![Brain areas with altered ReHo the in-love group (LG) and ended-love group (ELG). Significantly increased regional homogeneity (ReHo) was found in the left dorsal anterior cingulate cortex (dACC; -6,18,33) in the LG (LG > SG), but reduced ReHo was found in the left caudate nucleus [ELG < SG, (-15,9,21); ELG < LG, (-18,9,24)] and the right caudate nucleus [ELG < SG, (18,9,2); ELG < LG, (18,12,18)] in the ELG. All resultants were corrected by FDR correction (P < 0.05). *Coordinates in MNI space.](https://www.researchgate.net/profile/Fred-Doleire-Uquillas/publication/272181685/figure/fig2/AS:272048144515079@1441872740820/Brain-areas-with-altered-ReHo-the-in-love-group-LG-and-ended-love-group-ELG_Q320.jpg)
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ORIGINAL RESEARCH ARTICLE
published: 13 February 2015
doi: 10.3389/fnhum.2015.00071
Love-related changes in the brain: a resting-state functional
magnetic resonance imaging study
Hongwen Song1†, Zhiling Zou1*†, Juan Kou1,Yang Liu1, Lizhuang Yang2, Anna Zilverstand 3,
Federico d’Oleire Uquillas 3and Xiaochu Zhang 2,4, 5 *
1Faculty of Psychology, Southwest University, Chongqing, China
2CAS Key Laboratory of Brain Function & Disease, School of Life Sciences, University of Science and Technology of China, Anhui, China
3Icahn School of Medicine at Mount Sinai, NewYork, NY, USA
4CAS Center of Medical Physics andTechnology, University of Science and Technology of China, Anhui, China
5School of Humanities and Social Science, University of Science andTechnology of China, Anhui, China
Edited by:
John J. Foxe, Albert Einstein College
of Medicine, USA
Reviewed by:
Inga D. Neumann, University of
Regensburg, Germany
Rosalyn J. Moran, Virginia Tech, USA
*Correspondence:
Xiaochu Zhang, CAS Key Laboratory
of Brain Function & Disease, School
of Life Sciences, University of
Science and Technology of China,
Hefei, Anhui 230027, China
e-mail: zxcustc@ustc.edu.cn;
Zhiling Zou, Faculty of Psychology,
Southwest University,
Chongqing 400715, China
e-mail: zouzl@swu.edu.cn
†These authors have contributed
equally to this work and shared first
authorship.
Romantic love is a motivational state associated with a desire to enter or maintain a
close relationship with a specific other person. Functional magnetic resonance imaging
(fMRI) studies have found activation increases in brain regions involved in the processing
of reward, motivation and emotion regulation, when romantic lovers view photographs of
their partners. However, not much is known about whether romantic love affects the brain’s
functional architecture during rest. In the present study, resting state functional magnetic
resonance imaging (rsfMRI) data was collected to compare the regional homogeneity
(ReHo) and functional connectivity (FC) across an “in-love” group (LG, N=34, currently
intensely in love), an “ended-love” group (ELG, N=34, ended romantic relationship
recently), and a “single” group (SG, N=32, never fallen in love). Results show that:
(1) ReHo of the left dorsal anterior cingulate cortex (dACC) was significantly increased in
the LG (in comparison to the ELG and the SG); (2) ReHo of the left dACC was positively
correlated with length of time in love in the LG, and negatively correlated with the lovelorn
duration since breakup in the ELG; (3) FC within the reward, motivation, and emotion
regulation network (dACC, insula, caudate, amygdala, and nucleus accumbens) as well
as FC in the social cognition network [temporo-parietal junction (TPJ), posterior cingulate
cortex (PCC), medial prefrontal cortex (MPFC), inferior parietal, precuneus, and temporal
lobe] was significantly increased in the LG (in comparison to the ELG and SG); (4) in
most regions within both networks FC was positively correlated with the duration of
love in the LG but negatively correlated with the lovelorn duration of time since breakup
in the ELG. This study provides first empirical evidence of love-related alterations in
brain functional architecture. Furthermore, the results shed light on the underlying neural
mechanisms of romantic love, and demonstrate the possibility of applying a resting-state
fMRI approach for investigating romantic love.
Keywords: romantic love, resting state fMRI (rsfMRI), regional homogeneity (ReHo), functional connectivity (FC),
dorsal anterior cingulate cortex (dACC), nucleus accumbens, temporo-parietal junction (TPJ), posterior cingulate
cortex (PCC)
INTRODUCTION
Romantic love, a very old topic, has been recorded in the poetry,
songs, stories, myths, and legends of human civilization for 1000s
of years (Jankowiak and Fischer, 1992;Baumeister et al., 1993).
It has been regarded as the inspiration for some of the most
extraordinary achievements of mankind (Bartels and Zeki, 2000),
and plays an important role in human survival, reproduction,
development, and evolution (Fisher, 1998).
Within the last century, romantic love has also become a topic
of interest for scientists. Psychologists, for example, define roman-
tic love as a motivational state associated with a desire to enter or
maintain a close relationship with a specific other person (Aron
and Aron, 1991;Cacioppo et al., 2012;Diamond and Dickenson,
2012). Love has also been shown to play a role in mediating reward
and goal-directed motivation (Cacioppo et al., 2012;Diamond and
Dickenson, 2012). It can alter cognition and behavior, such as
promoting intensely focused attention on the preferred individ-
ual, accompanied by euphoria, craving, obsession, compulsion,
distortion of reality, emotional dependence, personality changes,
and risk-taking (Peele and Brodsky, 1975;Clark and Mills, 1979).
Romantic love is thus a complex sentiment, involving emotional,
cognitive, and behavioral components (Sternberg, 1986;Hazan
and Shaver, 1987).
In recent years, researchers have devoted increasing attention
to the neurobiological substrates and neurological processes of
romantic love. Bartels and Zeki (2000) published the first func-
tional magnetic resonance imaging (fMRI) study investigating the
brain of a person looking at a photograph of someone whom
they love. Many other researchers have further studied the pat-
tern of brain activity of those who are in love using similar tasks
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Song et al. Love-related changes in the brain at rest
(Bartels and Zeki, 2000,2004;Aron et al., 2005;Ortigue et al.,
2007;Acevedo and Aron, 2009;Fisher et al., 2010;Xu et al., 2011).
Reviews of these studies conclude that love is accompanied by
significantly increased activation in brain regions such as the
ventral tegmental area (VTA), medial insula, anterior cingulate
cortex (ACC), hippocampus, nucleus accumbens (NAC), caudate
nucleus, and hypothalamus. At the same time, deactivations can be
found in the amygdala, prefrontal cortex (PFC), temporal poles,
and temporo-parietal junction (TPJ; Zeki, 2007;de Boer et al.,
2012;Diamond and Dickenson, 2012;Tarlaci, 2012). Cacioppo
et al. (2012) have suggested that romantic love-related brain
regions can be divided into subcortical and cortical brain networks
where the former mediates reward, motivation, and emotion reg-
ulation, and the latter mainly supports social cognition, attention,
memory, mental associations, and self-representation.
However, it remains unclear whether romantic love also affects
the functional architecture of the brain. After Biswal et al. (1995)
proposed that functional connectivity (FC) can be studied using
resting state functional magnetic resonance imaging (rsfMRI),
Raichle et al. (2001) proposed the use of rsfMRI for investigat-
ing the brain when no specific task is pursued. Compared to
task-fMRI, rsfMRI is a tool for exploring the intrinsic functional
architecture of the brain (Fox and Raichle, 2007;Van Den Heuv e l
and Hulshoff Pol, 2010;Chou et al., 2012;Lee et al., 2013). This
approach helps avoid potential confounds and limitations encoun-
tered in task-based approaches (e.g., practice, ceiling or floor
effects, or differential performance levels; Di Martino et al., 2008).
RsfMRI thus provides promising opportunities for investigating
the functional topology of the brain and has been widely used to
study differences between populations, too (Fox and Raichle, 2007;
Van Den Heuvel and Hulshoff Pol, 2010).
Most rsfMRI studies have adopted FC to examine the cor-
relations and dynamics between brain networks. FC is defined
as the correlation of spontaneous blood oxygen level-dependent
(BOLD) signals between spatially remote regions (Aertsen et al.,
1989;Friston et al., 1993). This measure describes the relationship
between neuronal activation patterns of anatomically separated
brain regions and networks (Van Den Heuvel and Hulshoff Pol,
2010). FC has been widely used to study clinical populations such
as schizophrenia (Lynall et al., 2010), Parkinson’s disease (Stof-
fers et al., 2008), autism spectrum disorder (Koshino et al., 2008),
depression (Greicius et al., 2007), and substance abuse and depen-
dence (Liu et al., 2010). However, FC provides little information
about local features of spontaneous brain activity observed in
individual regions.
In contrast, Regional Homogeneity (ReHo) is a local mea-
surement of FC, defined as the temporary similarity between a
given voxel and its neighbors (Zang et al., 2004). In this method,
Kendall’s coefficient of concordance (KCC) (Zang et al., 2004)
is used to measure the correlation between the time series of
a given voxel and its nearest neighbor voxels in a voxel-wise
way. ReHo is a validated measure of brain functioning, mea-
suring the synchronized oscillatory activity in the cerebral cortex
that is essential for spatiotemporal coordination and integration
of activity in anatomically distributed but functionally related
neural elements (Van Rooy et al., 2005). Neuronal synchroniza-
tion is also hypothesized to underlie the efficient organization of
information processing in the brain (Buzsáki and Draguhn, 2004),
facilitating the coordination and organization of information pro-
cessing across several spatial and temporal ranges (Fox et al.,2005).
In the past years, ReHo has been used to study a variety of popu-
lations including patients suffering from schizophrenia (Liu et al.,
2006), Parkinson’s disease (Wu et al., 2009), autism spectrum dis-
order (Paakki et al., 2010;Shukla et al., 2010), and depression (Yao
et al., 2009).
Given that romantic loveis a motivational state (Aron and Aron,
1991;Cacioppo et al., 2012;Diamond and Dickenson, 2012) and
that there are many specific psychological and behavioral changes
in romantic lovers (such as intensely focused attention on a pre-
ferred individual, obsession, and risk-taking; Peele and Brodsky,
1975;Clark and Mills, 1979) as well as facilitation of cognitive
behavior (Bianchi-Demicheli et al., 2006;Ortigue et al., 2007), it is
not strange to assume that being in love may affect the underlying
functional architecture structure of the involved brain regions. In
the present study, we computed both ReHo and FC from rsfMRI
data to investigate these proposed alterations in functional brain
architecture in romantic lovers.
MATERIALS AND METHODS
ETHICS STATEMENT
This study was approved by the Ethics Committee of Southwest
University. Written informed consent was obtained from all par-
ticipants. All participants were informed that their participation
was completely voluntary and that they may withdraw themselves
at any time. All participants were over 18 years of age.
PARTICIPANTS
One hundred healthy college students were enrolled in the study.
All participants were recruited from Southwest University (SWU,
Chongqing, China) by flyers and Internet advertisement. They
were interviewed at the beginning of the study procedure regarding
previous romantic relationships and demographic characteris-
tics. The participants were divided into three groups according
to their previous romantic relationship: (1) the “in-love” group
(LG; N=34), consisting of individuals currently intensely in
love; (2) the “ended-love” group (ELG; N=34), consisting of
individuals who had recently ended a close romantic relationship
and were not currently in love; and (3) the “single” group (SG;
N=32), consisting of individuals who had never fallen in love
with anyone.
There were no significant differences in family income, per-
sonal monthly expenses, age, or years of education (P>0.1)
among either of the three groups (Tab l e 1 ). The length of time
in love of participants in the LG was between 4 and 18 months
(12.21 ±3.33). In the ELG, duration since the last romantic rela-
tionship breakup was between 2 and 17 months (10.41 ±2.97),
while the length of relationship before breaking-up was 4–
39 months (15.12 ±9.91). All participants were of heterosexual
orientation.
SELF-RATED QUESTIONNAIRES
The Passionate Love Scale [PLS; Hatfield and Sprecher, 1986] was
used to measure the status of passionate/romantic love in the LG.
The PLS has been previously used in a sample of Chinese college
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Song et al. Love-related changes in the brain at rest
Table 1 |Economic status, demographic, and romantic relationship status of participants.
LG (In-love group)
(N=34, 16 females)
SG (Single group)
(N=32, 14 females)
ELG (Ended-love group)
(N=34, 15 females)
FP
Mean SD Mean SD Mean SD
Family income (RMB/months) 4.10 ×1037.04 ×1024.04 ×1036.22 ×1024.04 ×1036.82 ×10 20.1 0.91
Monthly expenses (months) 7.35 ×10278.32 7.41 ×10286.7 7.40 ×10263.72 0.05 0.95
Age (years) 21.23 2.45 21.4 1.9 21.15 2.1 0.13 0.88
Years of education (years) 13.23 2.45 13.4 1.92 13.15 2.1 0.12 0.89
Intensity of the love (PLS scores) 104.21 10.58
Length of time in-love (months) 12.21 3.33 12.11 9.91
Lovelorn duration since breakup
of romantic relationship (months)
10.41 2.97
LG, participants who were intensely in love; SG, participants who had never fallen in love with someone; ELG, participants who had just ended a romantic relationship
recently and were not currently in-love. PLS, Passionate Love Scale.
students (Xu et al., 2011;Yin et al., 2013). Average PLS score in the
LG was 104.21, and SD was 10.58.
SCANNING ACQUISITION AND IMAGE PREPROCESSING
All imaging data were acquired using a 3T Siemens scanner
(Siemens Medical, Erlangen, Germany) at the Brain Imaging
Research Center of Southwest University. Resting state fMRI
(rsfMRI) data were acquired using a T2∗-weighted echo-planar
imaging sequence [time repetition (TR) =2000 ms; time echo
(TE) =30 ms; flip angle =90◦; field of view (FOV) =220 mm;
Matrix =64 ×64, 32 slices; 3 mm slice thickness; voxel
size =3.4 mm ×3.4 mm ×3 mm]. For each participant 242
contiguous EPI functional volumes were collected during one run
of 8 min and 4 s. Participants were instructed to lie in the scan-
ner with eyes closed while thinking of nothing, and remaining
still, relaxed, and awake throughout the scanning session (Hao
et al., 2013). Additionally, high-resolution T1-weighted spin-echo
images were collected (TR/TE =1900 ms/2.52 ms; flip angle =9◦;
FOV =256 mm; Matrix =256 ×256; 1 mm slice thickness, 176
slices; voxel size =1mm×1mm×1mm).
Imaging data were analyzed by Statistical Parametric
Mapping software (SPM8; http://www.fil.ion.ucl.ac.uk/spm/
software/spm8/) using two processing toolkits [the Data Process-
ing Assistant for Resting-State fMRI (DPARSF; Chao-Gan and
Yu-Feng, 2009); and the resting-state fMRI data analysis Toolkit
(REST; Song et al., 2010)]. Prior to processing, the first five func-
tional volumes of each session were discarded to allow for scanner
stabilization. Cerebrospinal fluid (CSF), and the white matter sig-
nals were removed by classifying them as nuisance variables so
as to reduce the effect of head motion and non-neural BOLD
fluctuations (Fox et al., 2005;Kelly et al., 2008). In the present
study, we used white matter (white.nii), CSF (csf.nii), and the
whole brain activity signal to perform a matrix multiplication to
obtain the signal of the white matter and CSF (Chao-Gan and
Yu-Feng, 2009). Data preprocessing using DPARSF consisted of:
(1) slice-timing correction using Fourier interpolation to correct
for differences in slice acquisition time; (2) 3D motion correction
using least-squares alignment anda3translational and 3 rota-
tional parameter linear transformation to correct for inter-scan
head motion [movement threshold for translation (x,y,z direc-
tion) was set at 2 mm; rotational movement (roll, pitch, yaw)
threshold was set at 2◦]; (3) spatial normalization to a stan-
dard template (Montreal Neurological Institute) with resampling
to3mm×3mm×3 mm; (4) spatial smoothing using a
4-mm full-width-at-half-maximum (FWHM) Gaussian kernel;
and (5) temporal band-pass filtering (0.01–0.08 Hz) to reduce
low-frequency drift and high-frequency physiological noise.
DEFINITION OF SEED REGIONS
Based on previous results in task-fMRI studies of romantic love
(Bartels and Zeki, 2000,2004;Aron et al., 2005;Ortigue et al.,
2007;Fisher et al., 2010;Xu et al., 2011), we selected ten regions
of interest (ROIs) as seed regions for the FC analysis. Each ROI
was a small 10 mm centered sphere (Tab l e 2). To ensure that each
ROI included only voxels of one brain region, these spheres were
additionally masked with a corresponding region-mask to exclude
neighboring anatomical structures.
FUNCTIONAL CONNECTIVITY (FC) ANALYSIS
The correlation maps for these seed regions were produced by
computing correlation coefficients between the mean time series
of each ROI and the time series of all other brain voxels for each
participant. Correlation coefficients were converted to z-values
using Fisher’s r-to-ztransform to improve normality. In order
to compare the FC across the three groups, a one-way Analy-
sis of Variance (ANOVA) was calculated for each ROI based on
the individual maps. Group analyses were thresholded using false
discovery rate (FDR) correction (P<0.05).
ReHo ANALYSIS
Following procedures from a previous study (Chao-Gan and
Yu-Feng, 2009), a whole brain map of ReHo values was calcu-
lated, voxel-wise, for each participant before spatial smoothing.
In order to reduce the effects of variability across participants,
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Song et al. Love-related changes in the brain at rest
Table 2 |Seed regions of interest (ROIs) and their MNI coordinates.
ROI (radius, 10 mm) Left Right Reference
xyzxyz
dACC −6 18 32 6 33 23 Bartels and Zeki (2000,2004),Aron et al. (2005),Fisher etal. (2010)
Caudate −12 6 15 15 9 21 Bartels and Zeki (2000,2004),Aron et al. (2005),Ortigue et al. (2007),Xu
et al. (2011),Acevedo etal. (2012)
Insula −33 15 −15 30 18 −15 Bartels and Zeki (2004),Ortigue et al. (2007),Fisher et al. (2010),
Acevedo etal. (2012)
TPJ −57 −42 18 51 −39 24 Bartels and Zeki (2000,2004),Ortigue et al. (2007,2010 )
PCC −6−45 21 8 −44 24 Bartels and Zeki (2000,2004),Aron et al. (2005),Ortigue et al. (2007),
Fisher et al. (2010),Acevedo etal. (2012)
the ReHo value of each voxel was normalized by dividing
it by the mean whole-brain ReHo value of each participant
(Chao-Gan and Yu-Feng, 2009;Wu et al., 2009;Liu et al., 2011;
Zhang et al., 2012). The individual ReHo maps were compared
across the three groups by using a ANOVA with FDR correction
(P<0.05).
CORRELATION ANALYSIS BETWEEN rsfMRI AND BEHAVIOR
To investigate brain–behavior relationships we conducted simple
regression analyses, regressing either ReHo/FC on the length of
time in love (in the LG) or the lovelorn duration since breakup
(in the ELG). Individual ReHo z-values were extracted from small
ROI spheres (6 mm radius) placed where we found differences in
the previous ReHo analyses across the three groups. The individual
FC z-values were extracted from ROIs based on results from the
comparison of FC across groups (FDR, P<0.05).
RESULTS
REGIONAL HOMOGENEITY (ReHo) DIFFERENCES BETWEEN GROUPS
Results showed that ReHo was significantly increased in the LG in
the left dorsal anterior cingulate cortex (dACC) [LG >SG, peak
coordinates (–6,18,33); LG >ELG, peak coordinates (–6,18,30)].
Furthermore, significant reduced ReHo was found in the ELG
in the left caudate nucleus [LG >ELG, peak coordinates (–
15,9,21); SG >ELG peak coordinates (–18,9,24)] and right caudate
nucleus [LG >ELG, peak coordinates (18,9,21); SG >ELG, peak
coordinates (18,12,18)] (See Figure 1).
FUNCTIONAL CONNECTIVITY (FC) DIFFERENCES BETWEEN GROUPS
The between-group comparison results of FC showed that the LG
(in comparison to the SG) had significantly increased FC between
the dACC seed and insula, NAC, and amygdala; between the
insula seed and NAC, caudate nucleus, and amygdala; between
the caudate seed and dACC, and insula; between the TPJ seed
and ventromedial prefrontal cortex (vMPFC), and dorsal medial
prefrontal cortex (dMPFC); and between the posterior cingulate
cortex (PCC) seed and the inferior parietal lobe, MPFC, precuneus,
and temporal lobe (See Figure 2;Table 3).
In comparison to the ELG, the LG also showed significantly
increased FC between the dACC seed and insula; between the
caudate nucleus seed and insula; between the TPJ seed and vMPFC,
and dMPFC; and between the PCC seed and inferior parietal lobe,
MPFC, precuneus, and temporal lobe (See Ta b l e 4 ).
In comparison to the SG, the ELG showed significantly
increased FC between the dACC seed and insula, amygdala,
caudate nucleus, and NAC; between the caudate nucleus seed
and dACC, and insula; between the TPJ seed and vMPFC, and
dMPFC; between the PCC seed and inferior parietal lobe, MPFC,
precuneus, and temporal lobe (See Tab l e 5 ).
CORRELATION BETWEEN rsfMRI AND BEHAVIOR
Regression analyses showed that while ReHo of the left dACC (–
6,18,33) significantly increased with the length of time in love in
the LG, it was significantly decreased with the lovelorn duration
of time since breakup of romantic relationship in the ELG. Fur-
thermore, while ReHo of the bilateral caudate nucleus was not
correlated with the length of time in love in the LG, it was signif-
icantly positively correlated with lovelorn duration of time since
breakup in the ELG (Figure 3).
Regression analyses of FC and behavioral data showed that FC
(dACC–insula, dACC–amygdala, dACC–NAC, insula–amygdala,
insula–caudate, insula-NAC, TPJ–vMPFC, TPJ–dMPFC, PCC–
precuneus, PCC–inferior parietal lobe, PCC–MPFC) was signifi-
cantly positively correlated with length of time in love in the LG,
and significantly negatively correlated with the lovelorn duration
of time since breakup in the ELG (Figure 4).
DISCUSSION
Although previous task-fMRI studies have preliminarily identified
romantic love-related brain networks (Aron et al., 2005;Fisher
et al., 2010;Xu et al., 2011), it remained unclear whether romantic
love can affect the functional architecture of the brain. In the
present study, we computed both ReHo and FC using rsfMRI
data across three groups of participants (LG,“in-love” group who
were currently intensely in love; ELG, “ended-love” group who
recently ended a romantic relationship and were not currently in
love; and SG, “single” group who had never fallen in love with
anyone).
ReHo analysis results showed significantly increased ReHo of
the left dACC in the in-love group (LG >SG, LG >ELG). Fur-
thermore, the ReHo of the left dACC was positively correlated with
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Song et al. Love-related changes in the brain at rest
FIGURE 1 |Brain areas with altered ReHo the in-love group (LG) and
ended-love group (ELG). Significantly increased regional homogeneity
(ReHo) was found in the left dorsal anterior cingulate cortex (dACC;
−6,18,33) in the LG (LG >SG), but reduced ReHo was found in the left
caudate nucleus [ELG <SG, (−15,9,21); ELG <LG, (−18,9,24)] and the
right caudate nucleus [ELG <SG, (18,9,2); ELG <LG, (18,12,18)] in the
ELG. All resultants were corrected by FDR correction (P<0.05).
*Coordinates in MNI space.
the length of time in love in the LG, and was negatively correlated
with lovelorn duration in the ELG, suggesting that the ReHo of
the left dACC may be closely related to the state of falling in love.
At the same time, the ReHo of the bilateral caudate nucleus was
significantly decreased in ELG (ELG <SG, ELG <LG), and was
positively correlated with lovelorn duration in the ELG, suggest-
ing that ReHo of the caudate nucleus may be closely related to the
effects of ending a love relationship.
Results of FC showed that the lover group had significantly
increased FC (LG >SG, LG >ELG) within the reward, motiva-
tion, and emotion regulation brain network (including the dACC,
caudate nucleus, NAC, and insula) as well as in the social cog-
nition network (including the TPJ, PCC, mPFC, precuneus, and
inferior parietal lobe). Comparable to the ReHo analysis results
(in the left dACC), FCs in both networks were significantly posi-
tively correlated with the length of time in love in the LG, as well
as negatively correlated with lovelorn duration in the ELG, sug-
gesting that falling in love may also be associated with increased
connectivity within certain brain networks.
ROMANTIC LOVE AND THE REWARD, MOTIVATION AND EMOTION
REGULATION NETWORK
The ACC, caudate nucleus, amygdala, NAC, and insula
are core components of the brain systems that play an
important role in the processing of sensory and emotional
information, reward, and motivational processes (Mogen-
son et al., 1980). In the present study, we found significant
increased FC in the LG (LG >SG, LG >ELG) between
the ACC, caudate nucleus, amygdala, NAC, and insula. This
may imply that romantic love may change the function of
the reward, motivation, and emotion regulation brain net-
work.
The dACC plays a key role in monitoring conflict through
information processing, and compensatory adjustments in cogni-
tive control (Botvinick et al., 2004). In fact, some researchers have
found increased activation in the ACC individuals with greater
social insight and maturity (Lane et al., 1998;Bush et al., 1999).
Bartels and Zeki (2000) suggested that the dACC is implicated
in states of happiness, interoception (i.e., attention to one’s own
emotional state), and also in social interactions that involve assess-
ing one’s own and other people’s emotions and states of mind.
For example, Aron et al. (2005) found that length of time in
love is positively correlated with dACC activation when watching
photographs of a romantic partner.
The caudate nucleus is highly innervated by dopaminergic neu-
rons that originate mainly from the VTA and substantia nigra pars
compacta (SNc). The caudate nucleus is associated with reward
detection, expectation, representation of goals, and integration of
sensory inputs (Aron et al., 2005;Lauwereyns, 2006).
The amygdala is mainly responsible for processing information
related to fear, sadness and aggression, and mediating emotional
learning (Dalgleish, 2004). Activation level in the amygdala has
been shown to decrease when participants view photos of their
sweetheart (Bartels and Zeki, 2000,2004;Aron et al., 2005;Xu
et al., 2011). Furthermore, the NAC, a brain area coinciding with
cortical areas rich in dopamine and oxytocin receptors, is an
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Song et al. Love-related changes in the brain at rest
FIGURE 2 |Altered functional connectivity (FC) pattern in comparison
across the three groups. Images of FC demonstrates differences in
resting-state FC between groups (A) LG >SG, (B) ELG >SG,
(C) LG >ELG (see Tables 3–5 for complete results). For each
comparison, the top row shows the FC pattern of the left hemisphere
and the bottom row shows the right hemisphere. L, left; R, right. All
resultants were corrected by FDR correction (P<0.05). *Coordinates in
MNI space.
important part of the reward pathway that plays a central role
in the visual perception of pleasant stimuli (Aharon et al., 2001;
Sabatinelli et al., 2007). It is involved in both natural and abnormal
reward processes (Breiter et al., 2001;Knutson et al., 2005;Baler
andVolkow,2006;Knutson and Wimmer, 2007;Cooper and Knut-
son, 2008). Within the context of love,the recruitment of the NAC
is therefore consistent with notions of romantic love as ‘a desire
for union with another’ (Hatfield and Rapson, 1993;Acevedo et al.,
2012).
The insula has been ascribed a role in representing subjective
feelings, attention, cognitive choices, intentions, time percep-
tion, awareness of sensations, movements (Farrer and Frith, 2002;
Critchley et al., 2004;Tsakiris et al., 2007), the visual image of the
self (Devue et al., 2007), subjective expectations (Seymour et al.,
2004;Preuschoff et al., 2008), and the trustworthiness of other
individuals (Craig, 2002). Studies of romantic love report that
the activity in the insula is increased when participants view their
romantic partner’s picture (Bartels and Zeki, 2004;Ortigue et al.,
2007;Fisher et al., 2010).
Previous research has demonstrated that spatially remote brain
regions do not function independently, but rather, interact with
one another during cognitive processing. For example, when indi-
viduals engage in a reinforcement learning paradigm relating to
judging the positive or negative value of visual stimuli both the
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Song et al. Love-related changes in the brain at rest
Table 3 |Significant regions in the comparison of functional
connectivity (FC) between the LG and SG.
Seed ROI Location of
naximum
intensity voxel
Cluster
size
(Voxels)
MNI coordinates
x y z z-value
LG>SG
Left dACC
Left insula 221 −36 0 0 4.93
Right insula 305 33 12 −15 5.22
Left NAC 28 −12 6 −12 3.67
Left amygdala 49 −21 0 −12 3.75
Right amygdala 51 −24 −6−18 4.04
Right dACC
Left insula 335 −36 −3−9 6.09
Right insula 337 39 0 −12 5.82
Right NAC 28 9 9 −12 4.25
Left amygdala 80 −30 −3−21 5.33
Right amygdala 95 −27 0 −18 4.3
Left insula
Left caudate 89 −12 18 −3 3.93
Right caudate 65 15 21 −6 4.16
Left amygdala 80 −21 0 −12 3.79
Right insula
Left NAC 20 −12 9 −12 1.44
Right NAC 25 12 9 −9 2.51
Left caudate 160 −12 −9 18 4.23
Right caudate 188 18 21 −3 3.49
Left amygdala 59 −27 −6−18 5.34
Right amygdala 69 30 −9−12 4.07
Left caudate
Right dACC 58 9 21 24 5.09
Left insula 50 −45 6 3 4.25
Right insula 73 48 9 −6 4.9
Right caudate
Right dACC 34 12 27 21 3.6
Left TPJ
Left vMPFC 39 −12 63 −3 4.89
Right vMPFC 73 9 63 −12 4.21
Left dMPFC 362 0 30 39 5.61
Right dMPFC 305 6 30 39 5.01
Right TPJ
Left vMPFC 103 0 60 −12 4.3
Right vMPFC 93 12 54 −12 4.31
Left dMPFC 365 −3 27 39 5.4
Right dMPFC 192 12 45 24 4.29
(Continued)
Table 3 |Continued
Seed ROI Location of
naximum
intensity voxel
Cluster
size
(Voxels)
MNI coordinates
x y z z-value
Left PCC
Left inferior
parietal
342 −27 −48 51 5.01
Right inferior
parietal
109 30 −48 54 4.97
Left MPFC 142 0 −3 54 3.96
Right MPFC 377 6 27 54 4.11
Left precuneus 560 −3−57 66 5.57
Right
precuneus
515 9 −60 57 4.53
Left temporal
lobe
531 −45 −63 −9 5.15
Right temporal
lobe
772 48 −15 −18 5.79
Right PCC
Left inferior
parietal
238 −39 −57 60 4.83
Right inferior
parietal
80 30 −48 54 4.15
Left MPFC 63 0 3 54 4.04
Left precuneus 387 −6−63 66 6.06
Right
precuneus
327 6 −60 51 4.27
Left temporal
lobe
254 −60 −12 9 5.4
Right temporal
lobe
270 51 −51 −21 5.19
LG <SG
None
NAC, nucleus accumbens; MPFC, medial prefrontal cortex; vMPFC, ventral
medial prefrontal cortex; dMPFC, dorsomedial prefrontal cortex. FDR correc-
tion (P <0.05) for multiple comparisons, MNI coordinates (x,y,z) for the most
significant voxel in a cluster.
amygdala and the NAC are involved in signal processing, which is
then passed on to the insula (Reynolds and Zahm, 2005;Paulus
and Stein, 2006). Unconditioned and conditioned sexual incen-
tive cues are also known to be processed in the caudate nucleus,
which expects, detects, and represents the reward values of the
external stimulus, and outputs them to the insula (Cacioppo et al.,
2012). The control of a goal-directed behavior will involve both
the insula, representing awareness, and the ACC, representing
the control of directed effort (Craig, 2009). Thus, increased FC
between these regions in a group of lovers may be the result of
frequent efforts to monitor their own emotional state, as well as
their lovers’ emotional state, monitoring conflicts while adjusting
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Song et al. Love-related changes in the brain at rest
Table 4 |Significant regions in the comparison of FC between the LG
and ELG.
Seed ROI Location of
maximum
intensity voxel
Cluster
size
(Voxels)
MNI coordinates z-value
xyz
LG >ELG
Left dACC
Left insula 34 −39 6 0 2.81
Right insula 78 36 18 0 3.62
Right dACC
Left insula 18 −45 6 0 2.39
Right insula 44 36 24 0 3.02
Left caudate
Left insula 13 −36 0 12 3.18
Right insula 29 39 0 15 3.49
Left TPJ
Right dMPFC 189 6 27 48 3.22
Right TPJ
Left vMPFC 72 9 66 6 3.15
Left dMPFC 39 −12 18 48 2.66
Right dMPFC 37 12 30 42 2.27
Left PCC
Right inferior
parietal
35 36 −48 48 2.38
Left MPFC 47 −3 36 27 3.31
Left precuneus 195 −12 −78 48 2.69
Right
precuneus
290 6 −60 48 3.35
Right temporal
lobe
116 5 4 −66 21 2.86
LG<ELG
None
FDR correction (P <0.05), MNI coordinates (x,y,z) for the most significant voxel
in a cluster.
cognitive strategies in order to resolve conflicts so as to maintain
their romantic relationship.
ROMANTIC LOVE AND THE SOCIAL COGNITION NETWORK
Our findings show that the LG had significantly increased
FC compared to the SG and ELG between the TPJ seed and
vMPFC, and dMPFC; and between the PCC seed and infe-
rior parietal, MPFC, precuneus, and temporal lobe. Moreover,
FC was significantly positively related to the length of time
in love in the LG. These regions are part of a social cogni-
tion network, which contains brain areas activated during social
interaction and areas involved in general cognition and atten-
tion. Regions activated during social interaction include the
TPJ, vMPFC, and dMPFC. This network has been consistently
associated with social, moral and ‘theory of mind’ tasks (the
Table 5 |Significant regions in the comparison of FC between the ELG
and SG.
Seed ROI Location of
maximum
intensity voxel
Cluster
size
(Voxels)
MNI coordinates z-value
xyz
ELG >SG
Left dACC
Left insula 76 −36 −9 9 3.57
Right insula 77 36 −24 21 4.64
Left NAC 20 −12 9 −12 2.53
Left amygdala 29 −24 −6−12 3.7
Right amygdala 41 30 −6−12 5.41
Right dACC
Left insula 226 −36 −6−6 4.47
Right insula 241 33 −18 −18 5.29
Left amygdala 30 −27 −6−15 3.46
Right amygdala 48 27 −6−12 3.85
Left caudate
Left dACC 35 −6 21 30 3.24
Right dACC 43 6 18 27 5.35
Left insula 139 −39 −15 0 4.81
Right insula 121 39 15 −3 5.26
Left TPJ
Left dMPFC 152 −6 48 48 5.61
Right dMPFC 73 12 51 39 5.28
Right TPJ
Left vMPFC 32 −357−15 4.26
Left dMPFC 134 −9 57 36 4.76
Right dMPFC 82 12 48 42 4.7
Left PCC
Left inferior
parietal
75 −54 −48 42 5.29
Right inferior
parietal
42 57 −42 48 4.48
Left MPFC 280 −3 36 36 5.61
Right MPFC 261 3 57 36 5
Left precuneus 37 −15 −39 66 4.43
Left temporal
lobe
165 −42 −15 −3 5.38
Right temporal
lobe
421 57 −18 −15 5.37
LG<ELG<SG
None
FDR correction (P <0.05), MNI coordinates (x,y,z) for the most significant voxel
in a cluster.
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Song et al. Love-related changes in the brain at rest
FIGURE 3 |Correlation between ReHo and the length of time in-love
(in LG) or the lovelorn duration since the breakup of romantic
relationship (in ELG). (A) depicts ReHo in the left caudate nucleus (–18, 9,
24), which was significantly positively correlated with the length of time
since the romantic relationship breakup in ELG; (B) shows ReHo in left
dACC (–6,18,33), which was significantly negatively correlated with the
length of time in love of LG; (C) demonstrates ReHo in the right caudate
nucleus (18,12,18), which was significantly positively correlated with the
length of time since the romantic relationship breakup in ELG; (D) shows
ReHo of left dACC (–6,18,30), which was significantly positively correlated
with the length of time since the romantic relationship breakup of ELG.
*Coordinates in MNI space.
FIGURE 4 |Correlation between FC and length of time in-love (in LG) and
the lovelorn duration since breakup of romantic relationship (in ELG). (A)
depicts the significant positive correlation between FC and the length of time
in-love in LG; (B) shows the significant negative correlation between FC and
the lovelorn duration since the breakup of romantic relationship in ELG.
Intensity of FC was extracted from ROIs (small sphere of 6 mm radius, the
center coordinates are listed in Table 3) based on the results of the FC
comparison between the LG and SG (FDR, P<0.05). The absolute value of
the correlation coefficient increases gradually from the center to the
circumference. Numbers represent the correlation coefficient, and the colors
represent the corresponding brain regions. These are only the results of the
right hemisphere. All correlations shown were significant (P<0.05).
ability to determine other people’s emotions and intentions)
(Frith and Frith, 1999;Brunet et al., 2000;Gallagher and
Frith, 2003), and has been associated with social trustworthi-
ness (Winston et al., 2002), facial expressions (Winston et al.,
2002), moral judgment (Greene and Haidt, 2002;Moll et al.,
2002), and attention to one’s own emotions (Lane et al., 1997;
Gusnard et al., 2001). Brain regions generally involved in social
cognition include the PCC and inferior parietal and mid-
dle temporal cortices, which play a role in cognitive atten-
tion, and short-and long-term memory (Beauregard et al., 1998;
Maddock, 1999;Cabeza and Nyberg, 2000;Buckner et al.,
2008).
Frontiers in Human Neuroscience www.frontiersin.org February 2015 |Volume 9 |Article 71 |9
Song et al. Love-related changes in the brain at rest
DOPAMINE, OXYTOCIN, VASOPRESSIN, AND ROMANTIC LOVE
Our results show increased FC between subcortical regions in
lovers (between the caudate nucleus, NAC, amygdala, and insula),
areas closely related to the mesolimbic dopaminergic system. The
mesolimbic dopaminergic system is suggested to be a mechanism
by which humans and other mammals enact behaviors that main-
tain and protect their pair-bonds (Winslow et al., 1993;Sue Carter
et al., 1995;Wang et al., 1997;Aragona et al., 2003). Dopamine has
also been shown to play an important role in the romantic love of
humans (Acevedo et al., 2012).
The VTA is centrally placed in a wider motivational/reward
network associated with behaviors necessary for survival (Camara
et al., 2009). It is considered a central platform for pleasurable
feelings and pair-bonding (Ortigue et al., 2010). The NAC has
been implicated in the interaction between the neurotransmitter
dopamine and the neuropeptide oxytocin (Liu and Wang, 2003).
Both oxytocin and vasopressin have been shown to be crucially
involved in romantic love and bonding (Kendrick, 2000;Fisher
et al., 2006;Gonzaga et al., 2006). Oxytocin is released during
sexual activity and mating, and may be the neurochemical mecha-
nism for the anxiolytic effect of mating (Waldherr and Neumann,
2007). Recently, Rilling etal. (2012) suggested that both oxytocin
and vasopressin were associated with increased FC between amyg-
dala and the anterior insula, possibly enhancing the amygdala’s
ability to elicit visceralsomatic markers in order to guide decision-
making. The increased FC observed between subcortical regions
in lovers may therefore reflect the neurophysiological interaction
between oxytocin, dopamine, and/or vasopressin while in a state
of love.
EFFECT OF LOVELORN STATE ON BRAIN NETWORKS
Although we did not intentionally investigate the effect of lovelorn
in the present study, we found that ReHo of the bilateral cau-
date nucleus was significantly decreased in the ELG (ELG <SG,
ELG <LG) and was also correlated with the lovelorn duration
of time since breakup of romantic relationship in the ELG (not
correlated with the length of time in love in the LG).
As discussed before, the caudate nucleus is associated with
detection of reward, expectation, representation of goals, and
integration of sensory input (Aron et al., 2005;Lauwereyns,
2006). Deep brain stimulation of the caudate nucleus has been
shown to improve symptoms of anxiety disorder and major
depression (Aouizerate et al., 2004). Neurochemical studies have
demonstrated that these effects may be mediated by non-selective
corticotropic-releasing systems. Being in a relationship has been
associated with elevated CRF mRNA in the bed nucleus of the stria
terminalis in nerve fibers originating from the amygdal (Bosch
et al., 2008). Therefore, the caudate nucleus may be very impor-
tant for relieving symptoms of anxiety and depression. An elevated
FC between regions involved in the anxiety-relief system after
breaking up may be a sign of recovery.
LIMITATIONS
The chosen approach was a cross-sectional design, conducted
via a comparison across three independent subject groups. Fur-
ther longitudinal studies will be necessary to verify and extend
the findings of the present study. One challenge for longitudinal
studies of romantic love may be that romantic relationships are
not easily controlled inside a laboratory. Another possible lim-
itation of this study is that we do not know exactly whether
love-related alterations are adaptation, or maladaptation in lovers.
From an evolutionary perspective, romantic love can be seen as
a mechanism developed for choosing a partner that offers the
best chances for survival to the offspring (de Boer et al., 2012).
We therefore propose that love-related alterations in FC or ReHo
reflect this mechanism, as it is a correlate of the individuals’effort
when trying to maintain an important inter-personal relation-
ship. However, based on the present results we cannot directly test
this hypothesis. In future studies, cognitive and behavioral tasks
should therefore be employed to further investigate the relation-
ship between resting brain functional alterations and love-related
behaviors.
CONCLUSION
In summary, we calculated Regional Homogeneity (ReHo) and
functional connectivity (FC) using resting state functional mag-
netic resonance imaging (rsfMRI) data to investigate romantic
love-related brain functional topological changes. We found that
love-related alterations included increased ReHo of the left dACC
and increased FC within the reward, motivation, and emotion reg-
ulation network, as well as the social cognition network. We also
found decreased ReHo of the bilateral caudate nucleus related to
the ending of a romantic relationship.
This study provides the first empirical evidence of love-related
alterations in the underlying functional architecture of the brain.
Findings are in agreement with results from task-dependent
fMRI studies, and complement well the functional findings of
task-dependent fMRI studies. These results shed light on the
underlying neurophysiological mechanisms of romantic love by
investigating intrinsic brain activity, and demonstrate the possibil-
ity of applying a resting state approach for investigating romantic
love.
ACKNOWLEDGMENTS
We thank Jie Yin for technical assistance in brain imaging data col-
lection. This work was supported by grants from the National
Natural Science Foundation of China (31230032, 31171083,
31471071), the Fundamental Research Funds for the Central Uni-
versities of China (WK2070000033) and the 100 Talents Program
of The Chinese Academy of Sciences (BJ2070000047).
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Conflict of Interest Statement: The authors declare that the research was conducted
in the absence of any commercial or financial relationships that could be construed
as a potential conflict of interest.
Received: 25 September 2014; accepted: 28 January 2015; published online: 13 February
2015.
Citation: Song H, Zou Z, Kou J, Liu Y, Yang L, Zilverstand A, d’Oleire Uquillas F and
Zhang X (2015) Love-related changes in the brain: a resting-state functional magnetic
resonance imaging study. Front. Hum. Neurosci. 9:71. doi: 10.3389/fnhum.2015.00071
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