain . Behavi.

Brain Res. 58: 69 –79.

eDoux, J . E. 1996. T h e E m o t i on a l B r a i n . Simon & Schuster, New

York.

eDoux, J . E. 2000. Emotion circuits in the brain. Annu. Rev. Neu-

rosci. 23: 155–184.

iberzon, I . , Taylor, S. F. , Fig, L. M., Decker, L. R., Koeppe, R. A.,

an d Minoshima , S. 2000. Limbic activa tion a nd psychophysiologic

res p ons es t o a vers ive vis u a l s t imu li . I nt era ct ion wit h cognit ive

t a s k . Neuropsychopharmacology 23: 508 –516.iotti, M., May berg, H. S. , Bra nna n, S. K., McGinnis, S. , J erabek, P. ,

a nd Fox, P . T. 2000. Dif ferent ia l l imbic– cort ica l correla t es of

sadness and anxiety in healthy subjects: Implications for affective

disorders. Biol. Psychiatry 48: 30 – 42.

MacLean, P . D. 1952. Some psychiat ric implicat ions of physiological

studies on the frontotemporal portion of limbic system (visceral

brain). El ectroencephal ogr. Cli n. Neurophysiol. 4: 407– 418.

Maddock, R. J ., and Buonocore, M. H. 1997. Activation of left poste-

rior cingulate gyrus by the auditory presentation of threat-related

words: An fMRI study. Psychiatry Res. 75: 1–14.

Madd ock, R . J . 1999. The retrosplenial cortex an d emotion: New

insights from functional neuroimaging of the human brain. Tr en d s

Neurosci. 22: 310 –316.

M a yb erg, H. S. , L ew is , P . J ., R egenold, W. , a nd Wa gner, H. N . J r .

1994. Paralimbic hypoperfusion in unipolar depression. J . N u cl .

Med. 35: 929 –934.

M a yb erg, H. S. , L iot t i , M . , B ra nna n, S. K. , M cG innis , S. , M a hu rin,

R . K. , J era b ek, P . A. , S ilva , J . A. , Tekell , J . L . , M a rt in, C. C. ,

La ncaster, J . L . , a nd Fox, P . T. 1999. Reciprocal limbic-cortical

fu nct ion a nd nega t ive mood: Converging P E T fi ndings in depres-

s ion a nd norma l s a dnes s . A m . J . P s ych i a t r y 156: 675– 82.

Mayberg, H. S. , Brannan, S. K., Tekell, J . L. , Silva, J . A., Mahurin,

R. K., McGinnis, S. , and J erabek, P. A. 2000. Regional metabolic

effects of fl uoxetine in major depression: Serial changes and rela-

tionship t o clinical response. Biol. Psychiatry. 2000 48: 830 – 843.

Morgan, M. A., Romanski, L. M., a nd L eDoux, J . E. 1993. Ext inction

of emot iona l lea rning: Cont rib u t ion of media l p refront a l cort ex.Neurosci. Lett. 163: 109 –113.

Morris, J . S. , Frith, C. D., Perrett , D. I . , Rowland, D., Young, A. W.,

Ca lder, A. J . , an d D olan, R. J . 1996. A differential neura l response

in t he hu ma n a mygda la t o fea rfu l a nd ha p p y fa cia l exp res s ions .

N a t u r e 383: 812– 815.

Morris, J . S. , Friston, K. J . , Bü chel, C. , Frith, C. D., Young, A. W.,

Ca lder, A. J . , a nd Dolan, R. J . 1998a. A neuromodulat ory role for

t he h u ma n a mygda la in p roces sing emot iona l fa cia l expres s ions.

B r a i n 121: 47–57.

M orris , J . S. , Ohma n, A. , a nd Dola n, R . J . 1998b . C onsciou s a nd

u ncons ciou s emot iona l lea rning in t he hu ma n a mygda la . N a t u r e

393: 467– 470.

M or r i s, J . S . , S c ot t , S . K . , a n d D o la n , R . J . 1 99 9. S a y i n g i t w i t hfeeling: Neura l responses t o emotiona l vocalizations. Neur opsycho-

logia 37: 1155–1163.

a ka mu ra , K. , Kwa s hima , R . , I t o , K. , Su giu ra , M . , Ka t o, T. , N a ka -

m u r a , A ., H a t a n o, K . , N a g u m o , S . , K u t o ba , K . , F u k u da , H . , a n d

Kojima , S. 1999. Act iva t ion of t he r ight inferior front a l cort ex

du ring a s s es ment of fa cia l emot ion. J. Neurophysiol. 82: 1610 –

1614.

’D o h er t y , J . , K r i n ge lb a ch , M . L . , R ol ls , E . T. , H o r n a k , J . , a n d

Andrews , C. 2001. A bs t ra ct rewa rd a nd p u nishment repres ent a -

tions in the human orbitofrontal cortex. N at. N eur osci. 4: 95–102.

an ksepp, J . 1998. Affect ive N eur oscience: T he F oundati ons of H u-

m a n a n d A n i m a l E m o t i o n s . Oxford Univ. Press, New York.

apez, J . W. 1937. A proposed mechanism of emotion. Arch. Neurol.Psychiatry 38: 725–743.

P a ra dis o, S . , R obins on, R . G . , Andrea s en, N . C . , Downhill , J . E . ,

Davidson, R. J . , Kirchner, P. T., Watkins, G. L. , Ponto, L. L. , and

Hichwa , R . D. 1997. E mot iona l a ct iva t ion of l imb ic circu it ry in

elderly norma l s u b ject s in a P E T s t u dy. A m . J . P s y c h i a t r y . 154:

384 –389.

P a r a d i s o, S . , J oh n s on , D . L . , A n d re a s en , N . C . , O’L e a r y , D . S . ,

Wa t kins , G . L . , P ont o, L . L . , a nd Hichwa , R . D. 1999. Cereb ra l

blood fl ow cha nges a s s ocia t ed wit h a t t r ib u t ion of emot iona l va -

lence t o p lea s a nt , u np lea s a nt , a nd neu t ra l vis u a l s t imu li in a P E T

study of normal subjects. A m . J . P s ych i a t r y 156: 1618 –1629.

P ar do, J . V., Pa rdo, P. J . , and Ra ichle, M. E. 1993. Neural correlat es

of self-induced dysphoria. A m . J . P sy ch i a t r y 150: 713–719.

P ar tiot, A., Gra fman , J . , Sad at o, N., Wachs, J ., and Ha llett , M. 1995.

Brain activation during the generation of non-emotional and emo-

t iona l p la ns . NeuroReport 6: 1397–1400.

P etrides, M., and P an dya , D. N. 1999. Dorsolatera l prefronta l cortex:

comp a ra t ive cyt oa rchit ect onic a na lys is in t he hu ma n a nd t he m a -

caque brain and corticocortical connection patterns. E u r . J . N eu -

rosci. 11: 1011–1036.

P ietrini, P. , Gu azzelli, M., Ba sso, G., J affe, K., and G ra fman , J . 2000.

N eu ra l correla t es of ima gina l a ggres s ive b eha vior a s s es s ed b y

positron emission tomography in healthy subjects. Am. J. Psychi-

a t r y 157: 1772–1781.

Phillips, M. L., Young, A. W., Senior, C. , Brammer, M., Andrew, C.,Ca lder, A. J . , Bullmore, E. T., Perr ett , D . I . , Rowlan d, D., Williams,

S. C. , G ra y, J . A . ,, a nd Da vid, A. S . 1997. A s pecifi c neu ra l s u b -

s t ra t e for p erceiving fa cia l expres sions of dis gu s t . N a t u r e 389:

495– 498.

P hillips, M. L., Young, A. W., Scott , S . K., C alder, A. J ., Andrew, C .,

Gia mpietro, V., Williams, S. C . , Bullmore, E. T., Bra mmer, M., an d

Gr ay , J . A. 1998a. Neura l responses to fa cial a nd vocal expressions

of fea r a nd dis gu s t . Pr oc. R. Soc. L ond. B. B iol. Sci. 265: 1809 –17.

P hill ip s , M . L . , B u llmore, E . T. , Howa rd, R . , Woodru ff , P . W. R . ,

Wright, I . C. , Williams, S. C. R., Simmons, A., Andrew, C., Bram-

mer, M., an d D avid, A. S. 1998b. Investiga tion of facial r ecognition

memory and happy and sad facial expression perception: an fMRI

s t u dy. Psychiatr y R es. N eur oimag. 83: 127–138.

Raichle, M. E., MacLeod, A. M., Snyder, A. Z. , Powers, W. J . , Gus-

na rd, D. A., an d Sh ulman , G. L. 2001. Medial prefronta l cortex an d

self-referential ment al a ctivity: Relation to a d efault m ode of brain

function. P r o . N a t l . A c ad . S ci . U S A 98: 676 – 682.

Ra uch, S. L. , Shin, L. M., Dougherty , D. D., Alpert, N. M., Orr, S. P . ,

L a s ko, M ., M a cklin, M . L . , Fis chma n, A . J . , a nd P it ma n, R . K.

1999. Neural activation during sexual and competitive arousal in

hea lt hy men. Psychiatry Res. Neuroimag. Section 91: 1–10.

R e dou t e , J . , S t o le r u, S . , G r e g oi r e, M ., C o st e s , N ., C i n ot t i , L . ,

L a venne, F. , L e B a rs , D . , Fores t , M . , a nd P u jol, J . 2000. B ra in

p roces s ing of vis u a l s exu a l s t imu li in h u ma n ma les . H u m . B r a i n

M a p p . 11: 162–177.

R e im a n , E . M ., F u s se lm a n , M . J . , F o x, P . T. , a n d R a i ch l e, M . E .

1989a. Neuroana tomical correlat es of an ticipat ory anxiety. Sci ence243: 1071–1074.

Reiman , E. M., Ra ichle, M. E., a nd Robins, E. 1989b. Involvement of

t he t emp ora l p oles in p a t hologia l a nd norma l forms of a nxiet y.

J. Cereb Bl ood F low M etab. 9: S589.

R eima n, E . M . , L a ne, R . D . , Ahern, G . L . , S chwa rt z , G . E . , Da vidson,

R. J ., Frist on, K. J ., Yun, L. S . , an d C hen, K. 1997. Neuroana tomi-

ca l correla t es of ext erna lly a nd int erna lly genera t ed hu ma n emo-

tion. A m . J . P sy ch i a t r y 154: 918 –925.

Rolls, E. T. 1999. T h e B r a i n a n d E m o t i on . Oxford Univ. Press, New

York.

Rolls, E . T. 2000. The orbitofrontal cortex a nd rewa rd. Cereb. Cortex

10: 284 –294.

Royet, J . P., Zald, D., Versace, R., Costes, N., Lavenne, F., Koenig, O.,a nd G erva is , R . 2000. E mot iona l res p ons es t o p lea s a nt a nd u n-



18/18

p lea s a nt olfa ct ory, vis u a l , a nd a u dit ory s t imu li: A p osit ron emis -

sion tomography study. J . N eur osci. 20: 7752–7759.

ozin, P. , a nd Fa llon, A. E. 1987. A perspective on disgust . Psychol.

Rev. 94: 23– 41.

cott , S. K., Young, A. W., Calder, A. J . , Hellawell, D. J . , Aggleton,

J . P . , and J ohnson, M. 1997. Impaired aud itory recognition of fear

a nd a nger following b ila t era l a mygda la r lesions . N a t u r e 385: 254 –

257.

hin, L . M . , Dou ghert y, D. D. , Orr , S. P . , P it ma n, R . K. , L a s ko, M . ,

M a cklin, M . L . , Alp ert , N . M . , Fis chma n, A . J . , a nd R a u ch, S. L .2000. A ct iva t ion of a nt erior p a ra limb ic s t ru ct u res du ring gu ilt -

related script-driven imagery. Biol. Psychiatry 48: 43–50.

imp s on, J . R . , Ongu r, D. , Akb u da k, E . , C ont u ro, T. E . , Ollinger,

J . M., Sn yder, A. Z., G usna rd, D . A., a nd R aichle, M. E. 2000. The

emotional modulation of cognitive processing: An fMRI study. J .

Cogn. Neurosci. 12(S2): 157–170.

mall, D. M., Zald, D. H., J ones-Gotman, M., Zatorre, R. J . , Parado,

J . V . , Frey, S. , a nd P et rides , M . 1999. Hu ma n cort ica l gu s t a t ory

areas: A review of functional neuroimaging data. NeuroReport 10:

7–14.

prengelmeyer, R., Young, A. W., Calder, A. J . , Karnat, A., Lange,

H. W., Homberg, V., Perret, D. I . , and Rowland, D. 1996. Loss of

disgust: Perception of faces and emotions in Huntington ’s disease.

B r a i n 119: 1647–1665.

prengelmeyer, R., Young, A. W., S prengelmeyer, A., C alder, A. J . ,

R owla nd, D . , P erret , D. I . , Homb erg, V. , a nd L a nge, H . W. 1997.

Recognition of facial expressions: S elective impa irment of specifi c

emot ions in Hu nt ingt on ’s dis ea s e. Cogn. Neuropsychol. 14: 839 –

879.

Sprengelmeyer, R., Ra usch, M., Eysel, U. T., and P rzunt ek, H. 1998.

Neural st ructures a ssociat ed wit h recognition of facial expressions

of basic emotions. Proc. R. Soc. Lond. B. Biol. Sci. 265: 1927–31.

St ein, E. A., Pa nkiewicz, J ., Har sch, H. H., Cho, J . K., Fuller, S. A., Hoff-

mann, R. G ., Haw kins, M., Rao, S. M., Bandettini, P. A., and B loom,

A. S . 1998. Nicotine-induced limbic cortical activat ion in the huma n

brain: A functional MRI study. Am. J. Psychiatry 155: 1009 –1015.

Tala ira ch, J ., an d Tournoux, P . 1988. Co-planar Stereotaxic A t las of

t h e H u m a n B r a i n . Thieme Medical, New York.

Tay lor, S . F., Liberzon, I., Fig, L. M., D ecker, L. R., Minoshima, S ., andKoeppe, R. A. 1998. The effect of emotional content on visual recog-

nition memory: A PET activation study. NeuroImage 8: 188 –197.

Tay lor, S. F. , Liberzon, I . , an d Koeppe, R. A. 2000. The effect of

graded aversive stimuli on limbic and visual activation. Neuropsy-

chologia 38: 1415–1425.

Tea s da le, J . D. , Howa rd, R . J . , Cox, S. G . , Ha , Y. , B ra mmer, M . J . ,

Williams, S. C. R., and Checkley, S. A. 1999. Functional MRI study of

the cognitive generat ion of affect. Am . J . Psychiatr y 156: 209 –215.

Weiskrantz, L. 1956. Behavioral changes associated with ablation of

t he a mygda loid comp lex in monkeys . J. Comp. Physiol. Psychol.

49: 381–391.

Wha len, P. J ., Bush, G ., McNally, R. J ., Wilhelm, S., McInerney, S. C.,

J enike, M. A., and R au ch, S. L. 1998a. The emotional counting S troop

paradigm: a functional magnetic resonance imaging probe of theant erior cingulat e a ffective division. Bi ol. Psychi atry 44: 1219–1228.

Wha len, P . J . , R a u ch, S . L . , E t coff , N . L . , M cI nerney, S . C . , L ee,

M. B., and J enike, M. A. 1998b. Masked presentations of emotional

fa cia l expres sions modu la t e a mygda la a ct ivit y w it hou t exp licit

knowledge. J. Neurosci. 18: 411– 418.

48 P H AN E T AL .

1. 3functional neuroanatomy of emotion_ studies in pet and fmri

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