Emotion
Emotional Appraisal Is Influenced by Cardiac Afferent
Information
Marcus A. Gray, Felix D. Beacher, Ludovico Minati, Yoko Nagai, Andrew H. Kemp, Neil A.
Harrison, and Hugo D. Critchley
Online First Publication, October 10, 2011. doi: 10.1037/a0025083
CITATION
Gray, M. A., Beacher, F. D., Minati, L., Nagai, Y., Kemp, A. H., Harrison, N. A., & Critchley, H.
D. (2011, October 10). Emotional Appraisal Is Influenced by Cardiac Afferent Information.
Emotion. Advance online publication. doi: 10.1037/a0025083
Emotion
2011, Vol. ●●, No. ●, 000 – 000
© 2011 American Psychological Association
1528-3542/11/$12.00 DOI: 10.1037/a0025083
Emotional Appraisal Is Influenced by Cardiac Afferent Information
Marcus A. Gray
Felix D. Beacher
Monash University and University of Sussex
Stony Brook University and University of Sussex
Ludovico Minati
Yoko Nagai
Fondazione IRCCS Instituto Neurologico “Carlo Besta,” Milano,
Italy, and University of Sussex
University of Essex and University of Sussex
Andrew H. Kemp
Neil A. Harrison
University of Sydney
Millview Hospital, Hove, UK, and University of Sussex
Hugo D. Critchley
Millview Hospital, Hove, UK, and University of Sussex
Influential models highlight the central integration of bodily arousal with emotion. Some emotions, notably
disgust, are more closely coupled to visceral state than others. Cardiac baroreceptors, activated at systole
within each cardiac cycle, provide short-term visceral feedback. Here we explored how phasic baroreceptor
activation may alter the appraisal of brief emotional stimuli and consequent cardiovascular reactions. We used
functional MRI (fMRI) to measure brain responses to emotional face stimuli presented before and during
cardiac systole. We observed that the processing of emotional stimuli was altered by concurrent natural
baroreceptor activation. Specifically, facial expressions of disgust were judged as more intense when presented
at systole, and rebound heart rate increases were attenuated after expressions of disgust and happiness. Neural
activity within prefrontal cortex correlated with emotionality ratings. Activity within periaqueductal gray
matter reflected both emotional ratings and their interaction with cardiac timing. Activity within regions
including prefrontal and visual cortices correlated with increases in heart rate evoked by the face stimuli, while
orbitofrontal activity reflected both evoked heart rate change and its interaction with cardiac timing. Our
findings demonstrate that momentary physiological fluctuations in cardiovascular afferent information (1)
influence specific emotional judgments, mediated through regions including the periaqueductal gray matter,
and (2) shape evoked autonomic responses through engagement of orbitofrontal cortex. Together these
findings highlight the close coupling of visceral and emotional processes and identify neural regions mediating
bodily state influences on affective judgment.
Keywords: baroreceptor, emotion, homeostasis, fMRI, disgust expressions
Supplemental materials: http://dx.doi.org/10.1037/a0025083.supp
Emotions encompass subjective experiences (feelings and perceptions) supported by physiological states. Influential theories
emphasize the coupling of emotional feelings to the experience of
changes in internal physiology (James 1894; Lange 1885). This
relationship has gained renewed appreciation through experimental observation (Craig, 2002, 2003; Critchley et al., 2002, 2004;
Marcus A. Gray, Psychiatry, Brighton and Sussex Medical School
(BSMS), and Centre for Consciousness Science, University of Sussex,
Brighton, UK, and Experimental Neuropsychology Research Unit,
School of Psychology and Psychiatry, Faculty of Medicine Nursing &
Health Sciences, Monash University, Melboure, Australia; Felix D.
Beacher, Psychiatry, Brighton and Sussex Medical School (BSMS),
University of Sussex, and Department of Biomedical Engineering,
Stony Brook University School of Medicine, Stony Brook University;
Ludovico Minati, Psychiatry, Brighton and Sussex Medical School
(BSMS), University of Sussex, and Scientific Directorate, Fondazione
IRCCS Istituto Neurologico “Carlo Besta,” Milano, Italy; Yoko Nagai,
Psychiatry, Brighton and Sussex Medical School (BSMS), University of
Sussex, and Department of Psychology, University of Essex, Essex,
UK; Andrew H. Kemp, School of Psychology, University of Sydney;
Neil A. Harrison, Psychiatry, Brighton and Sussex Medical School
(BSMS), University of Sussex, and Sussex Partnership NHS Foundation Trust, Sussex Education Centre, Millview Hospital, Hove, UK;
Hugo D. Critchley, Psychiatry, Brighton and Sussex Medical School
(BSMS), and Sackler Centre for Consciousness Science, University of
Sussex, and Sussex Partnership NHS Foundation Trust, Sussex Education Centre, Millview Hospital.
This study was supported by a Wellcome Trust Programme Grant to
H. D. Critchley. Neuroimaging was undertaken at the Clinical Imaging
Sciences Centre, Brighton and Sussex Medical School.
Correspondence concerning this article should be addressed to Marcus
A. Gray, Experimental Neuropsychology Research Unit, School of Psychology and Psychiatry, Faculty of Medicine Nursing & Health Sciences,
Monash University, Clayton, VIC, Australia 3800. E-mail: Marcus.Gray@
Monash.edu
1
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GRAY ET AL.
Damasio, 1994, 1999; Damasio, Tranel, & Damasio, 1991). There
is consequently increasing understanding of how feedback from
the body shapes emotions (Craig, 2002, 2003; Critchley et al.,
2004; Hobday et al., 2001; Harrison et al., 2009a, 2009b) and how
different emotions are supported by patterned changes in peripheral physiology (Ekman et al., 1983; Harrison et al., 2006).
The phasic discharge of arterial baroreceptors represents an
important source of visceral feedback. Baroreceptors are pressure
and stretch-sensitive receptors within the heart and surrounding
arteries, which are activated by ejected blood during each cardiac
cycle (at systole). Baroreceptor discharge primarily regulates
blood pressure (Katona et al., 1970), yet has broader influences.
Baroreceptor firing inhibits the activity of sympathetic nerves
supplying muscle, an effect that gates reactions to brief and surprising sensory stimuli (Kezdi & Geller, 1968; Koizumi et al.,
1971; Wallin et al., 2007). Baroreceptor activation also inhibits
pain processing, attenuating limb withdrawal (Edwards et al.,
2002, 2003; McIntyre et al., 2006; Rau et al., 1993), cardiovascular
reactions (Gray et al., 2009a), pain-evoked potentials and subjective pain ratings (Angrilli et al., 1997; Brody et al., 1997; Brody &
Rau, 1994; Droste et al., 1994; Dworkin et al., 1994; Gray et al.,
2010; Kardos et al., 1994; Mini et al., 1995; Rau et al., 1993).
While baroreflex regulation of blood pressure is effected by feedback through brainstem nuclei, baroreceptor afferents also project
further up the neuroaxis to thalamus (Oppenheimer et al., 1998;
Zhang & Oppenheimer, 2000) and insular cortex (Zhang et al.,
1998, 1999). Recently, we identified influences on processing
shocks at the level of amygdala, insula, and periaqueductal gray
(PAG) where baroreceptor activation attenuates blood pressure
reactions (reflected in amygdala and insula function) and alters
sympathovagal balance (reflected in amygdala and PAG function
[Gray et al., 2009a]). Given the close coupling of peripheral
physiological and emotional states, we predicted that baroreceptor
activation directly influences the processing of emotional information. Previously, Critchley et al. (2005) reported differential influences of emotional expressions on heart rate changes during a
speeded-response emotion identification task, suggesting emotive
stimuli may automatically elicit differential changes in bodily
arousal which impact upon the emotional interpretation of these
stimuli. The influence of baroreceptor afferent information on the
regulation of cardiovascular response during emotional processing
and preparation of speeded behavioral responses, however, has not
to date been examined.
Here we explored the neural mechanisms mediating phasic
baroreceptor influences on emotional processing. We presented
emotional stimuli (pictures of facial expressions) briefly at specific
phases of the cardiac cycle (cf. Gray et al., 2009a). We hypothesized that intensity ratings of facial emotions would differ as a
function of stimulus-timing relative to the cardiac cycle. Further,
we hypothesized that physiological (heart rate) response that occur
during the anticipation of a speeded behavioral response would
also be influenced both by the content of the emotional probe and
by its timing in relation to the cardiac cycle. Lastly, we hypothesized that these effects would be mediated through a hierarchy of
viscerosensory brain regions including PAG, amygdala, and insula. We used functional MRI (fMRI) to extend knowledge gained
from previous investigations regarding neural mechanisms associated with cardiovascular regulation, emotional appraisal, and the
influence of afferent cardiovascular feedback on affective processes.
Experimental Procedures
Participants
The study was approved by the Brighton and Sussex Medical
School (BSMS) Research Governance and Ethics Committee. Data
were acquired from 37 participants (9 male and 28 female; mean
age ⫽ 28.2 years, SD ⫽ 5.6 years), screened to exclude people
with past or current neurological, physical, or psychiatric disorder
affecting brain function. Because of hardware failure, behavioral
response data (rating of emotional stimuli) was lost for 13 participants, and for a further three participants there was no observed
variance in behavioral rating data. Thus, data from a subsample of
21 participants (3 males and 18 females, mean age 27.1 year, SD ⫽
5.7 years) were analyzed with respect to changes in declarative
ratings of the emotional stimuli.
Procedure
Immediately before scanning, electrocardiography (ECG) and
pulse oximetry were acquired while participants rested (reclined)
in our psychophysics laboratory, allowing assessment of mean
pulse transit time. Three lead ECG was acquired (Ag-AgCl electrodes, Einthoven’s triangle, standard lead I configuration) via an
isolated preamplifier (Model 1902, CED Ltd., Cambridge, U.K.).
Pulse oximetry was recorded (both initially and subsequently in
the MRI scanner) at the finger (Nonin 8600FO, Nonin Medical
Inc., Plymouth, MN). Physiological waveforms were digitized and
recorded on PC (power1401, Spike2 v7 software, CED Ltd.). As
with previous methods, mean pulse transit time calculated as time
from ECG-R wave to peak finger pulse oximetry allowed predictive cardiac timing of stimuli during fMRI scanning (Gray et al.,
2009a, 2009b, 2010).
Experimental Task and Design
The experimental design employed a forewarned reaction time
task, where stimulus cue is followed, after an intervening delay
period, by an imperative cue signaling a speeded, reaction timed
response. This task reliably induces heart rate slowing during
response preparation as the imperative cue is anticipated (Frith &
Allen, 1983; Jennings et al., 2002). Modifying this task by combining the stimulus cue with discrete emotional facial expressions
provides a context in which emotional processing may modify task
induced heart rate change (Critchley et al., 2005). Further ensuring
that emotional cues are brief (100 ms duration) and presented at
specific points in the cardiac cycle additionally allows for the
influence of baroreceptor function to be explored. Using methodologies established in previous cardiac-paced experiments, stimuli
were presented at the end of cardiac diastole (indexed by the ECG
R-wave) when baroreceptors are largely silent, and at the end of
cardiac systole (approximately at the ECG T-wave) as baroreceptor impulses are processed centrally (Edwards et al., 2007, 2009;
Gray et al., 2009a; McIntyre et al., 2006). Accordingly, we predicatively timed the onset of emotional expression stimuli to coin-
CARDIAC AFFERENTS INFLUENCES EXPRESSION APPRAISAL
cide with either the ECG R-wave (⫺200 to 50 ms after R-wave) or
with ECG T-wave (100 to 500 ms after R-wave).
During the forewarned reaction time task, participants were
required to make a cued judgment as rapidly as possible. Basal
heart rate was measured during the first 3 s of each trial (before cue
onset) while a central fixation cross was displayed. Next the
emotional stimulus was rapidly displayed, followed by the word
“ready.” Emotional images depicted neutral, happy, sad, or disgust
facial expressions (30 images from each category, 15 male and 15
female, Karolinska Directed Emotional Faces; Lundqvist et al.,
1998). Emotional stimuli were timed relative to the immediately
preceding heartbeat, and were presented pseudorandomly (i.e., in
an event related fashion) during either the ECG R wave or ECG T
wave periods of the cardiac cycle. Participants were cued to
prepare their response rating of the perceived emotional intensity
of facial stimuli on a 1– 4 scale from “low intensity” to “high
intensity.” After a variable delay (minimum 5.39 s, M ⫽ 5.80 s,
SD ⫽ 0.28 s), the imperative stimulus prompted speeded response
(see Figure 1A). Subsequent analysis revealed highly successful
predictive cardiac timing of facial stimuli (see Figure 1B). The
experimental task was completed in a single scanning session,
consisting of 120 trials with an average interstimulus interval of
10.4 s, SD ⫽ 0.4 s. The presentation of face stimuli during specific
periods of a participants’ cardiac cycle inevitably introduced some
variability in interstimulus intervals. Additional null event trials
were included to facilitate estimation of neural responses. Across
all participants the mean task length was 21 min and 47 s, SD ⫽
34.31 s.
Physiological Data Processing
Interbeat interval (IBI) during the experiment was calculated
from pulse oximetry data. To combine IBI data from participants
with differing heart rates, IBI after each emotional expression
stimulus was interpolated into 100 ms time bins (⫺4000 to 12,000
ms) separately, for each subject, and normalized by setting the
prestimulus IBI to 100% for each stimulus occurrence. IBI data
3
was then down-sampled into 0.5-s bins, facilitating group comparisons across time with inherently stochastic IBI data (see Figure
2A). To directly test task-induced heart rate change, and the
influences of expression type and cardiac-timing, average IBI
change during the response preparation period was calculated by
averaging interpolated normalized IBI (1,500 to 5,000 ms after
facial stimuli).
MRI Acquisition and Preprocessing
Participants underwent structural MRI imaging using a Siemens
Avanto 1.5 Tesla MRI scanner (Siemens, Erlangen, Germany)
with vacuum fixation to minimize head movement. Functional
echo-planar datasets sensitive to BOLD (Blood Oxygen Level
Dependent) contrast were acquired with axial slices (anteriorposterior phase encode direction) tilted 30 degrees from intercommissural plane to minimize T2* signal dropout from orbitofrontal
and anterior temporal regions. Thirty-six 3 mm slices with a 0.75
mm interslice gap were acquired providing full brain coverage
with an in-plane resolution of 3 ⫻ 3 mm (TE 50 ms, volume TR
3,800 ms). Following acquisition of the functional dataset, full
brain T1-weighted structural scans were acquired from each participant (MPRAGE, 0.9 mm3 voxels, 192 slices, 11.4/4.4 ms
TR/TE, 300 ms inversion time, 250 ⫻ 250 mm2 FOV).
Images were preprocessed using SPM5 (update 3381, http://
www.fil.ion.ucl.ac.uk/spm/). The initial four functional volumes
were discarded to allow for equilibration of net magnetization and
the image origin set at the anterior commissure. Images were then
spatially realigned and unwarped, and spatially normalized to
standard MNI space (Montreal Neurologic Institute) via parameters calculated during segmentation of the mean functional image;
Ashburner & Friston, 2005), a procedure that iteratively corrects
for nonuniform image intensity, spatially normalizes gray matter,
white matter, and cerebrospinal fluid tissue classes, and segments
into tissue classes via Bayesian estimation of tissue type. Normalized functional scans were subsequently smoothed with an 8 mm
Gaussian smoothing kernel (Friston et al., 2000).
Figure 1. Experimental task and stimuli timing. (A) Participants completed a forewarned reaction time task
where brief emotional expressions were presented to coincide with phases of their cardiac cycle. (B) Predictive
presentation of brief emotional stimuli resulted in the majority of stimuli occurring around the ECG R-wave or
the ECG-T wave.
4
GRAY ET AL.
Figure 2 (opposite).
CARDIAC AFFERENTS INFLUENCES EXPRESSION APPRAISAL
Statistical Modeling
Functional imaging data were analyzed via two separate models
to investigate the influence of emotion expression and cardiac
timing on (1) subjective emotionality judgments and (2) taskassociated heart rate change. Functional imaging data was analyzed with the standard hierarchal model approach typically used
in SPM (Penny & Friston, 2003) and modeled in a stochastic event
related manner. Individual first level models were constructed with
a full factorial design, including eight regressors for all levels of
emotion (⫻4) and cardiac timing (⫻2). To reduce variance attributed to the error term, conditions of no interest were also modeled;
button responses, and face stimuli that did not occur within our
cardiac periods of interest (see Figure 1B). Separate models exploring behavioral ratings and heart rate change were constructed
at the first level. Within each, the parametric modulation of experimental conditions were of primary interest; Model 1 examined
emotional appraisal of facial stimuli, and Model 2 examined heart
rate changes during anticipation of the speeded response. Model 1
was necessarily restricted to include only participants with usable
behavioral rating responses (n ⫽ 21), where the neural response to
each of the four facial expression types were predicted by a finite
impulse response at stimulus onset convolved with the canonical
HRF (duration 0 s). Neural correlates of behavioral ratings were
then explored via first order parametric modulations of these
regressors, such that the neural response to each expression was
modulated by the behavioral rating score of that specific facial
expression. Second level analyses of parametric modulation regressors allowed examination of emotional appraisal, with comparable analysis of emotional visual stimulus processing presented
in supplementary material (see Supplementary materials section
S1, Figure S1, and Table S1; available online only).
Model 2, exploring heart rate change, included all 37 participants. Brain imaging data was constructed to match measures of
mean IBI change by modeling the period between emotional cue
and imperative cue with a 5-s boxcar convolved with the canonical
HRF. Similar to Model 1, neural correlates of heart rate change
were explored via first order parametric modulations of delayperiod regressors by the corresponding mean heart rate change
after each stimulus presentation. Second-level analyses of parametric modulation regressors allowed examination of heart rate
regulation during response preparation, with comparable analysis
of response preparation presented in supplementary material (see
Supplementary material section S3, Table S3, and Figure S3;
available online only). It should be noted that only the brief
presentation of expression stimuli (and not fMRI acquisition) was
synchronized with cardiac activity, and as a result, we expect no
consistent cardiovascular effects on averaged fMRI measures.
Based on previously published findings we specifically explored
activity within bilateral amygdala, bilateral insula, and PAG, in
5
addition to activity elsewhere within brain, by manually tracing
these structures, on the standardized template brain in MNI space
(avg152T1) using MRIcron version 18 (mask volume; bilateral
amygdala 399 voxels, bilateral insula 3726 voxels, PAG 363
voxels; see Supplementary material section S4, Fig S4 for mask
illustration; available online only). We report activations in clusters larger than 10 contiguous voxels that survive random field
theory FWE correction for whole brain or for regions of interest at
p ⬍ .05. Additionally, to fully characterize our findings, greater
than 10 contiguous voxel activations where p ⬍ .0001 uncorrected
are also reported.
Results
Subjective Emotional Appraisal and Cardiac Timing
Repeated measures ANOVA exploring the influence of expression type and cardiac timing on average ratings of expression
intensity showed a significant main effect of emotion (F(3, 60) ⫽
36.3, p ⬍ .0001). Main effect of cardiac timing (p ⫽ 1) and
interaction between emotion and timing (p ⫽ .5) were nonsignificant. Planned contrasts examining cardiac timing effects within
each expression type revealed a significant effect only for disgust
expressions (t(1,20) ⫽ 2.3, p ⫽ .03), with stimuli presented on the
T-wave judged to have greater emotional intensity those presented
on the R wave (sad [p ⫽ .8], happy [p ⫽ .5], neutral [p ⫽ .6]; see
Figure 2C).
Average Heart Rate Change and Cardiac Timing
We then examined influence of expression type and cardiac
timing on average change in IBI during response preparation for
all participants (n ⫽ 37). While we did not observe a significant
main effect for expression type (p ⫽ .9), there was a trend toward
a main effect of cardiac timing (F(1, 36) ⫽ 3.7, p ⫽ .06) and a
significant emotion by timing interaction (F(3, 108) ⫽ 4.1, p ⫽
.008). Planned contrasts again revealed that cardiac timing influenced IBI changes following disgust (t(1,36) ⫽ 2.8, p ⫽ .009). IBI
changes after happy (t(1,36) ⫽ 2.4, p ⫽ .02), but not sad or neutral
expressions were significant (p ⫽ .2; see Figure 2A). Similar
effects were also seen when restricting analysis to the 21 participants with subjective rating data (see Supplementary Figure S2;
available online only).
Neural correlates of emotional stimulus processing and the
influence of cardiac timing. Emotional face stimuli, though
presented only briefly (100 ms), evoked strong activation of visual
cortical regions including calcarine sulcus and fusiform gyrus, and
within association cortices in parietal and frontal lobes and insula.
Reductions in activity were also observed within a matrix of brain
regions encompassing those referred to as the “default network”
Figure 2 (opposite). (A) Average interbeat interval data for a complete forewarned reaction time trial is displayed separately for the eight experimental
conditions (disgust, sad, happy, and neutral expressions ⫻ R-wave and T-wave presentation). IBI data is interpolated into 0.5 s bins, and displayed from
4 s before 12 s after brief emotional stimuli presentation (identified by light blue bars). Speeded behavioral ratings were initiated after an imperative cue
(identified by red bars). Data is the percent change in IBI for all 37 participants. (B) Average IBI change during response preparation after stimulus for
all 37 participants. (C) Behavioral ratings of the perceived emotional intensity of facial expression stimuli. Data is from all subjects with available
behavioral response data (n ⫽ 21). See Supplementary Figure 1 (available online only) for comparable figure with n ⫽ 21 for panels A and B.
GRAY ET AL.
6
including posterior and subgenual cingulate cortices (see Supplementary Figure S1 and Table S1; available online only). Neural
activity directly evoked by face stimuli was not modulated overall
by timing within the cardiac cycle.
Table 2
Influence of Cardiac Timing on Correlations Between BOLD
and Emotional Appraisals
Region
Neural Correlates of Subjective Appraisal and the
Influence of Cardiac Timing
Behavioral ratings were weakly predicted by neural activity at
the time of stimulus presentation. We observed a positive correlation within medial frontal gyrus and negative correlations also
primarily within prefrontal regions (see Table 1).
Importantly, we also observed that cardiac timing modulated the
neural activity related to subjective appraisal of emotional intensity (see Table 2) through further engagement of PAG (see Figure
3A), prefrontal and precentral regions. PAG was also significantly
negatively correlated overall with intensity ratings, The negative
association between PAG activity and rated intensity was significantly greater after R-wave synchronous expressions, relative to
T-synchronous expressions (as was also the case within inferior
frontal and precentral gyral cortices). The converse exploration,
investigating greater correlations following T-wave relative to
R-wave synchronized emotional expressions did not reveal any
significant neural correlates.
Neural Correlates of Heart Rate Change and the
Influence of Cardiac Timing
We next explored neural activity during the responsepreparation interval (see Supplemental Figure S3 and Table S3 for
simple main effects; available online only), and in particular, the
association between neural activity and evoked heart rate change
(i.e., the parametric modulation). When considering all conditions,
strong positive associations were observed across widespread regions of brain. Gray matter associations were observed within
primary and secondary visual areas, cerebellum and frontal re-
Side Cluster k
Greater correlations after R-wave
than T-wave synchronous
stimuli
Inferior frontal gyrus
Precentral gyrus
PAG
ⴱ
p ⬍ .0001 uncorrected.
ⴱⴱ
L
R
R
27
23
194
Positive correlations between BOLD
signal and subjective ratings
Middle frontal gyrus
Negative correlations between
BOLD and subjective ratings
Middle frontal gyrus
Inferior frontal gyrus
Middle frontal gyrus
Post central gyrus
Middle frontal gyrus
Cerebellum
Superior temporal gyrus
Caudate nucleus
Superior parietal lobule
Lateral sulcus
Insula (posterior)
Insula (anterior dorsal)
PAG
ⴱ
p ⬍ .0001 uncorrected.
ⴱⴱ
⫺58 20 10 4.37ⴱ
34–12 58
3.93ⴱ
6–34–12
3.99ⴱⴱ
gions, and with the amygdala and insula regions of interest (see
Table 3). We observed no negative correlation with BOLD signals,
even at uncorrected thresholds.
Again, we also tested whether the neural activity coupled to
stimulus-induced changes in heart rate was modulated by timing of
stimuli within the cardiac cycle, and we observed two complementary effects. Considering all emotions together, we observed no
significant influence of cardiac timing on gray matter activity.
When specifically considering the processing of disgust expressions, after which preparatory heart rate significantly differed
according to the cardiac timing of stimuli, left orbitofrontal cortex
activity showed significantly greater positive coupling to heart rate
following R-wave than T-wave synchronized stimuli. Importantly,
cardiac timing effects within the OFC colocalized with OFC
activity previously identified to reflect task associated changes in
heart rate (see Tables 3 and 4, and Figure 4). No significantly
different associations with heart rate were observed in either
direction when considering happy expressions alone.
Discussion
Cardiac baroreceptor responses are an important source of visceral afferent input to the brain and have previously been shown to
Side
Cluster k
L
87
L
L
R
R
R
R
R
L
R
R
L
L
R
379
263
330
50
131
37
145
36
139
97
24
16
34
p ⬍ .05 FWE ROI.
T
p ⬍ .05 (FWE ROI).
Table 1
Neural Activity Predicting Subjective Appraisal of Emotional Intensity
Region
MNI
MNI
T
⫺8 40 48
4.46ⴱ
⫺50–16 52
⫺56–34 16
20 2 62
52–20 26
36 30 36
26–40–50
56–32 8
⫺16–22 22
20–66 60
62 0 0
⫺56–32 18
⫺30 14 12
6–32–14
5.54ⴱ
4.76ⴱ
4.42ⴱ
4.36ⴱ
4.33ⴱ
4.09ⴱ
4.02ⴱ
3.90ⴱ
3.97ⴱ
3.90ⴱ
4.62ⴱⴱ
4.00ⴱⴱ
3.86ⴱⴱ
CARDIAC AFFERENTS INFLUENCES EXPRESSION APPRAISAL
7
Figure 3. Influence of cardiac timing on subjective appraisal. Above: Neural activity negatively correlated with
emotionality ratings within the PAG (displayed in red). Cardiac timing differentially modulated these associations within partially overlapping regions of the PAG (displayed in yellow). Below: Associations between
spatially averaged PAG activity and emotionality ratings of T-wave and R-wave stimuli are illustrated for each
participant; stronger negative correlations are observed following R-wave stimuli.
alter simple reflexes and perception of pain evoked by strong
somatosensory stimulation (Angrilli et al., 1997; Brody & Rau,
1994; Droste et al., 1994; Kardos et al., 1994; Mini et al., 1995).
The central aim of this study was to explore how emotional
appraisal and physiological responses to brief experimental stimuli
are similarly influenced by concurrent baroreceptor activation,
operationalized here by synchronizing brief visual stimuli with
different phases of the cardiac cycle. Here we provide primary
evidence that subjective appraisal of emotional facial expressions
is influenced by phasic visceral feedback, notably constrained to
the rating of disgust expressions. Autonomic (heart rate) responses
to brief emotional stimuli were similarly influenced by cardiac
timing. Again effects were restricted to specific emotional expressions; in this case both disgust and happiness. Furthermore using
functional neuroimaging, we were able to identify brain mechanisms likely mediating cardiac afferent influences on appraisal and
physiological responses at the level of the PAG, dorsolateral, and
orbitofrontal cortices.
In our study, face stimuli were presented only briefly and were
unlikely to induce the corresponding emotional feeling state within
participants. Nevertheless, our results suggest that emotionality
judgments of facial expression stimuli are influenced by subtle
alterations in physiological state occurring without consciousness
awareness. The now-classic finding that activation of facial muscles alone unwittingly influences the rating of affective stimuli
(participants held a pen in teeth or lips thereby covertly emulating
a smile or pout), is in keeping with a general integration of
information about one’s own body state when evaluating the
emotional content of stimuli (Strack et al., 1988). Micromimicry in
response to emotional face stimuli presented consciously (SonnbyBorgström, 2002) or unconsciously (i.e., as masked stimuli; Dimberg et al., 2000) can be demonstrated using measures of facial
GRAY ET AL.
8
Table 3
Neural Activity Predicting Heart Rate Change During Response
Preparation
Region
Side Cluster k
Significant correlations between
BOLD signal and heart
rate
Fusiform gyrus
Fusiform gyrus
Medial frontal gyrus
Superior frontal gyrus
Cerebellum
Orbito-frontal gyrus
Precentral gyrus
Lateral sulcus
Superior frontal gyrus
Medial frontal gyrus
Calcarine sulcus
Amygdala
Insula (anterior dorsal)
Insula (mid ventral)
ⴱ
p ⬍ .05 (FWE whole brain).
R
L
L
R
L
L
R
L
R
R
R
R
R
R
ⴱⴱ
11046
150
128
128
35
26
30
37
48
28
31
59
24
25
MNI
T
38–74–22
10.26ⴱ
⫺28–42–44 6.74ⴱ
⫺30 62 0
6.50ⴱ
6–2 72
6.19ⴱ
⫺6–52–26
6.13ⴱ
⫺14 14–16
5.96ⴱ
52–8 54
5.93ⴱ
⫺64–18 10
5.84ⴱ
28 62–4
5.74ⴱ
36 58 10
5.47ⴱ
2–82 6
5.33ⴱ
20 2–18
4.70ⴱⴱ
32 16 14
4.26ⴱⴱ
44–6 ⫺10
4.09ⴱⴱ
p ⬍ .05 (FWE ROI).
muscle activity, further indicating the integration of changes in
bodily state (independent of conscious awareness) with affective
processing including explicit judgments. In the present study, we
observed that inferior prefrontal, precentral, and PAG activity
differentially reflected emotionality judgments of facial expression
stimuli depending on cardiac timing. Activity within the inferior
frontal gyrus is frequently associated with evaluation of social
information including facial expression (Chakrabarti et al., 2006;
George et al., 1993; Li et al., 2009; Nakamua et al., 1999;
Sprengelmeyer et al., 1998). Lesions within ventrolateral and
orbitofrontal regions can impair the recognition of facial expressions (Hornak et al., 1996; Rolls et al., 1994). Our observation that
left dorsolateral prefrontal activity reflects emotional judgments,
which in turn are differentially influenced by cardiac timing,
suggests a point at which afferent baroreceptor information is
integrated in the appraisal of facial stimuli.
Our data specifically highlights the role of the PAG as a mediator of the effect of cardiac timing on emotional judgment. The
PAG contributes to the regulation of anxiety, defensive motor and
autonomic responses to surprising or threatening stimuli (Fields &
Basbaum, 1999; Mason, 2005; Mobbs et al., 2009). Anatomically,
PAG is connected reciprocally to insula, amygdale, and to medullary centers, including rostral ventrolateral medulla (RVLM),
where cardiovascular responses are heart rate regulated (Behbehani, 1995). Columns within PAG exert differential effects on
blood pressure (Lovick, 1992; van der Plas et al., 1995). Our
observation that cardiac timing influences on emotionality judgments are reflected in differences in functional activity within
PAG and prefrontal cortex highlights this integrative coupling of
cognition with autonomic control.
In addition to influences on affective judgment, cardiac afferents
also influenced heart rate changes observed while delaying a
speeded motor response. Again, cardio-visceral influences were
restricted to specific emotional content, namely processing of
disgust expressions. Critchley et al. (2005) observed differential
heart rate responses during forewarned reaction time task dependant on specific emotional expressions. Here also disgust and
happy heart rate responses were attenuated relative to other expression types (sad and angry expressions). Our results suggest
that heart rate increases during the preparation of speeded responses reflect the release of heart rate inhibition during anticipation of the imperative response stimulus. In this case, central
processing of brief visual stimuli simultaneously with baroreceptor
impulses reveal an attenuation of (rebound) increases in heart rate.
This attenuation, observed when disgust and happy expressions are
presented at diastole is reflected by functional activity within mid
orbitofrontal cortex.
The orbitofrontal cortex supports the integration of cognitive
and perceptual cross-modal representations with motivationally
salient physiological information (including hunger and satiety)
and is a cortical source of descending influences on internal bodily
state. Neuroanatomically (Barbas et al., 2003, 2000) orbitofrontal
regions are heavily and bidirectionally connected to midbrain and
pontine-medullary nuclei with direct regulatory control over a
number of distinct sympathetic efferent pathways, including importantly cardiovascular regulatory systems. Functionally, orbitofrontal activity is implicated both in the processing of facial
expressions and the regulation of experimentally induced physiological responses (Critchley, 2009; Ishai, 2007; Kranz & Ishai,
2006; O’Doherty et al., 2001; Mühlberger et al., 2010; Piché et al.,
2010). Given this integrative role of orbitofrontal cortex, our
identification of localized orbitofrontal activity predicting heart
rate response to emotional stimuli may not be particularly surprising; however, the additional observation that activity within this
circumscribed orbitofrontal region is sensitive in this role to short
term fluctuations in visceral state extends our understanding of
interaction between conscious emotional processing and afferent/
efferent regulation of ongoing cardiovascular state.
Importantly, our observations were largely confined to effects
on processing of disgusted facial expressions. The emotion of
disgust, in comparison to other negative emotions such as fear,
sadness and anger, is more closely coupled to parasympathetic
responses. Thus, heart rate slows in association with self-induced
feelings of disgust (as well as with induced feelings of happiness;
Table 4
Influence of Cardiac Timing on Correlations Between BOLD and Heart Rate Change
Greater correlations after R-wave than T-wave
synchronous stimuli
Disgust specific
ⴱ
p ⬍ .0001 uncorrected.
Region
Side
Cluster k
MNI
T
Orbito-frontalgyrus
L
24
⫺14 14–16
4.32ⴱ
CARDIAC AFFERENTS INFLUENCES EXPRESSION APPRAISAL
9
Figure 4. Intracranial correlates of mean heart rate change and the influence of cardiac timing. (A) Cardiac
timing influences on neural predictions of heart rate change following disgust expressions were observed within
left OFC. (B) Cardiac timing influences on heart rate change (in yellow) overlap with overall associations
between BOLD signal and heart rate in left OFC (in red; associations in other regions exclusively masked for
display).
Ekman et al., 1983). Increased baroreceptor firing ultimately slows
heart rate through a parasympathetic (vagus nerve-mediated) reflex that accompanies the vasodilatation cause by direct inhibition
of sympathetic activity to arterioles in the skeletomusculature
(Abboud, 1979; Kircheim, 1976). This specific relationship with
parasympathetic control may underlie the impact of cardiac timing
on disgust perception, and the cardiac responses to disgust and
happy faces. The augmentation of disgust-induced parasympathetic responses by timing within the cardiac cycle may thus
enhance the representation of disgust stimulus and corresponding
emotion perception. In this respect it would seem that the generation of the efferent reaction may be ultimately responsible for the
enhanced rating. Nevertheless, we did not identify a direct association between heart rate effects and emotionality judgments, and
we failed to identify overlap in neural activity reflecting baroreceptor influences on heart rate and on emotionality judgments.
Therefore, our findings suggest that cardiac timing influences on
the attenuation of heart rate recovery and on emotionality judgments may be mediated by partially independent neural systems.
These findings complement evidence from studies of other
interoceptive modalities which highlight a major role of insula
as viscerosensory cortex engaged alongside the cingulate gyrus,
orbitofrontal cortex, and amygdala (e.g., Craig, 2002, 2003,
2009; Critchley, 2009; Gray & Critchley, 2007b; Gray et al.,
2007a; Medford & Critchley, 2010). In the present study, both
insula and amygdala activity reflected task-associated changes
in heart rate. These regions also share a role in the evaluation
and processing of affectively salient stimuli including the emotional expressions of others, although they did not predict
emotionality judgments in the present study. Surprisingly, there
have been only a handful of neuroimaging studies that directly
address the neural mechanism through which bodily state might
influence the processing of emotional expressions in others.
Phillips and coworkers (2003) used negative emotional faces as
a modulatory context to examine responses to direct visceral
stimulation and demonstrated significant interaction between
face and visceral processing that was associated with enhanced
anterior cingulate and insula response. Visceral context has also
been shown to influence processing of valenced faces in patients with autonomic deficits (Critchley et al., 2002; Nicotra et
al., 2006) and in the context of peripheral inflammation (Harrison et al., 2009). There is however a paucity of data regarding
very short-term effects of natural fluctuations in visceral state.
Previously we suggested that higher order representation of
bodily arousal are perhaps more important in biasing affective
judgments of others emotions than representations more proximal to physiological state: False subjective beliefs of increased
heart rate enhance emotionality rating of neutral faces, an effect
reflected by functional changes within insula and amygdala
(Gray et al., 2007c). Conversely, in the present study, ‘lowerlevel’ baroreceptor influences on emotionality judgments (observed within PAG and prefrontal cortex) were closely coupled
to neural mechanisms supporting face perception and arousal
regulation. Our recent observations that attention interacts with
baroreceptor afferents in influences on cortical pain evoked
potential amplitude provides further support for the interrelatedness of autonomic afferents, ongoing autonomic regulation,
and cognition (Gray et al., 2010). Together, these findings
extend our knowledge over integration of physiological afferent
information with emotional processing by differentiating effects on disgust appraisal and accompanying heart rate responses. Our study highlights the contribution of afferent baroreceptor information conveyed from the heart and great vessels
to brainstem via vagus nerve afferents, and identifies separate
neural activity mediating baroreceptor influences on emotionality judgments and simultaneous regulation of heart rate responses. These behavioral effects have important implications,
characterizing the suspected influence of short term visceral
changes on affective processes and highlighting an important
channel through which this may operate.
GRAY ET AL.
10
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Received September 30, 2010
Revision received June 6, 2011
Accepted June 6, 2011 䡲