Emotion, Cognition, and Behavior

quietplumIA et Robotique

23 févr. 2014 (il y a 3 années et 7 mois)

281 vue(s)

Science

8 November 2002:

Vol. 298. no. 5596, pp. 1191
-

1194

DOI: 10.1126/science.1076358

Prev

|
Table of Contents

|
Next


REVIEW

NEUROSCIENCE AND PSYCHOLOGY:

Emotion, Cognition, and Behavior

R. J. Dolan

Emotion is central to the qu
ality and range of everyday human experience. The
neurobiological substrates of human emotion

are now attracting increasing
interest within the neurosciences

motivated, to a considerable extent, by
advances in functional

neuroimaging techniques. An emergin
g theme is the
question of

how emotion interacts with and influences other domains of
cognition,

in particular attention, memory, and reasoning. The psychological

consequences and mechanisms underlying the emotional modulation

of
cognition provide the focu
s of this article.


Wellcome Department of Imaging Neuroscience, Institute of Neurology, Queen
Square, London WC1N 3BG, UK. E
-
mail:
r.dolan@fil.ion.ucl.ac.uk



An ability to ascribe value to events in the
world, a product of evolutionary
selective processes, is evident across phylogeny

(
1
). Value in this sense refers
to an organism's facility

to sense whether events in its environment are more or
less desirable.

Within this framework, emotions represent complex
psychological

and physi
ological states that, to a greater or lesser degree,

index
occurrences of value. It follows that the range of emotions

to which an organism
is susceptible will, to a high degree, reflect

on the complexity of its adaptive
niche. In higher order primates,

in

particular humans, this involves adaptive
demands of physical,

socio
-
cultural, and interpersonal contexts.


The importance of emotion to the variety of human experience is evident in that
what we notice and remember is not the mundane

but events that evok
e
feelings of joy, sorrow, pleasure, and pain.

Emotion provides the principal
currency in human relationships

as well as the motivational force for what is
best and worst in

human behavior. Emotion exerts a powerful influence on
reason

and, in ways neither

understood nor systematically researched,

contributes to the fixation of belief. A lack of emotional equilibrium

underpins
most human unhappiness and is a common denominator across

the entire
range of mental disorders from neuroses to psychoses,

as seen,
for example, in
obsessive
-
compulsive disorder (OCD) and

schizophrenia. More than any other
species, we are beneficiaries

and victims of a wealth of emotional experience.


In this article I discuss recent developments in the study of human emotion
where, fo
r example, a neurobiological account

of fear, anger, or disgust is an
increasingly urgent goal. Progress

in emotion research mirrors wider advances
in cognitive neurosciences

where the idea of the brain as an information
processing system

provides a highly

influential metaphor. An observation by the

19th
-
century psychologist, William James, questions the ultimate

utility of a
purely mind
-
based approach to human emotion. James

surmised that "if we
fancy some strong emotion, and then try to

abstract from our
consciousness of it
all the feelings of its

bodily symptoms, we find we have nothing left behind, no
mind
-
stuff

out of which the emotion can be constituted, and that a cold and

neutral state of intellectual perception is all that remains"

(
2
). This quotation
highlights the fact that
emotions

as psychological experiences have unique
qualities, and it is

worth considering what these are. First, unlike most
psychological

states emotions are embodied and manifest in uniquely
recognizable,

and stereotyped, behavioral patterns of facial exp
ression,
comportment,

and autonomic arousal. Second, they are less susceptible to our

intentions than other psychological states insofar as they are

often triggered, in
the words of James, "in advance of, and often

in direct opposition of our
deliberate re
ason concerning them"

(
2
). F
inally, and most importantly, emotions
are less

encapsulated than other psychological states as evident in their

global
effects on virtually all aspects of cognition. This is

exemplified in the fact that
when we are sad the world seems less

bright, we stru
ggle to concentrate, and
we become selective in

what we recall. These latter aspects of emotion and
their influences

on other psychological functions are addressed here.


EMOTION, PERCEPTION,

AND ATTENTION

An evolutionary perspective on emotion suggests th
at environmental events of
value should be susceptible to preferential perceptual

processing. One means
of achieving this is by emotion enhancing

attention, leading to increased
detection of emotional events.

The influence of emotion on attention can be
st
udied in classic

visual search and spatial orienting tasks. In a visual search,

the standard finding is that the time taken to detect a specified

target increases
in direct proportion to the number of irrelevant

distracters, indicating serial
attentive pro
cessing. However,

for emotional stimuli there is more rapid target
detection for

faces with positive or negative expressions, or for spiders or

snakes, with the most consistent capture of attention being evident

for fear
-
relevant stimuli (
3
). Similar effects are seen

in spatial orien
ting tasks where
there is a faster response to

targets appearing on the same side as an
emotional cue (e.g.,

faces, spiders, threat words, conditioned shapes) and a
slower

response to those appearing on the opposite side (
4
,

5
). Neuroimaging
data, using spatial orienting paradigms,

point to orbital prefrontal c
ortex as a
possible site of interaction

(
4
).

The "capture of attention" is not the sole means by which emotional stimuli
influence perception, and emerging evidence indicates

mechanisms
independent of attention. Perceptual processing under

conditions of limited
attention as, for exa
mple, processing of

stimuli at unattended spatial locations is
often referred to as

preattentive. In visual backward masking paradigms, a
briefly

presented (ms) target can be rendered invisible if immediately

followed by
a second "masking stimulus." In sit
uations where the

hidden target stimulus is
an emotional item, for example a conditioned

angry face or a spider, preserved
processing can be indexed by

differential skin conductance responses (SCRs)
to fear
-
relevant

compared with fear
-
irrelevant targets, e
ven though the target

stimulus is not perceived (
6
). Similar findings are evident

using the attentional
blink paradigm. This refers to a situation

where detection of an initial target
stimulus in a visual stimulus

stream leads to impaired awareness, or
"inattentional blindness,"

for
a successive second target. This inattentional
blindness is

greatly diminished where a second target is an emotional item

(
7
).
This finding suggests an advantage in detection

of an emotional item even in
circumstances where attentional resources

are limited.

Studies of patients with

focal brain lesions provide additional evidence for
independence of emotional processing from attentional

mechanisms. After brain
damage to right inferior parietal cortex,

patients frequently fail to perceive a
stimulus presented in their

contralesional h
emifield (spatial neglect) or, in milder
forms,

fail to perceive a stimulus when a simultaneous stimulus is presented

on
the ipsilesional side (sensory extinction). This contralesional

deficit is greatly
attenuated for emotional stimuli, such as faces

with

happy or angry expressions
(
8
) or images of spiders

(
9
)
. Noncon scious processing of emotion has also
been

demonstrated in the blindfield of patients with damage to primary

visual
cortex (
10
). These findings indicate processing

of emotional stimuli occurs
before the operation of selective

attention and such "preattentive processing"
re
sults in enhanced

stimulus detection.

Pre
-
attentive processing of emotional stimuli, such as faces, implies an early
discrimination between the occurrence of emotional

and nonemotional events.
Using magneto
-
encephalography (MEG),

discriminatory responses
to emotional
faces are seen in midline

occipital cortex as early as 100

to 120

ms after
stimulus onset,

before the onset of a characteristic face
-
related response at

approximately 170

ms (
11
,
12
). Intermodal

binding of emotion for presentation
of anger in voice and face

is associated with a distinct electro
encephalographic
potential

occurring at about 100

ms (
13
). Short
-
latency responses

(120

to
160

ms) to aversive stimulus presentation are also seen

during direct
intracerebral recordings within ventral prefrontal

cortex (
14
). Thus,
electrophysiological data point to

rapid and widespread neuronal responses to

emotional stimuli that

precede responses associated with actual stimulus
identification

which occur at approximately 170

ms after stimulus onset.


An important neurobiological question is how processing of emotional stimuli
proceeds in the absence of atte
ntion. Accumulating

evidence points to the
amygdala as an important mediator of emotional

influences on perception (
Fig.
1
). In functional neuroimaging

experiments using visual backward masking
paradigms, where emotional

stimuli are presented out of awareness, an
amygdala response di
scriminates

between unseen emotional and unseen
nonemotional targets (
15
,

16
). In other experiments with overt stimulus
presentation

but where attention is systematically manipulated, an amygdala

response to fearful faces is independent of the concurrent focus

of attention
(
17
). Studies involving patients with either

blindsight or v
isual extinction
demonstrate an amygdala response

to emotional stimuli presented out of
awareness in the damaged

hemifield (
18
,
19
). Residual processing abilities

for
unaware emotional stimulus presentation are associated with

engagement of a
subcortical retino
-
collicular
-
pulvinar pathway

specific to unawar
e emotional
stimulus processing (
15
,

18
). The involv
ement of this pathway is of considerable

interest, because it is also implicated in residual visual processing

evident in
patients with blindsight. One suggestion is that certain

classes of emotional
stimuli, for example coarse visual cues present

in fearf
ul faces, can be
processed by a noncortical pathway to

enable rapid adaptive responses to
danger (
20
).


Fig. 1.

An emotional
-
perceptual
-
memory circuit in the human
brain. The amygdala (red), an anterior
medial temporal lobe
structure, is a crucial structure in registering emotional
occurrences. Extensive connection (arrows) to visual cortex
(orange) and hippocampus (blue) allows amygdala to modulate their function
and facilitate perceptual and memory func
tions in those regions.
[View Larger
Version of this Image (70K GIF file)]




A related neurobiological question is how preattentive processing of emotional
events influences, and

indeed enhances, perception.

One possibility is that
inputs from emotional processing regions,

in particular the amygdala, modulate
the function of regions involved

in early object perceptual processing.
Anatomically, the amygdala

receives visual inputs f
rom ventral visual pathways
and sends

feedback projections to all processing stages within this pathway

(
21
). Neuroimaging data provide evidence for context
-
dependent

enhancement
of functional connectivity between amygdala and extrastriate

visual regions
expressed during processing

of an emotional visual

input (
22
,
23
). There is now

evidence showing

this connectivity has psychological consequences in that after

amygdala damage a visual perceptual enhancement for emotional

items is
abolished (
7
).


EMOTION, MEMORY, AND

LEARNING

Privileged perceptual processing of emotional events provide a means of not
only index
ing occurrences of value but facilitating

their availability to other
cognitive domains. The cognitive domain

where the influence of emotion is best
understood is memory. Enhanced

memory for events of value allow better
predictions regarding

biologically i
mportant occurrences when re
-
encountering
similar

events in the future. The best example is seen in classical conditioning,

which provides an inflexible, ubiquitously expressed form of emotional

memory.
In simple terms, this form of memory describes a situ
ation

where a neutral
stimulus, through pairing in temporal contiguity

with an emotional stimulus (for
example, an aversive noise in

fear conditioning), acquires an ability to predict
future occurrences

of this emotional event. From a human behavioral
pers
pective,

the importance of this form of memory is that it provides a potential

link between a psychological mechanism and psychopathological

conditions,
such as phobias and post
-
traumatic stress disorder

(PTSD).

Studies demonstrate that human amygdala is
critical for fear conditioning, a
form of implicit memory. Patients with amygdala

damage do not acquire
conditioned fear responses despite retaining

explicit knowledge regarding the
conditioned (CS) and unconditioned

stimulus (UCS) associations (
24
). In
contrast, patients

with hipp
ocampal damage and intact amygdala preserve fear
conditioning

despite being unable to demonstrate explicit knowledge regarding

CS
-
UCS contingencies (
25
). Functional neuroimaging experiments

also confirm
the importance of the amygdala for learning of CS
-
UCS

associations but point to

a time
-
limited role for this structure

(
26
,
27
). Ev
idence that the role of the
amygdala

during emotional learning may be time
-
limited could indicate that

more enduring memory effects are expressed elsewhere in the brain.

Although
there is an emphasis on the role of the amygdala in human

fear conditioning
s
tudies, evidence indicates that it supports

other forms of associative learning,
including reward and appetitive

learning (
28
,
29
).


Enhanced autobiographical or explicit memory for emotional events is well
documented in anecdotal accounts of enhanced recollection

for events such as
the assassination of Pre
sident Kennedy or the

Challenger shuttle disaster. The
benefit of emotion on episodic

memory function is confirmed in numerous
studies showing mnemonic

enhancement for material that encompasses
personal autobiographical,

picture
-
, and word
-
based items (
30
,
31
), an

effect
most pronounced in free recall tasks
. An enhanced memory

for emotional items
is also reported in amnesiacs, who despite

profound deficits in episodic memory
show normal memory enhancement

for emotional material when tested by
recognition (
32
).


A striking feature of the biology of emotional memory is a dependence on
the
amygdala that transcends the implicit
-
explicit

distinction. Thus, patients with
bilateral amygdala damage do

not show an advantage in subsequent recall of
emotional items

and events (
33
,
34
). The critical role of

the amygdala is also
evidenced by functional neuroimaging experiments

where engagement of t
he
amygdala during encoding predicts later

recall of emotional material (
35
,
36
).
Crucially,

enhanced amygdala activity to both positive and negative stimuli

is
predictive of later memory (
31
). The role of the

amygdala in episodic memory
extends beyond encoding processes,

as evidenced by the fact that this structure
is also engaged
during

retrieval of emotional items and contexts (
37
,
38
).


The neurochemical mechanisms by which emotional events augment memory
have been extensively studied in animal experiments

that provide evidence of a
-
adrenergic

modulation (
39
).

Emotiona
l memory enhancement in human
subjects can be blocked

by administration of the
-
adrenoreceptor blocker
propranolol

before study (
40
). This blockade is equivalent to that

seen after
human amygdal
a damage, providing indirect evidence

that the amygdala might
be a critical locus for propranolol's

effects.

The fact that amygdala is engaged during episodic recall for emotional material
suggests a role beyond providing a neuromodulatory

signal to extra
-
amygdala
structures at encoding. Psychological

evidence that emotion influences episodic
memory function indicates

influences on hippocampal function and most
probably extra
-
amygdala

regions. Learning
-
related plastic changes have been
extensively

describe
d in animal studies of emotion as, for example, the
experience
-
dependent

retuning of sensory cortices after conditioning (
41
).

These plastic changes may also be important in the expression

of emotional
memory in humans. For example, auditory cortex plasticity

during fear
conditioni
ng to tones can be demonstrated with neuroimaging

while
administration of the central muscaranic receptor blocker

scopolamine, before
conditioning, blocks its expression (
42
).

This finding is consistent with animal
studies, implicating amygdala

influences on cholinergic neurotransm
ission in the
establishment

of enduring memory traces (
41
).


EMOTION AND SUBJECTI
VE FEELING STATES

One problem that confronts human emotion research is a conflation of
mechanisms indexing the occurrence of an emotional event,

which may include
automatic response repertoires, referr
ed to

as emotion, and their subjective or
experiential counterparts,

referred to as feelings (
43
,
44
). Feelings

are defined
as mental representations of physiological changes

that characterize and are
consequent upon processing emotion
-
eliciting

objects or states. In more
extended form, the suggestion is th
at

patterned neural responses provide for a
differentiation of feeling

states, this account assigns an important causal role to
afferent

feedback, sensory and neurochemical, to the brain regarding emotion
-
induced

changes in body state. The importance of af
ferent feedback in

the
experience of emotion is supported by phenomenological evidence

from
patients with a rare acquired failure of peripheral autonomic

regulation, pure
autonomic failure (PAF), who have subtle blunting

of emotional experience.
However, t
he role of feeling states extends

beyond providing subjective coloring
to experience, and it is

proposed that feelings influence functions such as
decision making

and interpersonal interactions (
43
).


A consequence of the fractionation of emotion and feelings implies the following
functional arrangement. Perception of emotional

events leads to rapid,
automatic, and stereotyped emotional responses

that contrasts with more long
-
term modulatory behavioral influences

mediated by feeling states. If this general
scheme is correct,

then it

is expected that brain systems supporting emotional
perception

and execution should be distinct from those supporting feeling

states.
It has been proposed that structures mediating feeling

states are those that
receive inputs regarding the internal milieu
,

viscera and musculoskeletal
structures and include the brain stem

tegmentum, hypothalamus, insula, and
somatosensory and cingulate

cortices (
43
).

There is now accumulating evidence that emotion and feeling are mediated by
distinct neuronal systems. Functional neuroimaging

experi
ments indicate that
the generation and representation of

peripheral autonomic states involve many
of the predicted structures,

particularly anterior cingulate and insular
-
somatosensory cortices

(
45
-
47
) (
Fig. 2
). More specifically,

recall of subjective
feeling states associated with past emotional

experiences
engages regions
encompassing upper brainstem nuclei,

hypothalamus, somatosensory, insula
and orbitofrontal cortices

(
48
). In subjects with PAF, absence of visceral afferent

information regarding the peripheral body state attenuates emotion

and effort
-
related activity in similar reg
ions (
49
,

50
). A notable feature of these studies is

an absence

of amygdala engagement, a critical structure in emotional
perception.

Indeed a study of patients with unilateral and bilateral amygdala

lesions indicates that they experience no deficit in their phenomenal

experience
of emotion (
51
). The implication is that

there is a s
egregation within emotion
-
processing regions between

those mediating perceptual
-
mnemonic and
experiential effects.



Fig. 2.

Brain regions implicated in emotional experience incl
ude orbitofrontal
cortex (yellow), insular cortex (purple), and anterior (blue) and posterior (green)
cingulate cortices. The amygdala (red) is involved in linking perception with
automatic emotional responses and memory.
[View Larger Version of this
Image (45K GIF file)]




EMOTION AND DECISION
-
MAKING

Within philosophy there is a long tradition that views emotion and reason in
direct opposition. Such an oppositional relation

has b
een questioned on the
basis that, under certain circumstances,

emotion
-
related processes can
advantageously bias judgment and

reason. This biasing effect appears to reflect
influences of perceptual

emotional mechanisms on the one hand and feeling
states on

the

other. In terms of the former, neuropsychology and functional

neuroimaging evidence indicate that the amygdala contributes to

perceptual
value judgments as, for example, making trustworthy

decisions in relation to the
facial appearance of others (
52
,

53
). In terms of the latter, psychological data
poin
t

to subtle influences of body states on decision making. For example,

in
masked presentation of either fear
-
conditioned or non
-
conditioned

stimuli,
subjects show differential shock expectancy ratings on

shock versus no
-
shock
trials despite their lack of a
wareness of

shock
-
predictive stimuli (
54
). Individuals
who are able

to detect their heartbeat on a heartbeat detection task, an index

of
visceral awareness, have enhanced performance predicting the

likely
occurrence of a shock in these same paradigms (
55
).

The inference here is that
better predictive judgme
nts are mediated

via an enhanced awareness of bodily
states of arousal.


The volitional control of behavior is dependent on the functions of prefrontal
cortex, particularly its dorsolateral and dorsomedial

sectors. An emotional
contribution to high
-
level d
ecision making

is evident after ventromedial
prefrontal cortex damage, which

may have no consequence for intellectual
function but results

in patients making personally disadvantageous decisions
(
56
).

The proposal is that these subjects fail to evoke appropriate

feeling states
asso
ciated with the contemplation of possible scenarios

which constitute options
for action. As formulated in the somatic

marker hypothesis, this region provides
access to feeling states

in relation to past decisions during contemplation of
future decisions

of

a similar nature (
44
). Th
us, evocation of past feeling

states
biases the decision
-
making process, toward or away from

a particular
behavioral option. Empirical support for the theory

includes evidence that
patients with lesions to ventromedial prefrontal

cortex fail to generate th
e normal
anticipatory SCR responses

in tasks where they ponder potentially risky choices
(
57
).

In addition, neuroimaging and neuropsycholgical evidence indicate

that this
region is activated during anticipatory states (
46
,

58
) and by outcomes
associated with reward or punishment

(
59
). The functions of this region may
also extend beyond

this to include a role

in regulating interpersonal interactions

by providing the basis for what the philosopher Suzanne Langer

described as
the "involuntary breach of selfhood" that constitutes

empathic experience. A lack
of capacity for empathy may account

for behavioral defic
its of a sociopathic
nature seen in subjects

with acquired ventromedial prefrontal damage (
60
,
61
).


CONCLUSIONS

A growing interest in the neurobiology of emotion parallels a wider recognition
of its importance to human experience and

behavior. The broad outlines of brain
structures that mediate

emotion and

feelings are now reasonably clear and
include brainstem

autoregulatory systems; amygdala, insula, and other
somatosensory

cortices; cingulate and orbital
-
prefrontal cortices. Within this

set
of brain regions there is variable contribution to perceptual,

m
nemonic,
behavioral, and experiential aspects of emotion. Despite

progress in defining a
functional anatomy of emotion, we still

have little idea how emotion relates to
other major axes of affective

experience represented by motivation and mood.
This is an

issue

that is critical to a deep understanding of many psychiatric
disorders.

For example, patients with mood disorders display dysfunction

in
similar brain regions to those that mediate emotion, yet at

a psychological level
the nature of the relation is
far from clear

(
62
,
63
). Furthermore, how
neurochemi
cal control

systems modulate affective states, including emotional
states,

is largely unknown. There is also the perplexing issue of how

emotion
infects rational thought processes such that people adhere,

often with great
conviction, to ideas and beliefs t
hat have no

basis in reason or reality. Lastly,
there is an urgent need to

examine the role of emotion in cognitive development
and, in particular,

to address how the growth of emotional awareness informs
mechanisms

that underwrite the emergence of self
-
id
entity and social
competence.


REFERENCES AND NOTES

1.

K. J. Friston,
et al
.,
Neuroscience

59
, 229 (1994)
[CrossRef]

[ISI]

[Medline]
.

2.

W. James,
The Principles of Psychology

(Holt, New York, 1890).

3.

A
. Ohman,
et al
.,
J. Exp. Psychol. Gen.

130
, 466 (2001)
[CrossRef]

[ISI]

[Medline]
.

4.

J. L. Armony,
et al
.,
Neuropsychologia

40
, 817 (2002)
[CrossRef]

[ISI]

[Medline]
.

5.

K. Mogg,
et al
.,
Behav. Res. Ther.

35
, 297 (1997)
[CrossRef]

[ISI]

[Medline]
.

6.

F. Esteves,
et al
.,
Psychophysiology

31
, 375 (1994)
[ISI]

[Medline]
.

7.

A. K. Anderson and E. A. Phelps,
Nature

411
, 305 (2001)
[CrossRef]

[ISI]

[Medline]
.

8.

P. Vuilleumier,
et al
.,
Neurology

56
, 153 (2001)
[Abstract/
Free

Full

Text]
.

9.

___,
Neuroreport
12
, 1119.

(2001).

10.

B.

de Gelder,
et al
.,
Neuroreport

10
, 3759 (1999)
[ISI]

[Medline]
.

11.

E. Halgren
et al.
,
Cereb. Cortex
10
, 69

( 2000).

12.

M. Eimer and A. Holmes,
Neuroreport

13
, 427 (2002)
[CrossRef]

[ISI]

[Medline]
.

13.

G. Pourtois,
et al
.,
Neuroreprort

11
, 1329 (2000) .

14.

H. Kawasaki,
et al
.,
Nature Neurosci.

4
, 15 (2001)
[CrossRef]

[ISI]

[Medline]
.

15.

J. S. Morris,
et al
.,
Nature

393
, 467 (1998)
[CrossRef]

[ISI]

[Medline]
.

16.

P. J. Whalen,
et al
.,
J.

Neurosci.

18
, 411 (1998)
[Abstract/
Free

Full

Text]
.

17.

P. Vuilleumier,
et al
.,
Neuron

30
, 829 (2001)
[CrossRef]

[ISI]

[Medline]
.

18.

J. S. Morris,
et al
.,
Brain

124
, 1241 (2001)
[Abstract/
Free

Full

Text]
.

19.

P. Vuilleumier,
et al
.,
Neuropsychologia

40
,

2156 (2002)
[CrossRef]

[ISI]

[Medline]
.

20.

J. LeDoux,
The Emotional Brain

(Weidenfeld &

Nicholson, London, 1998).

21.

D. G.

Amaral, J.

L.

Price, A.

Pitkanen, S.

T.

Carmichael, in
The Amygdala:
Neurobi
ological Aspects of Emotion, Memory and Mental Dysfunction,

J.

Aggleton, Ed. (Wiley
-
Liss, New York, 1992).

22.

J. S. Morris,
et al
.,
Brain

121
, 47 (1998)
[
Abstract/
Free

Full

Text]
.

23.

P. Rotshtein,
et al
.,
Neuron

32
, 747 (2001)
[CrossRef]

[ISI]

[Medline]
.

24.

K. S. LaBar,
et al
.,
J Neurosci

15
, 6846 (1995)
[Abstract/
Free

Full

Text]
.

25.

A. Bechara,
et al
.,
Science

269
, 1115 (1995)
[Abstract/
Free

Full

Te
xt]
.

26.

C. Buchel,
et al
.,
Neuron

20
, 947 (1998)
[CrossRef]

[ISI]

[Medline]
.

27.

K. S. LaBar,
et al
.,
Neuron

20
, 937 (1998)
[CrossRef]

[ISI]

[Medline]
.

28.

I. S. Johnsrude,
et al
.,
J Neurosci

20
, 2649 (2000)
[Abstract/
Free

Full

Text]
.

29.

J. O'Doherty,
et al
.,
Neuron

33
, 815 (2002)
[CrossRef]

[ISI]

[Medline]
.

30.

E. A. Phelps,
et al
.,
Brain Cogn.

35
, 85 (1997)
[CrossRef]

[ISI]

[Medline]
.

31.

S. B. Hamann,
et al
.,
Nature Neurosci.

2
, 289 (1999)
[CrossRef]

[ISI]

[Medline]
.

32.

S. B. Hamann,
et al
.,
Learn. Mem.

4
, 301 (1997)
[Abstract]
.

33.

R. Babinsky,
et al
.,
Behav. Neurobiol.

6
, 167 (1993) .

34.

R. Adolphs,
et al
.,
Learn. Mem.

4
, 291 (1997)
[Abstract]
.

35.

L. Cahill,
et al
.,
Proc. Natl. Acad. Sci. U.S.A.

93
, 8016 (1996)
[Abstract/
Free

Full

Text]
.

36.

R T. Canli,
et al
.,
J. Neurosci.

20
, C99 (2000) .

37.

E. J. Maratos,
et al
.,
Neuropsychologia

39
, 910 (2001)
[CrossRef]

[ISI]

[Medline]
.

38.

R. J. Dolan,
et al
.,
Neuroimage

11
, 203 (2000)
[CrossRef]

[ISI]

[Medline]
.

39.

J. L. McGaugh,
Science

287
, 248 (2000)
[Abstract/
Free

Full

Text]
.

40.

L. Cahill,
et al
.,
Nature

371
, 702 (1994)
[Cross
Ref]

[ISI]

[Medline]
.

41.

N. M. Weinberger,
Neurobiol. Learn.
Mem.

70
, 226 (1998)
[CrossRef]

[ISI]

[Medline]
.

42.

C. Theil, K. J. Friston, R. J. Dolan,
Neuron

35
, 567 (2002)
[CrossRef]

[ISI]

[Medline]
.

43.

A. Damasio,
The
Feeling of What Happens

(Harcourt Brace, New York,
1999).

44.

A. R.

Damasio,
Descartes' Error

(Picador, London, 1995).

45.

H. D. Critchley,
et al
.,
Brain

124
, 1003 (2001)
[Abstract/
Free

Full

Text]
.

46.

H. D. Critchley,
et al
.,
Neuron

29
, 537 (2001)
[CrossRef]

[ISI]

[Medline]
.

47.

H. D. Critchley,
et al
.,
J. Neurosci.

20
, 3033 (2000)
[Abstract/
Free

Full

Text]
.

48.

A. R. Damasio,
et al
.,
Nature Neurosci.

3
, 1049 (2000)
[CrossRef]

[ISI]

[Medline]
.

49.

H. D. Critchley,
et al
.,
Nature Neurosci.

4
, 207 (2001)
[CrossRef]

[ISI]

[Medline]
.

50.

___,
Neuron

33
, 653 (2002)
[CrossRef
]

[ISI]

[Medline]
.

51.

A. K. Anderson,
et al
.,
J. Cogn. Neuro
sci.

14
, 70 (2002)
[Abstract/
Free

Full

Text]
.

52.

R. Adolphs,
et al
.,
Nature

393
, 470 (1998)
[CrossRef]

[ISI]

[Medline]
.

5
3.

J. S. Winston,
et al
.,
Nature Neurosci.

5
, 277 (2002)
[CrossRef]

[ISI]

[Medline]
.

54.

A. Ohman,
et al
.,
J. Exp. Psychol. Gen.

127
, 69 (1998)
[CrossRef]

[ISI]

[Medline]
.

55.

E. S. Katkin,
et al
.,
Psychol. Sci.

12
, 366 (2001)
[CrossRef]

[ISI]

[Medline]
.

56.

A. Bechara,
et al
.,
Cereb. Cortex

10
, 295 (2000)
[Abstract/
Free

Full

Text]
.

57.

A. Bechara,
et al
.,
Brain

123
, 2189 (2000)
[Abstract/
Free

Full

Text]
.

58.

A. Bechara,
et al
.,

Science

275
, 1293 (1997)
[Abstract/
Free

Full

Text]
.

59.

R. D. Rogers,
et al
.,
J. Neurosci.

19
, 9029 (1999)
[Abstract/
Free

Full

Text]
.

60.

S. W. Anderson,
et al
.,
Nature Neurosci.

2
, 1032 (1999)
[CrossRef]

[ISI]

[Medline]
.

61.

R. J. Davidson,
et al
.,
Science

289
, 591
(2000)
[Abstract/
Free

Full

Text]
.

62.

H. S. Mayberg,
et al
.,
Biol. Psych.

48
, 830 (2000)
[CrossRef]

[ISI]

[Medline]
.

63.

W. C. Drevets,
Progr. Brain Res.

126
, 413 (2000)
[ISI]

[Medline]
.

64.

R. J.

D.

is supported by a Wellcome Trust Programme Grant.


10.1126/science.1076358

Include this information when citing this paper.




THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:

Chronic Pain and the Emotional Brain: Spe
cific Brain Activity Associated with Spontaneous
Fluctuations of Intensity of Chronic Back Pain.

M. N. Baliki, D. R. Chialvo, P. Y. Geha, R. M. Levy, R. N. Harden, T. B. Parrish, and A. V.
Apkarian (2006)

J. Neurosci.
26
, 12165
-
12173




Abstract »




Full Text »




PDF »


Imitating expressions: emotion
-
specific neural substrates in facial mimicry.

T.
-
W. Lee, O. Josephs, R. J. Dolan, and H. D. Critchley (2006)

Soc Cogn Affect Neurosci

1
, 122
-
135




Abstract »




Full Text »




PDF »


The locus ceruleus is involved in the successful retrieval of emotional memories in humans..

V. Sterpenich, A. D'Argembeau, M
. Desseilles, E. Balteau, G. Albouy, G. Vandewalle, C.
Degueldre, A. Luxen, F. Collette, and P. Maquet (2006)

J. Neurosci.
26
, 7416
-
7423




Ab
stract »




Full Text »




PDF »


The neural

basis of interindividual variability in inhibitory efficiency after sleep deprivation..

Y. M. L. Chuah, V. Venkatraman, D. F. Dinges, and M. W. L. Chee (2006)

J. Neurosci.
26
, 7156
-
7162




Abstract »




Full Text »




PDF »


Contrasting Effects of Reward Expectation on Sensory and Motor Memories in Primate Prefrontal
Neurons.

K.
-
i. Amemori and T. Sawaguchi (2006)

Cereb Cortex
16
, 1002
-
1015




Abstract »




Full Text »




PDF »


The mellow years?: neural basis of improving emotional stability over age..

L. M. Williams, K. J. Brown, D. Palmer, B. J. Liddell, A. H. Kemp, G. Olivieri, A. Peduto, and
E.
Gordon (2006)

J. Neurosci.
26
, 6422
-
6430




Abstract »




Full Text »




PDF »


Fear recognition ability predicts differences in social cognitive and neural functioning in men..

B. C
orden, H. D. Critchley, D. Skuse, and R. J. Dolan (2006)

J. Cogn. Neurosci.
18
, 889
-
897




Abstract »




Full Text »




PDF »


Retinoic acid signaling in the functioning brain..

U. C. Drager
(2006)

Sci. STKE
2006
, pe10




Abstract »




Full Text »




PDF »


Maternal depressive symptoms, relationship satisfaction, and verbal behavior: A social
-
cognitive
analysi
s.

S. A. Tenzer, D. W. Murray, C. A. Vaughan, and W. P. Sacco (2006)

Journal of Social and Personal Relationships
23
, 131
-
149




Abstract »




PDF »


Perfusion functional MRI reveals cerebral blood flow pattern under psychological stress.

J. Wang, H. Rao, G. S. Wetmore, P. M. Furlan, M. Korczykowski, D
. F. Dinges, and J. A. Detre
(2005)

PNAS
102
, 17804
-
17809




Abstract »




Full Text »




PDF »


Neuroanatomical correlates of behavioural disorders in dementia.

H. J. Rosen, S. C. Allison, G. F
. Schauer, M. L. Gorno
-
Tempini, M. W. Weiner, and B. L. Miller
(2005)

Brain
128
, 2612
-
2625




Abstract »




Full Text »




PDF »


Regulation of synaptic plasticit
y in a schizophrenia model.

B. Gisabella, V. Y. Bolshakov, and F. M. Benes (2005)

PNAS
102
, 13301
-
13306




Abstract »




Full Text »




PDF »


Kindling
-
induced changes in plasticity of the rat a
mygdala and hippocampus.

M. Schubert, H. Siegmund, H.
-
C. Pape, and D. Albrecht (2005)

Learn. Mem.
12
, 520
-
526




Abstract »




Full Text »




PDF »


Noradrenergic Modulation of Emotion
-
Induced F
orgetting and Remembering.

R. Hurlemann, B. Hawellek, A. Matusch, H. Kolsch, H. Wollersen, B. Madea, K. Vogeley, W.
Maier, and R. J. Dolan (2005)

J. Neurosci.
25
, 6343
-
6349




Abstract »




Full Text »




PDF »


Emotional and Temporal Aspects of Situation Model Processing during Text Comprehension: An
Event
-
Related fMRI Study.

E. C. Ferstl, M. Rinck, and D. Y. von Cramon (2005)

J. Cogn. Neurosci.
17
, 724
-
739




Abstract »




Full Text »




PDF »


Behavioral and Electrophysiological Evidence of a Right Hemisphere Bias for the Influence of
Negative Emotion on Higher Cognition.

E. R. Simon
-
Thomas, K. O. Role, and R. T. Knight
(2005)

J. Cogn. Neurosci.
17
, 518
-
529




Abstract »




Full Text »




PDF »


Attention Bias to Threat in Maltreated Children: Implications for Vulnerability to Stress
-
Related
Psychopathology.

D. S. Pine, K. Mogg, B. P. Bradley, L. Montgomery, C. S. Monk, E. McClure, A. E. Guyer, M.
Ernst, D. S. Charney, and J. Kaufman (2005)

Am J Psychiatry
162
, 291
-
296




Abstract »




Full Text »




PDF »


Recognition Memory for Emotional and Neutral Faces: An Event
-
Related Potential Study.

M. Johansson, A. Mecklinger, and A.
-
C. Treese (2004)

J. Cogn. Neurosci.
16
, 1840
-
1853




Abstract »




Full Text »




PDF »


fMRI
-
Adaptation Reveals Dissociable Neural Representations of Identity and Expression in Face
Perception.

J. S. Winston, R.N.A. Henson, M. R. Fine
-
Goulden, and R. J. Dolan (2004)

J Neurophysiol

92
, 1830
-
1839




Abstract »




F
ull Text »




PDF »


Psychobiological Mechanisms of Resilience and Vulnerability: Implications for Successful
Adaptation to Extreme Stress.

D. S. Charney (
2004)

Focus
2
, 368
-
391




Abstract »




Full Text »




PDF »


Brain Mechanisms for Inferring Deceit in the Actions of Others.

J. Grezes, C. Frith, and R. E. Passingham

(2004)

J. Neurosci.
24
, 5500
-
5505




Abstract »




Full Text »




PDF »


The Involvement of the Orbitofrontal Cortex in the Experience of Regret.

N. Camille, G. Coricelli, J. Sallet, P
. Pradat
-
Diehl, J.
-
R. Duhamel, and A. Sirigu (2004)

Science
304
, 1167
-
1170




Abstract »




Full Text »




PDF »


Two routes to emotional memory: Distinct neural processes fo
r valence and arousal.

E. A. Kensinger and S. Corkin (2004)

PNAS
101
, 3310
-
3315




Abstract »




Full Text »




PDF »


Psychobiological Mechanisms of Resilience and Vulnerability: Implications for Suc
cessful
Adaptation to Extreme Stress.

D. S. Charney (2004)

Am J Psychiatry
161
, 195
-
216




Abstract »




Full Text »




PDF »


Nonhuman Primate Models to Study Anxiety
, Emotion Regulation, and Psychopathology.

N. H. KALIN and S. E. SHELTONA (2003)

Ann. N.Y. Acad. Sci.
1008
, 189
-
200




Abstract »




Full Text »




PDF »


A modulatory role for facia
l expressions in prosopagnosia.

B. de Gelder, I. Frissen, J. Barton, and N. Hadjikhani (2003)

PNAS
100
, 13105
-
13110




Abstract »




Full Text »




PDF »


Gambling Urges in Pathological Gambling
: A Functional Magnetic Resonance Imaging Study.

M. N. Potenza, M. A. Steinberg, P. Skudlarski, R. K. Fulbright, C. M. Lacadie, M. K. Wilber, B. J.
Rounsaville, J. C. Gore, and B. E. Wexler (2003)

Arch Gen Psychiatry
60
, 828
-
836




Abstract »




Full Text »




PDF »


Will the Genomics Revolution Revolutionize Psychiatry?.

K. R. Merikangas and N. Risch (2003)

Am J Psychiatry
160
, 625
-
635




Full Text »




PDF »




The Journal of Neuroscience, January 1, 1998, 18(
1):411
-
418

Masked Presentations of Emotional Facial Expressions Modulate Amygdala
Activity without Explicit Knowledge

Paul J. Whalen, Scott L. Rauch, Nancy L. Etcoff, Sean C. McInerney, Michael B.
Lee, and Michael A. Jenike

Psychiatric Neuroimaging Resea
rch Group and Nuclear Magnetic Resonance Center, Massachusetts General Hospital
and Harvard Medical School, Boston, MA 02115




ABSTRACT

Functional magnetic resonance ima
ging (fMRI) of the human brain was used to study whether the amygdala is
activated in response

to emotional stimuli, even in the absence of explicit knowledge

that such stimuli were presented.
Pictures of human faces bearing

fearful or happy expressions we
re presented to 10

normal, healthy

subjects by using a
backward masking procedure that resulted in

8

of 10

subjects reporting that they had not seen these facial

expressions.
The backward masking procedure consisted of 33

msec

presentations of fearful or h
appy facial expressions, their
offset

coincident with the onset of 167

msec presentations of neutral

facial expressions. Although subjects reported
seeing only neutral

faces, blood oxygen level
-
dependent (BOLD) fMRI signal in the

amygdala was significantly

higher during viewing of masked fearful

faces than during the viewing of masked happy faces. This difference

was
composed of significant signal increases in the amygdala to

masked fearful faces as well as significant signal
decreases to

masked happy faces
, consistent with the notion that the level

of amygdala activation is affected
differentially by the emotional

valence of external stimuli. In addition, these facial expressions

activated the
sublenticular substantia innominata (SI), where

signal increases

were observed to both fearful and happy faces
suggesting

a spatial dissociation of territories that respond to emotional

valence versus salience or arousal value.
This
study, using fMRI

in conjunction with masked stimulus presentations, represents

an initial step toward determining
the role of the amygdala in

nonconscious processing.

Key words: amygdala; extended amygdala; substantia innominata; nucleus basalis of
Meynert; bed nucleus of the
stria terminalis; emotion; facial expression; backward masking; awareness; fMRI; neuroimaging




INTRODUCTION

Neuroscientific research provides many e
xamples of tasks executed below the level of awareness (Schacter et al.,
1993
; He

et al., 1996
; Berns et al., 1997
; Rauch et al., 1
997
). It has

been argued that initial respo
nses to
affective stimuli are automatic

and do not require awareness (Zajonc, 1980
). The amygdala is a

brain area located
within the medial temporal lobe that is known

to process affective or emotionally valenced stimuli (see Aggleton,

1992
). On the basis, in part, of animal studies demonstrating

a direct short
-
latency pathway from the thalam
us to the
amygdala

(LeDoux et al., 1985
), L
eDoux (1996)

has proposed that the amygdala

might survey emotionally
valenced stimuli without awareness. Consistent

with this notion, studies of human subjects by Öhman and colleagues

(Öhman, 1992
) have demonstrated skin conductance responses to

emotionally valenced facial expressions
conditioned to predict

an aversive electrical shock when

these expressions were presented

in a manner that prevented
awareness (i.e., backward masking).

Taking a lead from human lesion data (Adolphs et al., 1995
; Calder

et al.,
1996
), recent neuroimaging reports in humans have demonstrated

activation within the amygdala in response to
facial expressions

of emotion (Breiter et al., 1996
; Morris et al., 1996
). The present

study used functional magnetic
Top


Abstract


Introduction


Materials & Methods


Results


Discussion


References


Top


Abstract


Int
roduction


Materi
als & Methods


Results


Discussion


References


resonance imaging (fMRI) during

the

presentation of backwardly masked facial expressions to determine

whether
amygdala activation might be demonstrated in humans in

the absence of explicit knowledge.


A backward masking procedure previously demonstrated to interrupt processing of emotionall
y expressive faces
(Esteves and

Öhman, 1993
; Rolls and Tovee, 1994
) was used. Each mas
ked stimulus

consisted of a 33

msec
fearful or happy expression face (target),

its offset coincident with the onset of a 167

msec neutral expression

face
(mask). Esteves and Öhman (1993)

demonstrated that if the

stimulus onset asynchrony (SOA; i.e., the interval
between the

onset of the target and
the mask) was sufficiently brief (<40

msec), human subjects were not aware of the
emotionally expressive

target face, as defined by objective forced choice tasks and subjective

report. In the present
study 10

human subjects viewed repeating

28

sec epochs t
hat consisted of either fearful faces masked by

neutral
faces, happy faces masked by neutral faces, or a single

cross (+) that served as a fixation point baseline. We predicted

that, although subjects would report seeing only the neutral masks,

blood oxyge
n level
-
dependent (BOLD) fMRI
signal intensity (Kwong

et al., 1992
; Ogawa et al., 1992
) would increase in the amygdala

in response to masked
fearful targets when compared with masked

happy targets. In addition, we predicted that presentation of

masked
emotional facial expressions would serve to isolate amygdala

activation in contrast to pre
vious neuroimaging studies
of nonmasked

facial expressions, which have demonstrated activation of the

amygdala along with numerous
additional brain regions (Breiter

et al., 1996
; Morris et al., 1996
).





MATERIALS AND METHODS

Subjects.
Ten right
-
handed males aged 19
-
32 (mea
n, 23.8

years) provided informed consent before participation in
this study,

according to guidelines established by the Subcommittee on Human

Studies at the Massachusetts General
Hospital. Handedness was

defined by the Edinburgh Inventory (Oldfield, 1971
). Subjects

were told that they would
be pres
ented with pictures of faces.

All subjects were naive to the face stimuli used and to our hypotheses

pertaining
to the emotional expressions of faces. For this initial

experiment a single gender cohort was studied to minimize
heterogeneity,

thereby improvi
ng statistical power. Future studies of female

subjects will be necessary to determine
the generalizability of

the current results.

Selection of fear faces as threat
-
related stimuli.
Face stimuli consisted of fearful, happy, and neutral expressions of
eig
ht

individuals (numbers 021,

030,

040,

081,

101,

121,

131,

140; Ekman

and Friesen, 1976
). We selected fearful
faces as our negatively

valenced stimuli because human lesion studies document a deficit

in the processing of fearful
faces after amygdala lesions (Adolphs

et al., 1995
; Calder et al., 1996
), and previous neuroimaging

studies
demonstrate amygdala activation to these stimuli (Bre
iter

et al., 1996
; Morris et al., 1996
). We offer the concept
that,

unlike an angry face

that represents a direct threat, the relationship

of a fearful face to threat is ambiguous in that
a fearful face

signals the presence of danger, but not its source. In this sense,

a fearful face can be conceptualized as a
contextual stimulus,

whereas an
angry face can be conceptualized as a specific cue.


Paradigm.
Subjects were presented with alternating 28

sec epochs of masked fearful face targets (F), masked happy
face targets

(H), or a single cross that served as a low
-
level fixation condition

(+). Du
ring each epoch subjects viewed
either 56

masked fearful

stimuli or 56

masked happy stimuli (each of eight fearful or happy

faces was masked by the
neutral expression for each of the other

seven individuals).

Masked stimuli were presented twice per second

in a random order. Each 200

msec masked stimulus consisted of a
33

msec fearful

or happy expression (target) immediately followed by a 167

msec

neutral expression (mask).

The order of 28

sec epochs containing 56

fearful or happy masked stimuli was counte
rbalanced within and across
subjects; one
-
half

of the subjects viewed masked fearful, followed by masked happy,

targets during their first run
(+,F,H,+,F,H,+,F,H,+); the other

half viewed masked happy, followed by masked fearful, targets

during their first

run
(+,H,F,+,H,F,+,H,F,+). Then the order of

fearful and happy target epochs was reversed for the second run

for all
subjects. These 10

epochs comprised a 4

min and 40

sec

run. Each subject viewed two runs.


Subject debriefing.
Subjective report measures
were used to assess the subjects' explicit knowledge of presented
masked facial

expressions of emotion after the completion of all stimulus presentations.

Immediately after the
experiment the subjects were asked to describe

any aspect of the presented face
s. Next, the subjects were asked

to
Top


Abstract


Introduction


Materials & M
ethods


Results


Discussion


References


comment on the emotional expressions of the faces. Then the

subjects were asked if they had seen any happy or
smiling faces

and asked if they had seen any fearful or afraid faces. Finally,

the subjects were shown all fac
e stimuli
(fearful, happy, and

neutral) and asked to point out the specific faces they had referred

to in response to earlier
questions.


Stimuli and apparatus.
Face stimuli consisted of PICT files that were assembled frame by frame into a film, using
Adob
e Premiere

software. Specialized hardware (Media 100,

Marlboro, MA) was used

to transfer the digital PICT
information to videotape synchronized

with the headsweeps of the VCR so as not to distort the stimuli.

A VCR was
used to play the tape, and the output

was projected

(Sharp XG
-
2000U LCD) onto a screen within the imaging
chamber,

viewable by a mirror (1.5

×

3.5

inches) ~6.5 inches from the subject's

face. The play speed of the VCR was
30

frames/sec, creating a

33

msec/frame presentation rate.


Pulse rate
was measured from the right index finger of all subjects during stimulus presentations via pulse oximetry
(In Vivo

Systems, Orlando, FL).

Functional magnetic resonance images were collected in a General Electric Signa 1.5

Tesla high
-
speed imaging
device (
modified

by Advanced NMR Systems, Wilmington, MA), using a quadrature head

coil. Our Instascan
software is a variant of the echo planar technique

first described by Mansfield (1977)
. Head stabilization was
achieved

with a plastic bite bar molded to each subject's dentition.


Image acquisition and d
ata analysis.
Our standard image acquisition protocol was used and previously has been
detailed elsewhere

(Cohen and Weisskoff, 1991
; Kwong, 1995
). An initial sagittal

localizer [spoiled gradient recall
acquisition in a steady state

(SPGR), 60

slices, resolution 0.898

×

0.898

×

2.8

mm] was performed

to provide a
reference for future slice s
election and for eventual

localization within Talairach space (Talairach and Tournoux,
1988
).

After automated shimming (Reese et al., 1995
) to maximize field

homogeneity, a magnetic resonance (MR)
angiogram (SPGR, resolution

0.78125

×

0.78125

×

2.8

mm) was acquired to identify large
-

and

medium
-
diameter
vessels. Then a set of T1
-
weighted hi
gh
-
resolution

transaxial anatomic scans (resolution 3.125

×

3.125

×

8

mm) was

acquired. For the functional series, asymmetric spin echo (ASE)

sequences were used to minimize macrovascular
signal contributions.

Functional ASE data were acquired as 15

contig
uous, interleaved,

horizontal 8

mm slices that
paralleled the intercommissural plane

(voxel size 3.125

×

3.125

×

8

mm; 100

images per slice, TR/TE/Flip

=

2800

msec/70 msec/90°).

Automated data analytic techniques began with a quantification of subject mot
ion and then correction, using an
algorithm developed

by Jiang et al. (1995)
, based on Woods et al. (1992)
. Both functional

and high
-
resolution
structural data were placed into normalized

Talairach space and resliced into 3.125

×

3.125

×

3

mm voxels

in the
coronal plane. Then data from individuals were baseline
-
normalized

and concatenated (
averaged). Nonparametric
statistical maps were

calculated with the Kolmogorov
-
Smirnov (KS) statistic, displayed

in pseudocolor, scaled
according to significance, and superimposed

on T1
-
weighted high
-
resolution images also placed into Talairach

space
and re
sliced in the coronal plane. Because we predicted

only amygdala activation to the present experimental
manipulation,

our a priori significance threshold (
p

<

6.6

×

10
4
) represents a Bonferroni
-
corrected 0.05

probability
level based

on the ~76 voxels that make up the amygdaloid region (Filipek

et al., 1994
).




RESULTS

Subject

debriefing


Immediately after the experime
nt, the subjects were asked to describe any aspect of the presented faces. Two of the
10

subjects

offered descriptions indicating that they had seen features of

the emotional target stimuli. The remaining
eight subjects were

asked next to comment on the em
otional expressions of the faces,

and all responded with
reference to the neutral mask stimuli alone.

Then the subjects were asked if they had seen any happy or fearful

faces.
All eight subjects reported that they had not seen these

expressions. Finally, t
hese eight subjects were shown all face

stimuli (fearful, happy, and neutral) and asked to point out the

specific faces they had seen. Subjects selected only
neutral faces.

Therefore, we present here brain activation data for the eight

subjects who reporte
d having seen only the
neutral faces.


Top


Abstract


Introduction


Materials & Methods


Results


Discussion


References


Pulse rate

data


Pulse rate was measured in the eight subjects who reported not having seen the masked fearful and happy faces
(sampled approximately

every 5

sec). Technical problems prevented measurement within

the m
agnet for two of these
subjects. Results revealed no significant

pulse rate changes to the presentation of fearful or happy faces

when
compared with one another or the fixation baseline condition

(
p

>

0.05).

fMRI

data


Figure
1

presents BOLD signal changes across whole brain in response to masked fearful faces versus masked happy
faces for

the eight subjects who demonstrated no expli
cit knowledge of the

presence of these stimuli. Note the relative
absence of activation

outside the amygdaloid region.


View larger version

(96K):

[in this window]


[in a ne
w window]




Figure 1.


Masked fearful faces versus masked
happy faces. Areas of significant activation
(
p

<

6.6

×

10
4
) across whole brain, presented
here as

57,

3

mm coronal slices

for the masked
fear versus masked happy contrast, for the eight

subjects who reported not having seen the fearful
or happy target

faces. All figures are displayed
according to radiological convention

(i.e.,
left

=

right; right

=

le
ft; top

=

superior;
bottom

=

inferior).

The most anterior slice is in the
top left corner
, and slices

proceed in a posterior
direction from
left

to
right

and then
down
.

The
colorized statistical map is superimposed over the
averaged

high
-
resolution structu
ral data for these
eight subjects. Both

functional and structural data
have been placed in a normalized

space according
to the coordinate system of Talairach and
Tournoux

(1988)
. All figures were smoothed by
using a Hamming nine voxel

1:2:1 kernel filter,
although activations were significant on

un
smoothed maps. Significant activation within
the amygdaloid

region is evident within two slices
in the third row (
yellow brackets
).

These two
slices represent Talairach coordinates in the
y
-
plane

of 0

(see Fig.
3
) and
6 (see Fig.
2
),
respectively. Note also

the relative lack of
activation across all other brain regions.

There is
an activation of the inferior prefrontal cortex (first

row, slice nine) that met the significa
nce level set
a priori

for the amygdala. Note that, although our
15

original horizontal

slice acquisitions covered
"whole brain," susceptibility from

the sinus space
causes signal dropout in portions of some brain

regions (see Results).



Figure
2
A

presents the most posterior coronal slice from the amygdaloid region of activation depicted in Figure
1
.
Significantly

higher BOLD signal is observed in the amygdala in response to

masked fearful faces
(467.56

±

0.41,

mean

±

SEM) when compared

with masked happy face
s (464.85

±

0.43,

mean

±

SEM). Four
contiguous

voxels within the right amygdala met the threshold for statistical

significance (
p

<

6.6

×

10

4
; see
Materials a
nd Methods). We then assessed the direction of

signal change to fearful or happy faces in comparison to
the fixation

baseline epochs. We considered only the four significantly activated

voxels from the fear versus happy
contrast depicted in Figure

2
A
; the masked fear versus fixation contrast revealed a significant

increase in signal
intensity, whereas the masked happy versus

fixation
contrast revealed a significant decrease in signal intensity.

For
this comparison we treated the four voxels in the amygdala

(defined by the overall fear vs happy contrast) as one
region

of interest (ROI). Mean signal intensity within this ROI demonstrated

a significant increase to masked fearful
faces and a significant

decrease to masked happy faces when compared with fixation (
p

<

0.05). Thus, the larger
overall fear versus happy statistical

effect (
p

<

6.6

×

10
4
) demonstrated across these four voxels depends on both a
response

to the fearful faces (increase) and the happy faces (decrease).

By considering only voxels activated in the
fear versus happy

contrast,

we are assured of describing only the nature of signal

changes specifically attributable to
the emotional expressions.



View larger version

(67K):

[in this window]


[in a n
ew window]




Figure 2.


Top.

Amygdala activation to masked
fearful versus masked happy faces.
A
, Coronal
display of the most posterior slice

depicting
activation within the region of the amygdala from
Figure

1
. Image parameters are as in Figure
1
.
Activation

depicted here

in the right amygdala
includes four contiguous voxels that significantly

increased in response to masked fearful faces
when compared with

masked happy faces
(
p

<

6.6

×

10
4
).
B
, Bar graph depicting changes
in BOLD signal intensity as

a function of repeated
stimulus presentations.
Bars

represent

the mean
percentage change of signal intensity per epoch in
response

to masked fearful and masked happy
f
aces (counterbalanced), as

compared with the
preceding and following low
-
level fixation
conditions.

Values reflect only the four voxels that
exceeded the Bonferroni
-
corrected

significance
threshold (depicted within
A
) for the masked
fearful

versus masked h
appy contrast.


Figure 3.


Bottom.

Amygdala/SI activation to
masked fearful versus masked happy faces.
A
,
Coronal display of the most anterior

slice
depicting activation within the region of the
amygdala from

Figure
1
. Image parameters are as
in Figure
1
. Not
e that the most

ventral portion of
this activation is within the temporal lobe

(where
the most anterior extent of the amygdala is
located). This

activation then extends dorsally into
the basal forebrain where

the sublenticular
substantia innominata (
SI
) is

located. Six voxels

met the Bonferroni
-
corrected significance
threshold (
p

<

6.6

×

10
4
).
B
, Enlargement of the
activation presented in
A

is presented

twice: o
nce
for masked fear versus fixation and again for
masked

happy versus fixation. Colors of enlarged
voxels represent significance

levels for the
original masked fear versus masked happy
contrast

as follows:
orange
,
p

<

6.6

×

10
4
;
red
,
p

<

0.005;
blue
,
p

<

0.05.

Although the significant
statistical

effect for the masked fear versus
masked happy contrast in the

ventral portion of
this activation (
amyg
) is attributa
ble to signal

increases to fearful faces and signal decreases to
happy faces

(similar to the amygdala activation in
Fig.
2
), the st
atistical

effect in the dorsal portion of
this activation (
SI
) is a result

of signal increases to
both fearful and happy faces in which increases

to
fearful faces are significantly larger
(
p

<

6.6

×

10
4
).



To delineate the effect of repeated presentations of these stimuli, Figure
2
B

pr
esents BOLD signal changes in the
amygdala

for the significant ROI depicted in Figure
2
A

across all epochs

of presentation. First,
notice that BOLD
signal in the amygdala

is always higher during presentation of masked fear faces when

compared with the contiguous
(counterbalanced) epoch of masked

happy faces. For this group of eight subjects the average percentage

of change in
signal i
ntensity between conditions (masked fear

vs masked happy) ranged from 0.77

to 0.35% across epochs. When

compared with the fixation baseline condition, signal intensity

increases in response to fearful faces occurred during
the first

two fear presentation e
pochs but were attenuated to baseline with

subsequent stimulus presentations. In
contrast, however, note

that signal intensity decreases in response to happy faces persisted

through all presentation
epochs.


Figure
3
A

depicts BOLD fMRI signal changes for the masked fear versus happy contrast in the most anterior coronal
slice from

the amygdaloid region of activation depicted in Figure

1
. The

ventral portion of this activation is within the
temporal lobe,

where the most anterior extent of the amygdala is located;
however,

this activation extends
immediately rostral and dorsal to the

traditionally defined amygdala within the region of the sublenticular

substantia
innominata (SI) of the basal forebrain (see Heimer

et al., 1997
). Within the SI this activation extends in a
dorsomedial

direction to the base of t
he anterior commissure.


Although BOLD signal changes in the ventral portion of this activation increased to fearful faces and decreased to
happy faces

(similar to the activation in Fig.
2
), significant BOLD signal

changes in the dorsal portion of this
activation for the masked

fear versus masked happy contrast (
p

<

6.6

×

10
4
) were created by signal increases to
both

fearful and happy faces,

in which increases to fearful faces were significantly larger.

Figure
3
B

presents an
enlargement of the significant voxels of

activation from the masked fear versus masked happy contrast pictured

in
Figure
3
A
. The activation is presented twice: once for the

fear versus fixation contrast and again for the happy versus
fixation

contrast. Numbers overlying the voxels present the average percentage

of BOLD signal
change from the
fixation baseline across all stimulus

presentations. Note that, in response to masked fear faces, all

voxels of
activation
the most ventral voxels l
ocated in the amygdala

and the most dorsal voxels located in the SI
demonstrate signal

increases. In contrast, in response to masked happy faces, ventrally

located
voxels demonstrate
signal decreases (similar to the amygdala

response depicted in Fig.
2
), whereas dorsal voxels located in

the SI
demonstrate signal increases.


Table
1

presents Talairach coordinates (Talairach and Tournoux, 1988
) and probability values of activated brain
regions for

the masked fear ver
sus happy contrast for the eight subjects that

reported not having seen the masked
fearful and happy faces. Activation

within the left and right amygdala exceeded the a priori threshold

for significant
activation (
p

<

6.6

×

10
4
). To obviate bias, we report here all areas of activation across

whole brain that met this
threshold. One other brain area, left

inferior prefrontal cortex, also met this criterion (see F
ig.

1
, row one, slice nine).
Because it was not predicted, we note

then that activation in this region did not achieve the appropri
ate

Bonferroni
-
corrected threshold for whole brain (
p

<

1.0

×

10
7
).



View this table:


[in this window]

[in a new
window]




Table 1.



Talairach coordinates for masked fearful vs
masked happy faces


Technical

considerations


Quan
tification of motion
Corrected motion during functional image acquisition was <1.5 mm for all subjects.
Missing data
A

computer failure during image acquisition of subject number 7

caused his first run to be lost. This
did not affect the results,

because statistical effects were similar whether six, seven, or

eight subjects we
re considered.
The fact that the results were

similar to those of six subjects is important, because loss of

these data did not
compromise the protection afforded by counterbalancing.

Vessel effects
To rule out the possibility that the
observed activations

were attributable to flow through large vessels located medial

to the temporal lobe (e.g., inferior
carotid, middle cerebral

artery), we acquired MR angiograms for

these eight subjects, placed

them into normalized
Talairach space, and then averaged them across

the subjects. Thus, the composite activations for eight subjects

did not
overlie the location of large vessels on averaged MR angiograms.

Susceptibility artif
act
It is unlikely that the
observed activation

is an artifact of changes in the nearby field of susceptibility

because (1) inspection of animated
raw signal intens
ity changes

over time revealed no obvious systematic changes in susceptibility

that mirrored
counterbalanced conditions, and (2) these results

(i.e., increased signal to fear, decreased signal to happy) are

consistent with a previous positron emission tomo
graphy (PET)

study using nonmasked stimuli, where susceptibility
is not a concern.





DISCUSSION

Significance of amygdala activation to masked

stimuli


Amygdala activation wa
s observed in response to masked fearful faces versus masked happy target faces that subjects
reported

not having seen. As predicted, the backward masking of emotional

facial expressions resulted in impressive
isolation of the amygdala.

This finding is par
ticularly striking when considered in light

of an earlier neuroimaging
study demonstrating activation of the

amygdala and four additional brain regions to presentation of

nonmasked fearful
faces versus happy faces (Morris et al., 1996
).


These data highlight the automaticity of the amygdala respons
e and are consistent with the assertion of LeDoux
(1996)

that

the amygdala responds to early, crude representations of external

stimuli. Although consistent with the
notion that the amygdala

might receive stimulus information directly from the thalamus

(LeDoux et al., 1985
), prior
or parallel to elaborate cortical

processing, the temporal r
esolution of the present design (based

on 28

sec epoch
lengths) does not address this issue directly.

In addition, portions of candidate cortical areas that also might

survey
masked facial stimuli [e.g., temporal visual cortex (Hasselmo

et al., 1989
) and ventral prefrontal cortex (Tranel et
al., 19
95
;

Hornak et al., 1996
)] may not have been visualized in the present

study because of

characteristic signal
drop
-
out associated with

fMRI caused by the nearby sinus space. Replication of the present

effect using PET (where
susceptibility drop
-
out is not an issue)

would address this concern.

Direction of signal changes in the

amygdala


Wit
hin the amygdala, signal intensity increased to masked fear faces and decreased to masked happy faces, consistent
with

a previous imaging study (Morris et al., 1996
). In addition, signal

increases to masked fearful faces habituated.
Habituation of response

within the amygdala to emotionally valence
d stimuli that have

proven inconsequential is
consistent with previous reports in

both animals (Bordi et al., 1993
) and humans (Breiter et al.,

1996
; Irwin et al.,
1996
). In contrast, however, signal intensity

decreases in response to happy faces persisted through all presentation

epochs. Happy faces appear to provide information of enduring

importance and, in this sense, might be
conce
ptualized as safety

signals. One interpretation of these data is that both fearful

and happy faces provide
information about the potential for threat

in a given environment, differentially affecting the level of

activity in the
amygdala.

This differential

amygdala response, based on the valence of facial expressions, is consistent with a recent study of
human

infants in which presentation of negatively valenced (angry) faces

produced increased eyeblink magnitudes
and positively valenced

(happy) faces produ
ced decreased eyeblink magnitudes [Balaban

(1995)
; see also Lang
(1995)
]. Activation of
the amygdala is known

to modulate eyeblink reflex sensitivity (Davis, 1992
). To elaborate,

although direct electrical stimulation of the amygdala in animals

does not produce an eyeblink, the magnitude of the
next eyeblink

that is elicited after amygdala stimulation is modified (Whalen

and Kapp, 199
1
). These converging
results imply that, al
though

amygdala activation to experimental presentation of emotionally

valenced facial
expressions may not produce obvious overt responses,

it modifies overt responses to
subsequent

sensory information