Heightened emotional contagion in mild cognitive
impairment and Alzheimer’s disease is associated
with temporal lobe degeneration
Virginia E. Sturm1, Jennifer S. Yokoyama, William W. Seeley, Joel H. Kramer, Bruce L. Miller, and Katherine P. Rankin
Memory and Aging Center, Department of Neurology, Sandler Neurosciences Center, University of California, San Francisco, CA 94158
Edited by Michela Gallagher, Johns Hopkins University, Baltimore, MD, and accepted by the Editorial Board April 22, 2013 (received for review
January 18, 2013)
Emotional changes are common in mild cognitive impairment
(MCI) and Alzheimer’s disease (AD). Intrinsic connectivity imaging
studies suggest that default mode network degradation in AD is
accompanied by the release of an emotion-relevant salience net-
work. We investigated whether emotional contagion, an evolu-
tionarily conserved affect-sharing mechanism, is higher in MCI
and AD secondary to biological alterations in neural networks that
support emotion. We measured emotional contagion in 237 par-
ticipants (111 healthy controls, 62 patients with MCI, and 64
patients with AD) with the Interpersonal Reactivity Index Personal
Distress subscale. Depressive symptoms were evaluated with the
Geriatric Depression Scale. Participants underwent structural MRI,
and voxel-based morphometry was used to relate whole-brain
maps to emotional contagion. Analyses of covariance found sig-
nificantly higher emotional contagion at each stage of disease
progression [controls < MCI (P < 0.01) and MCI < AD (P <
0.001)]. Depressive symptoms were also higher in patients com-
pared with controls [controls < MCI (P < 0.01) and controls < AD
(P < 0.0001)]. Higher emotional contagion (but not depressive
symptoms) was associated with smaller volume in right inferior,
middle, and superior temporal gyri (PFWE< 0.05); right temporal
pole, anterior hippocampus, parahippocampal gyrus; and left mid-
dle temporal gyrus (all P < 0.001, uncorrected). These findings sug-
gest that in MCI and AD, neurodegeneration of temporal lobe
structures important for affective signal detection and emotion in-
hibition are associated with up-regulation of emotion-generating
mechanisms. Emotional contagion, a quantifiable index of empathic
reactivity that is present in other species, may be a useful tool with
which to study emotional alterations in animal models of AD.
empathy|social behavior|simulation|affective resonance
prodromal stage, mild cognitive impairment (MCI) (2). De-
position of beta-amyloid plaques and neurofibrillary tangles, the
hallmark pathological changes in AD (3), is hypothesized to
begin decades before the emergence of cognitive symptoms and
subsequent functional decline (4). Emotional symptoms are also
common and have been found in 35–85% of patients with MCI
(5–7) and up to 75% of patients with AD (8), with depression
and anxiety the most frequent symptoms seen. Individuals with
MCI who have comorbid emotional complaints are more likely
to progress to dementia than those without such symptoms (9–
13). Taken together, these studies suggest that a clinical pre-
sentation that includes both cognitive decline and emotion dysre-
symptoms themselves may portend or even exacerbate disease
progression (9, 11, 14).
The medial temporal lobe is among the earliest sites of disease
in MCI and AD (2, 15), and hippocampal atrophy is associated
with worse episodic memory performance on standardized neu-
ropsychological testing (16) and predicts conversion from MCI
to AD (17). Similarly, functional imaging studies reveal di-
minished intrinsic connectivity, the degree to which distributed
rogressive deterioration of memory and other cognitive
functions characterizes Alzheimer’s disease (AD) (1) and its
brain structures fluctuate in synchrony in the absence of a struc-
tured task, in the default mode network in MCI and AD (18, 19).
The default mode network, which includes the medial temporal
lobe, posterior cingulate cortex, precuneus, medial prefrontal
cortex, and lateral temporoparietal cortex, supports various cog-
nitive processes including episodic memory (20, 21), a cognitive
function that is particularly vulnerable in AD. The hippocampus,
although most prominently known for its role in cognitive pro-
cesses such as episodic memory and spatial navigation (22, 23), is
also implicated in emotion. The anterior hippocampus, in par-
ticular, has rich connections with the hypothalamus and amygdala
(24, 25), which are structures important for emotion reactivity
(26), and plays an inhibitory role in affective behavior via its
projections to autonomic and endocrine emotion generation
systems (24, 27, 28). As default mode network integrity deterio-
rates in AD, there is a concomitant connectivity increase within
an emotion-relevant salience network (14). The salience network,
with hubs in pregenual anterior cingulate cortex and frontoinsula
and connections to emotion generators including the amygdala,
hypothalamus, and brainstem (26), is hypothesized to be essential
for survival-relevant affective stimuli detection and visceromotor
emotion generation (29). Heightened salience network connec-
tivity in healthy individuals has been associated with negative
emotional reactivity and glucocorticoid levels (e.g., cortisol), a
neuroendocrine index of the stress response (30). In AD, in-
creased salience network connectivity relates to neuropsychiatric
hyperactivity symptoms (e.g., agitation, irritability, aberrant motor
behavior, disinhibition, and euphoria) (31). Neurodegeneration of
medial temporal structures that support emotion inhibition (27, 28)
and lateral temporal structures that promote socioemotional pro-
cesses, including evaluation of faces (32), prosody (33), intention
(34), and trustworthiness (35), may alter affective physiology, be-
havior, and experience in MCI and AD.
Emotional contagion is a basic affective mechanism by which
an organism automatically synchronizes its physiological and
behavioral states with those of another to promote affective
simulation and altruistic behavior (e.g., helping) (36, 37). Via
salience network structures and emotion generators (26), emo-
tions can unfold without conscious awareness (36) and travel
rapidly from organism to organism through the activation of
visceromotor mirroring mechanisms (36–38). With deep onto-
genetic and phylogenetic roots, emotional contagion is present in
human infants, birds, rodents, and nonhuman primates, among
others (38, 39). Human neonates display this rudimentary form of
empathy and, from the first days of life, mimic facial expressions
(40) and share others’ distress, as demonstrated by studies in which
Author contributions: V.E.S., J.S.Y., W.W.S., B.L.M., and K.P.R. designed research; V.E.S.,
J.S.Y., and K.P.R. performed research; V.E.S., J.S.Y., J.H.K., and K.P.R. analyzed data; and
V.E.S. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission. M.G. is a guest editor invited by the Editorial
1To whom correspondence should be addressed. E-mail: email@example.com.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.
www.pnas.org/cgi/doi/10.1073/pnas.1301119110PNAS Early Edition
| 1 of 6
infants cry more after hearing the cries of other infants (but not
after hearing recordings of their own cries) (41). Rats are also
attuned to the affective cues of others and exhibit emotional
contagion via empathic distress vocalizations, physiological re-
activity, and activity in emotion-relevant brain structures (e.g.,
anterior cingulate cortex and amygdala) when in the presence
of another rat in distress. These reactions motivate prosocial
helping behavior (42, 43). Thus, emotional contagion is a simple
form of affect sharing that is at the core of more sophisticated
forms of empathy and is not dependent on higher-order cogni-
tive processing. An ecologically valid index of empathic reac-
tivity, emotional contagion can be examined across species and
in laboratory settings (39) and can be used to investigate the
integrity of neurobiological systems that support emotion.
In the present study, we used the Personal Distress subscale of
the Interpersonal Reactivity Index (IRI), a measure of emotional
empathy that indexes the degree to which an individual experi-
ences self-oriented feelings of anxiety and discomfort in negative
social situations (44), to investigate whether there are gains in
emotional contagion in individuals with MCI and AD (compared
with healthy controls) and whether emotional contagion en-
hancement is associated with brain atrophy in temporal lobe
structures with established roles in emotion. We conducted
whole-brain voxel-based morphometry analyses using structural
magnetic resonance images to relate emotional contagion to
regions of brain atrophy in a large sample that included indi-
viduals with MCI, those with AD, and healthy controls. Our
primary hypothesis was that neurodegeneration of the hippo-
campus in MCI and AD may lead to higher emotional contagion
secondary to less efficient emotion inhibition and salience net-
work release. Given that AD also affects lateral temporal lobe
structures with known roles in socioemotional stimulus detection
and comprehension (32, 34), we examined whether atrophy in
these structures may interfere with affective signal detection and
may also be associated with emotional contagion. We contrasted
our results with levels of self-reported depressive symptoms to
determine whether changes in emotional contagion reflected
broader mood dysregulation.
Emotional Measures. We found a main effect of diagnosis on
emotional contagion [F(2, 229) = 29.0, P < 0.001] (Fig. 1). There
was no main effect of sex [F(2, 229) = 3.0; P < 0.09], and the sex ×
diagnosis interaction was not significant [F(2, 229) = 0.9; P = 0.42].
Because there was no main effect or interaction with sex, we con-
ducted the post hoc analyses after removing sex from the model.
Tukey-Kramer pairwise comparisons revealed significantly higher
emotional contagion in MCI compared with healthy controls (P <
0.01), in AD compared with MCI (P < 0.001), and in AD compared
with healthy controls (P < 0.0001). Table 1 presents the clinical and
demographic data for each diagnostic group.
We found a main effect of diagnosis on depressive symptoms
[F(2, 206) = 14.5; P < 0.001] (Fig. 1). There was no main effect of
sex [F(2, 206) = 0.8; P = 0.39], the sex × diagnosis interaction was
not significant [F(2, 206) = 2.2; P = 0.12], and none of the
covariates was significant. Because there was no main effect or
interaction with sex, we again conducted the post hoc analyses
after removing sex from the model. Tukey-Kramer pairwise
comparisons found significantly higher depressive symptoms in
MCI compared with healthy controls (P < 0.01) and in AD
compared with healthy controls (P < 0.0001), but not in MCI
compared with AD (P = 0.10).
Emotional contagion and depressive symptoms were signifi-
cantly but very weakly correlated [r(214) = 0.15; P < 0.05], which
suggests that these measures evaluate possibly related, yet largely
distinct, aspects of emotional functioning.
Neuroimaging. Whole-brain voxel-based morphometry (VBM)
analyses revealed that higher levels of emotional contagion were
associated with smaller volume in bilateral middle temporal
gyri and right inferior temporal gyrus, superior temporal gyrus,
temporal pole, anterior hippocampus, and parahippocampal
gyrus (P < 0.001, uncorrected). The only cluster that survived
correction for multiple comparisons was one that included right
inferior, middle, and superior temporal gyri (PFWE< 0.05). See
Table 2 for the T scores and significance levels for each region;
Fig. 2 displays the statistical maps. Higher emotional contagion
was not associated with larger volume in any brain regions. A
follow-up region of interest analysis of bilateral amygdala
revealed a small cluster in the right amygdala for which smaller
volume was associated with higher emotional contagion [T =
3.25; Montreal Neurological Institute (MNI) peak, 26, −4, −24
(P < 0.001); cluster size, 80 mm3(P < 0.001, uncorrected)].
When we repeated the whole-brain analysis and also included
depressive symptoms as an additional nuisance covariate, the re-
sults were largely the same as those from the first analysis. Smaller
volume in a cluster that included right inferior, middle, and supe-
rior temporal gyri (T = 5.12; MNI peak, 70, −14, −8; cluster size,
uncorrected) and left middle temporal gyrus (T = 4.22; MNI peak,
be associated with higher emotional contagion. Two additional
clusters in right angular gyrus (T = 3.63; MNI peak, −58, −6, −16;
size, 576 mm3; P < 0.001, uncorrected) and left inferior frontal
gyrus (T = 3.65; MNI peak, −52, 30, 18; size, 232 mm3; P < 0.001,
uncorrected) werealso associated with higher emotional contagion
in this analysis. A small cluster in right anterior hippocampus
continued to be associated with higher emotional contagion (T =
3.2; MNI peak, 26, −8, −16; cluster volume, 56 mm3; P < 0.001,
In a whole-brain analysis that examined whether smaller brain
volume was also associated with higher levels of depressive
higher than in healthy controls (CTL). (A) Raw emotional contagion (IRI
Personal Distress subscale) and (B) depressive symptom (GDS) scores for the
CTL (n = 111), MCI (n = 62), and AD (n= 64) groups. Komogorov-Smirnov
tests of normalcy indicated that there was a normal distribution of emo-
tional contagion scores in MCI (P > 0.05) and AD (P > 0.05). (C) Emotional
contagion and (D) depressive symptoms, adjusted for age and education and
stratified by sex, were higher in patients than in healthy controls. Significant
main effects of diagnosis are denoted by *P < 0.01, **P < 0.001, and ***P <
0.0001. Error bars represent SEMs.
Emotional contagion and depressive symptoms in MCI and AD are
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symptoms, no regions emerged as being significantly associated
(P < 0.001, uncorrected).
Emotional contagion, a basic affective mechanism by which
emotions spread across individuals (37, 38), increased linearly in
MCI and AD. There were significant gains in emotional conta-
gion at each stage of disease progression (i.e., controls vs. MCI
and MCI vs. AD). Sex did not influence emotional contagion in
any diagnostic group. Consistent with previous studies, depressive
symptoms were also higher in the patients, with the most notable
escalation occurring between the control and MCI stages. Despite
these gains, in all groups the mean level of endorsed mood
symptoms remained in the range of minimal to mild depression.
As expected, there was a weak correlation between emotional
contagion and depressive symptoms, which suggests these mea-
sures primarily assess nonoverlapping components of emotional
behavior. Thus, our findings of heightened emotional contagion
in MCI and AD cannot be fully attributed to a more general
mood disorder but, rather, likely reflect a more specific change in
interpersonal emotional reactivity. Whole-brain structural MRI
analyses revealed that smaller volume in primarily right-hemisphere
temporal lobe structures was associated with greater emotional
contagion. Tissue loss in these regions was not associated with
higher depressive symptomatology.
Alteration in the neural systems that support emotion detection
and emotion generation may accentuate emotional contagion in
MCI and AD. At the most rigorous statistical thresholds, smaller
right inferior, middle, and superior temporal gyri volume was as-
sociated with higher emotional contagion. At less stringent statis-
tical thresholds, smaller volume in other predominantly right-
hemisphere temporal lobe regions, including right temporal pole,
right anterior hippocampus, and right parahippocampal gyrus, in
addition to left middle temporal gyrus, was also associated with
higher emotional contagion. These regions are important for
a number of critical socioemotional abilities includingprocessingof
intention, theory of mind, faces, gaze, emotion, speech, sarcasm,
may interfere with comprehension of social nuances, especially in
situations in which cognitive demands are high.
The association we found between hippocampal atrophy and
higher emotional contagion is consistent with previous animal
and human studies that have found an inhibitory role of the
hippocampus in emotion. Smaller hippocampal volume has been
associated with emotional reactivity and amygdala hyperactivity
(28, 47) not only in AD (16, 48) but also in various neuropsy-
chiatric disorders including major depressive disorder (49, 50),
bipolar disorder (51, 52), and posttraumatic stress disorder (53,
54), among others. The hippocampus, which is densely populated
with glucocorticoid receptors, is hypothesized to inhibit emo-
tional responses to stressful stimuli via negative feedback of the
hypothalamic-pituitary-adrenal axis (55). Chronic negative emo-
tional reactivity and its accompanying autonomic-neuroendo-
crine cascade potentiate amygdala-dependent behavior [e.g.,
anxiety-like behavior (56), aggression (57), and fear conditioning
(58)] by inducing reorganization of medial temporal circuitry
(i.e., increased dendritic branching in the amygdala and simpli-
fication of dendritic branching in the hippocampus) (56, 59, 60).
Although most studies suggest that heightened emotional re-
activity causes hippocampal simplification and amygdalar elab-
oration at the neuronal level (59), there is evidence from human
(61) and animal (62, 63) studies that smaller hippocampal vol-
ume at baseline and laboratory-induced hippocampal lesions
can precede the behavioral manifestations of hyperemotionality.
Rats with hippocampal lesions, for example, exhibit behavioral
changes suggestive of hyper-reactivity; are more responsive to
mild stressors, including foot-shock (63) and cage relocation
(62); and have increased glucocorticoid responding to aversive
events (64, 65). In humans harboring an underlying AD process,
heightened emotional reactivity may exacerbate disease progression
Table 1. Demographic information for each diagnostic group
Clinical and demographic informationControlsMCI AD Total
Sex, % female
Age, mean (SD)
Education, mean (SD)
Mini-Mental State Examination, mean (SD)
IRI Personal Distress, mean (SD)
Mini-Mental State Examination total scores, IRI Personal Distress subscale scores, and GDS total scores are
presented for each diagnostic group.
*Different from controls at P < 0.05.
†Different from MCI at P < 0.05.
‡104 controls, 58 individuals with MCI, and 52 individuals with AD had available GDS data.
higher levels of emotional contagion (cluster volume >150 mm3)
Volume loss in predominantly right-hemisphere temporal regions is associated with
Anatomical regionCluster volume (mm3)xyz Maximum T-score
Right middle temporal gyrus
Right inferior temporal gyrus
Right superior temporal gyrus
Left middle temporal gyrus
Right temporal pole
Right anterior hippocampus
Right parahippocampal gyrus
Montreal Neurological Institute coordinates (x, y, z) given for maximum T-score for each cluster. All results are
significant at P < 0.001, uncorrected.
*Results significant at PFWE< 0.05.
†Regions that were included in the cluster immediately above.
Sturm et al.PNAS Early Edition
| 3 of 6
through a positive feedback loop in which the autonomic-neuro-
endocrine cascade further potentiates hippocampal degeneration
and salience network hyperexcitability in some individuals.
Volume change in predominantly right-hemisphere temporal
lobe regions was associated with emotional contagion, a finding
that is consistent with theories that emphasize the role of the
right hemisphere in emotion (66). However, our results suggest
that neurodegeneration of distinct right temporal lobe regions
may have different influences on emotion. InMCI and AD,early
neurodegeneration of the right hippocampus may result in dys-
regulation of emotional contagion through loss of negative
feedback of emotional reactivity secondary to release of emotion-
generating structures in the salience network (14) or loss of glu-
cocorticoid receptors (55) or interneurons (65, 67) that help to
regulate visceromotor affective responsivity. As atrophy progresses
to temporal structures that are important for socioemotional
and inferior temporal cortex) (68), degradation of social-cognitive
their appraisal of socioemotional stimuli. Although formal studies
of emotion recognition have found both preservation (69, 70) and
part, on task difficulty and severity of cognitive impairment (71).
Similar to theories of emotion that propose that affective stimuli
can activate the amygdala via direct (i.e., a rapid pathway by which
stimuli activate the amygdala via projections from the thalamus) or
indirect (i.e., a slower pathway by which stimuli are first processed
by cortex before activating the amygdala) routes (73), individuals
with MCI and AD may retain their social graces and interpersonal
relationships by relying on preserved automatic emotion-sharing
mechanisms (i.e.,direct pathway) despitedegeneration ofcortical
systems important for more sophisticated socioemotional stimu-
lus processing (i.e., indirect pathway).
In this study, we used the Personal Distress subscale of the
IRI, a valid index of emotional contagion (74). Although emo-
tional contagion may motivate prosocial behaviors that are
essential for survival in social groups (36), if too strong, conta-
gion may overwhelm the observer and interfere with helping and
consolation (44). Although Personal Distress scores are a proxy
measure of emotional contagion, and higher scores may in part
reflect generally heightened anxiety and lack of emotional con-
trol (75) in the patient groups, our findings suggest that in MCI
and AD there may be particular dysregulation of emotional re-
activity in social contexts. Other psychological factors, including
decreased self-efficacy and waning autonomy, may also contrib-
ute to patients’ hyper-reactivity in stressful social situations.
There are some limitations to this study that should be con-
sidered. First, MCI is a heterogeneous syndrome, and although
most individuals with MCI show neuropathological changes that
are consistent with an underlying AD process (76), not all will
progress to develop dementia, and some may have a neurode-
generative disease other than AD. Thus, our assumption that the
MCI group represents an intermediate stage between the cog-
nitive health and AD may be flawed, although it is likely that
a subset, if not the majority, of patients in the MCI group have
Second, we found higher levels of depressive symptoms in MCI
and AD than in healthy controls, a finding that is consistent with
previous studies (5–7). Given that themean level of endorsedmood
symptoms was in the range of minimal depression for all diagnostic
groups, this may have affected our ability to detect a relationship
possible that by using a more specific measure of affective func-
tioning (emotional contagion, which was based on informant ob-
able to detect associations with specific patterns of brain atrophy.
Third, by using a structural neuroimaging technique, we did
not detect positive associations (which here would reflect either
less tissue loss or even possible growth) between emotional
contagion and brain volume in our sample. We did not find ev-
idence that larger volume in any salience network structures
(e.g., anterior cingulate cortex or frontoinsula) was associated
with higher emotional contagion. Rather, in a region of interest
analysis, we found evidence that smaller volume in the right
amygdala, a structure important for emotional reactivity, was
also associated with higher emotional contagion. Although at-
rophy in salience network structures, including the amygdala, is
common even early in AD, relative amygdala preservation has
been associated with higher levels of anxiety and irritability (77),
and there is heightened amygdala activation to faces in AD even
when controlling for volume loss (48). Our findings, together
with previous studies, suggest that higher salience network acti-
vation levels and stronger connectivity strength, rather than in-
creased volume, may be a more sensitive indicator of emotional
upregulation in this disease. Future work that uses other methods,
such as functional neuroimaging, will be important to better un-
derstanding how specific network enhancement relates to height-
ened emotional contagion.
Heightened emotional contagion in MCI and AD reflects a bi-
ological change in the neural systems that support and inhibit
emotion. We found a linear increase in emotional contagion, an
evolutionarily conserved affect mechanism by which others’ emo-
tions resonate in an observer, in MCI and AD that was associated
with atrophy in predominantly right-hemisphere temporal lobe
regions with known roles in emotion detection and generation. In
MCI and AD, relative preservation (or hyperconnectivity) (14)
among salience network and emotion-generating systems may
result in intensification of automatic affect-sharing, and gains in
emotional contagion may lead to enhanced interpersonal con-
nections and warmth despite deterioration of regions that support
higher-order social-cognitive appraisal processes. Emotional con-
tagion may be a useful mechanism by which to measure affective
change in animal models of AD because it is an ecologically valid
index of empathic reactivity that presents in other species and can
be elicited in laboratory settings.
Y = -12
Y = -4
Z = -10X = 27
with higher emotional contagion (IRI Personal Distress subscale score) when
controlling for age, education, sex, diagnosis, field strength, and total in-
tracranial volume (n = 237). Smaller volume in right inferior, middle tem-
poral, and superior temporal gyri was associated with higher emotional
contagion after correction for type 1 error (PFWE< 0.05). At less stringent
statistical thresholds, smaller volume in left middle temporal gyrus, right
temporal pole, right anterior hippocampus, and right parahippocampal
gyrus were also associated with higher emotional contagion (P < 0.001,
uncorrected). Color bars represent T scores (hot, PFWE< 0.05 according to
study-specific permutation analysis; blue, P < 0.001, uncorrected; T > 3.13
and cluster size > 150 mm3). Results are overlaid on a DARTEL-derived
template of 50 older healthy controls.
T-score maps of brain areas for which smaller volume is associated
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| www.pnas.org/cgi/doi/10.1073/pnas.1301119110Sturm et al.
Materials and Methods
Participants. Two hundred thirty-seven participants (111 healthy controls, 62
individuals with MCI, and 64 individuals with AD) participated in the present
study. All participants gave their informed consent for participation in the
study. All procedures were approved by the Committee on Human Research
at the University of California, San Francisco. All participants underwent
a multidisciplinary diagnostic evaluation that included a neurological ex-
amination, neuropsychological testing, laboratory studies, and structural
MRI. Healthy controls were recruited from advertisements and were free of
current or previous neurological or psychiatric disorders. MCI was diagnosed
according to modified diagnostic criteria (78) and included amnestic, exec-
utive, and multidomain MCI because individuals who are younger and are in
the early stages of AD may have primary deficits in cognitive domains other
than memory (79). AD was diagnosed according to standard research criteria
(1). The Mini-Mental State Examination (80) was given to all participants to
screen for cognitive dysfunction. See SI Materials and Methods for more
details about the diagnostic criteria.
Emotional Measures. Emotional contagion. Informants completed the IRI and
rated participants on their current behavior. Informant ratings of personality
and behavior in patients with dementia have been demonstrated to be
a reliable measure of functioning (81). The IRI is a psychometrically robust,
multidimensional measure that is composed of four subscales that evaluate
distinct components of empathy (44, 75). Our measure of emotional con-
tagion was the Personal Distress subscale (scores range from 7 to 35, with
higher scores reflecting greater emotional contagion), which measures the
degree to which individuals experience anxiety and discomfort when they
are exposed to the negative emotions of others (e.g., “Being in a tense
emotional situation scares him/her”). Informants rated participants on each
item on a scale of 1 (does not describe participant well) to 5 (describes
participant very well).
Depressive symptoms. As a comparison measure, participants completed the
Geriatric Depression Scale (GDS) (82). Participants were asked to report on
their mood over the last 2 wk by responding yes or no to a series of ques-
tions (scores from 0 to 30, with higher scores reflecting greater levels of
depression). The GDS classifies depressive symptoms as mild (0–10 points),
moderate (11–20 points), or severe (21–30 points).
Analyses. The groups differed significantly in age [F(2,237) = 5.74; P < 0.01]
and education [F(2,237) = 3.91; P < 0.05]. Thus, we adjusted for these vari-
ables in all analyses. The groups did not differ in their proportions of men
and women [χ2(2, n = 237) = 4.61; P = 0.10]. However, because sex can in-
fluence emotion and empathy (83–85), we examined sex as a factor in our
analyses. See Table 1 for means and SDs of these demographic variables.
We conducted separate 2 (sex: men, women) × 3 (diagnosis: control, MCI,
AD) analyses of covariance (controlling for age and education) on emotional
contagion and depressive symptoms. Post hoc Tukey-Kramer analyses were
run to examine pairwise differences while correcting for multiple compar-
isons. To determine the degree to which emotional contagion and depressive
symptoms measured the same underlying construct, we also conducted bi-
variate correlations between these two measures.
Neuroimaging. Participants underwent 1.5-T, 3-T, or 4-T research-quality
structural MRI within 5 mo of completing the IRI, as described in SI Materials
and Methods. Structural neuroimaging analyses using images collected
across different modes of hardware have shown that the downstream
effects of using images collected across different modes of hardware are
minimal (86) and, thus, are unlikely to cause artifacts at the level of strict
Preprocessing. Structural T1 images were visually inspected for movement ar-
tifact; corrected for bias field; segmented into gray matter, white matter, and
parametric mapping (SPM)5 (88). The diffeomorphic anatomical registration
through exponentiated lie algebra (DARTEL) toolbox was used to warp each
participant’s image to a template created from 50 additional older healthy
control participants to optimize intersubject registration (89). Gray and white
matter maps were then summed, and these images were smoothed with
an 8-mm full-width at half-maximum Gaussian kernel. See SI Materials and
Methods for more details about the preprocessing.
Analyses. We conducted whole-brain VBM analyses to correlate emotional
contagion with combined gray/white matter structural maps. Results were
considered significant at P < 0.001, uncorrected. One thousand permutation
analyses using combined peak and extent thresholds were run to derive
a study-specific error distribution to determine the one-tailed T threshold
for multiple comparisons correction at PFWE< 0.05 (90). Permutation analysis
is a resampling approach to significance testing by which a test statistic is
compared with the null distribution derived from the present study’s data
set, and thus is an accurate representation of type 1 error at P < 0.05 across
the entire brain (91). In the VBM analyses, we included age, education, sex,
diagnosis (0 = control, 1 = MCI, and 2 = AD to account for disease pro-
gression), field strength, and total intracranial volume (to account for in-
dividual differences in head size). We next performed two follow-up
analyses to further explore the neural correlates of emotional contagion.
First, we repeated our first analysis but restricted our search to bilateral
amygdala to determine whether we could detect an association between
emotional contagion and amygdala volume. Second, we conducted an addi-
tional whole-brain analysis of emotional contagion, but here also included GDS
total score as a covariate (age, education, sex, diagnosis, field strength, and
total intracranial volume were also included, as in the first analysis). Finally, we
conducted a whole-brain analysis using depressive symptoms (i.e., GDS total
score) as our independent variable of interest (age, education, sex, diagnosis,
field strength, and total intracranial volume were included as nuisance cova-
riates as described earlier) to determine whether emotional contagion and
depressive symptoms were related to atrophy in overlapping neural systems.
Images were overlaid with MRIcron (http://www.mccauslandcenter.sc.edu/
CRNL/) on an average brain based on the gray and white matter templates
used for DARTEL warping.
ACKNOWLEDGMENTS. We thank Drs. Stephen Wilson (www.neuroling.
arizona.edu) and Benno Gesierich for their assistance with the neuroimag-
ing processing and analyses. This project was supported by National Institutes
of Health, National Institute on Aging, Grants P50AG023501, P01AG019724,
1R01AG029577, 1K23AG040127, and P50-AG023501-08S1 and Larry L. Hillblom
Foundation Grants 2002/2J, 2007/2I, and P0047697.
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| www.pnas.org/cgi/doi/10.1073/pnas.1301119110Sturm et al.
Supporting Information Download full-text
Sturm et al. 10.1073/pnas.1301119110
SI Materials and Methods
Participants. Mild cognitive impairment was diagnosed according
to modified diagnostic criteria (1): (i) significant complaint in one
or more cognitive domains, (ii) meaningful decline in one or
more cognitive domains over the last 5 y, (iii) difficulty in the
cognitive domain relative to one’s peers, (iv) does not meet
criteria for dementia, and (v) absence of other conditions that
could account for the cognitive decline. Alzheimer’s disease was
diagnosed according to standard research criteria and was
characterized by a gradual decline in memory and at least one
other cognitive domain that resulted in functional impairment.
The Mini-Mental State Examination scores of the healthy con-
trol and mild cognitive impairment groups were in the normal
range; the mean score for the Alzheimer’s disease group was in
the mild range of impairment.
Neuroimaging. Image acquisition. Images were acquired on a 1.5T
Siemens Magnetom VISION system (Siemens, Iselin, NJ) at the
San Francisco Veterans Administration Hospital, equipped with
a standard quadrature head coil, using a magnetization prepared
rapid gradient echo (MPRAGE) sequence [164 coronal slices;
slice thickness, 1.5 mm; field of view (FOV), 256 × 256 mm2;
matrix, 256 × 256; voxel size, 1.0 × 1.5 × 1.0 mm3; repetition time
(TR), 10 ms; echo time (TE), 4 ms; flip angle, 15°]; on a 3.0 Tesla
Siemens (Siemens, Iselin, NJ) TIM Trio scanner equipped with
a 12-channel head coil located at the University of California,
San Francisco, Neuroscience Imaging Center using volumetric
MPRAGE (160 sagittal slices; slice thickness, 1.0 mm; FOV, 256 ×
230 mm2; matrix, 256 × 230; voxel size, 1.0 × 1.0 × 1.0 mm3; TR,
2,300 ms; TE, 2.98 ms; flip angle, 9°); and on a 4T Bruker MedSpec
system at the San Francisco Veterans Administration Hospital
with an 8-channel head coil controlled by a Siemens Trio console,
using an MPRAGE sequence (192 sagittal slices; slice thickness,
1 mm; FOV, 256 × 224 mm2; matrix, 256 × 224; voxel size, 1.0 ×
1.0 × 1.0 mm3; TR, 2,840 ms; TE, 3 ms; flip angle, 7°).
Preprocessing. In all preprocessing steps, statistical parametric
mapping (SPM)5 default parameters were used, with the ex-
ception of using the light clean-up procedure in the morphological
filtering step. Default tissue probability priors (voxel size, 2.0 ×
2.0 × 2.0 mm3) of the International Consortium for Brain Map-
ping were used. Segmented images were visually inspected for
adequate gray-white segmentation. Seven patients with AD had
MRIs that were initially visually inspected but were excluded from
the analyses because of movement artifact and poor scan quality.
1. McKhann G, et al. (1984) Clinical diagnosis of Alzheimer’s disease: Report of the
NINCDS-ADRDA Work Group under the auspices of Department of Health and Human
Services Task Force on Alzheimer’s Disease. Neurology 34(7):939–944.
Sturm et al. www.pnas.org/cgi/content/short/13011191101 of 1