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Beyond Romance:
Neural and Genetic Correlates of Altruism in Pair-Bonds
1
Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA
93106, USA
2
Department of Psychology, University at Buffalo, Park Hall 208, Buffalo, NY 14260, USA
3
Department of Neurology, Einstein College of Medicine, 1300 Morris Park Ave., Room 117,
Corresponding author
Bianca P. Acevedo
Neuroscience Research Institute
University of California, Santa Barbara
Santa Barbara, CA 93106-5060
Email: Bianca.acevedo@lifesci.ucsb.edu
1
Abstract
Key words: altruism, emotion, empathy, oxytocin, vasopressin, ventral pallidum, pair-bonding,
fMRI
2
Pair-bonding, or monogamy, is the tendency to stay with one partner for mating, reproduction,
child-rearing, and attachment throughout life. In both humans and other monogamous species,
care of offspring, sharing of a nest (or cohabitation), aggression towards strangers, and highly
coordinated behaviors between male-female pairs such as the tendency to travel together (e.g.,
Curtis, Liu, Aragona, & Wang, 2006; Getz et al., 1981; Mendoza & Mason, 1986). Other
behaviors that characterize attachment bonds are caregiving and altruistic acts which are
thought to ultimately promote species fitness (Batson, 2011; deWaal, 2008; Preston & deWaal,
2011). It is proposed that altruism and its corresponding neural systems evolved for the care of
helpless offspring, but may also be observed in the aid of other kin and non kin recipients
(Preston, 2013).
Extensive research with voles and primates has established subcortical anatomical and
neurochemical correlates of pair-bonding (Bales et al., 2007; Carter, 1998; Lim et al., 2004a;
Lim et al., 2004b; Lim and Young, 2004 ), as well as empathy and consolation (de Waal, 1979;
Langford et al., 2006; Jeon et al., 2010; Burkett et al., 2016). Direct injections of hormones into
the brains of voles and receptor autoradiography showed that the density of oxytocin (OT) and
arginine vasopressin (AVP) receptors in the ventral pallidum (VP) differentiated pairs that
established partner preference after mating (Lim et al., 2004a; Lim et al., 2004b; Lim and
Young, 2004). Using c-fos and viral vector gene transfer methods, Lim and Young (Lim et al.,
2004b) identified the VP and nucleus accumbens (NAcc) as the critical brain regions mediating
monogamous behaviors. Studies with primates also established the VP as specifically active in
pair-bonds (Bales et al., 2007), and OT and AVP release in pair-bonds, including in long-term
3
Research suggests that the VP and NAcc are part of a social decision-making network
that is phylogenetically conserved, but variable, in vertebrates including fish (e.g., teleosts),
reptiles, and mammals (O'Connell and Hofmann, 2012). This putative social network, partially
identified in voles and primates, involves several other brain regions such as the septum,
(VTA), and ventromedial prefrontal cortex (vmPFC), thus including the reward system
(Johnson and Young, 2015; O'Connell and Hofmann, 2012). Studies with humans have
suggested that OT, AVP and some of these neural structures may also mediate maternal
attachment, pair-bonding, and complex social behaviors such as trust, eye contact, and increased
partner empathy during sex (Carter, 1998; Unkelbach et.al., 2008; Behnia et al., 2014; review
OT and AVP are important neurohormones as they control diverse functions, from water
balance and reproduction to attachment, pair-bonding, and social recognition (Insel, 2010;
Numan and Young, 2016; Meyer-Lindberg et al., 2011). OT and AVP are easy to administer
intranasally to humans, directly affecting the brain. Thus, a number of human functional MRI
(fMRI) studies have used this experimental approach for hormone delivery to examine OT’s
role in empathy, altruism, negative emotion, social reward, and parenting (Bartz et al., 2010;
Groppe et al., 2013; Hu et al., 2016; Riem et al., 2011). In mothers shown happy and sad infant
face images, intranasal OT was associated with increased activation in the insular cortex,
amygdala, and the globus pallidus (GP) (Rocchetti et al., 2014). These regions are involved in
emotion, response to emotional faces (Fusar-Poli et al., 2009), reward, and motor behavior
(Hong & Hikosaka, 2008). AVP also has been implicated in nurturing, and social and
cooperative behaviors (Brunnlieb et al., 2016; Stoop et al., 2015). A recent study examined
plasma levels of OT and AVP and found associations with activation of the amygdala in
4
response to negative images (Motoki et al., 2016). However, circulating plasma levels may not
reflect brain levels, and intranasal administration may not affect brain receptors equally or in all
regions of interest (Freeman et al., 2016). Also, intranasal OT’s effects can be modulated by
OT gene polymorphisms (Feng et al., 2015). Indeed, the use of gene polymorphisms to
determine the functional effects of OT and AVP has major advantages over intranasal
administration and plasma levels because the genetic markers are an endogenous variable that
can apply to brain substrates. Also, attention to gene polymorphisms in fMRI studies—
“imaging genetics”— may reduce the variability of experimental effects and localize
endogenous OT and AVP receptor function: OXTR rs53576 (Rodrigues et al., 2009) and
AVPR1a rs3 (Knafo et al., 2008), respectively. The marker rs53576 is a single-nucleotide
polymorphism (SNP) of the OT receptor gene (OXTR) that results in individuals having zero,
one, or two G alleles (versus A alleles). Individuals with a greater number of G alleles express
more emotional empathy (Buffone and Poulin, 2014; Uzefovsky et al., 2015), and exhibit less
stress and greater empathic accuracy when attending to others’ feelings (Rodrigues et al., 2009).
They also display more sensitive parenting behaviors (Bakermans-Kranenburg & van
IJzendoorn 2008) and greater responsiveness to infant crying (Riem et al. 2011), and also
engage in more charitable behaviors under conditions of perceived social threat (Poulin et al.,
2012). Meta-analyses of OXTR rs53576’s role in sociality showed that the homozygous variant
(GG alleles) was associated with greater empathic ability (Gong et al., 2017) and sociality (Li et
al., 2015). However, one meta-analysis suggested that effects were limited to general sociality
(18 studies), versus no significant results for sociality within close relationships (10 studies).
This may reflect the complexity of behaviors affected by OT, needing a range of behavioral
5
measurements in experiments. Also, most of the close relationship studies measured attachment
The marker AVPR1a rs3 is a section of an AVP 1a-type receptor gene (AVPR1a) that
can repeat a number of times, varying in length across individuals. Humans with longer versus
shorter versions of rs3 exhibit more cognitive empathy (Uzefovsky et al., 2015), greater
generosity towards strangers in laboratory studies (Knafo et al., 2008), and more stable pair-
bonds (Walum et al., 2008). We examined these alleles in the current study with pair-bonded
participants because they represent hormone activity associated with pair-bonding and pro-
Also, we investigated brain and gene interactions with self-reported altruism towards the
partner, measured with Agape scale (subscale from the Love Attitudes Scale (LAS); Hendrick
neurobehavioral mechanism for responding to others’ needs (Preston, 2013), even at a cost to
the self. It is thought to be adaptive, especially towards kin and close others (Wilson, 1975), as
it grants benefits to the “giver” such as increased mating success, social standing, and sharing of
resources (Fehr & Rockenbach; Trivers, 1971). Thus, “altruistic” traits would prevail as the
genes that they shared with kin would be passed on (Nowak, 2006). However, across species,
altruistic behaviors appear to occur without deliberation or expectation of reciprocity. Thus, the
The aim of this study was to identify subcortical regions associated with altruism in
human pair-bonds compared with strangers and familiar non-kin individuals. We also examined
whether the OXTR and AVPR1a genes, identified as being involved in pair-bonding (Walum et
al 2008; Acevedo et al., 2011), altruism (Knafo et al., 2008), and other complex social
behaviors (such as caregiving), activate corresponding subcortical sites that are rich in OT and
6
AVP 1a receptors. Thus, we measured for the first time in early-stage, marital pair-bonds the
subcortical neural correlates of altruism (measured with the Agape scale) and OXTR and
AVPR1a gene variants. While being scanned, participants viewed face images of a partner that
were selected for evoking feelings of romantic love; and in a separate session they viewed
happy and sad (as well as neutral) face images of the partner and a stranger to evoke empathy.
Because only 13 participants returned for a second scan, we investigated similarities across time
and thus report replications. We predicted that OXTR rs53576 (G alleles) and AVPR1a rs3
with the VP, NAcc septum, amygdala and midbrain due to their role in social behaviors,
emotion response, and binding sites for OT and AVP. We also predicted that these associations
would be present to a greater extent for individuals reporting greater feelings of altruism
towards the partner, and would be stronger (or unique to) associations in response to partner
Method
Participants
Participants provided informed consent and received payment in accordance with the
IRB procedures of the University of California, Santa Barbara (UCSB) and Albert Einstein
ages 22-33 (M =27.4 years ±3.4) in first-time marriages (M relationship length = 5.8 years±2.9;
range 2-12), and with no children. The sample was comprised of 15 White, 2 Hispanic and 1
Asian individuals. All but two participants had a college-education and the mean household
income ranged from $16,000 to $110,000 (M=62,000±27,000). Before scanning, subjects were
contraindications. Thirteen participants (8 females, 6 White, 1 Asian and 1 Hispanic) ages 22-
7
33 (M age = 27.5±3.6 years, married M = 10.8months ±4.0) returned for a second scan 11.3±1.3
months (range 9.0-13.5 months) after the T1 scan (range), using identical procedures.
Procedure
Upon recruitment, all participants were interviewed to assess their relationship quality
and to determine appropriate highly familiar neutral controls. They also completed
questionnaires and visited the laboratory with their spouse, and at this time photographs of the
spouse were taken by the experimenter. Photos were rated by independent coders (matched to
participants for age and gender) to assess whether partner and controls did not differ
systematically with respect to facial attractiveness. During the scan, participants completed two
consecutive experimental sessions. The first (“romance”) condition was intended to elicit
feelings of “romantic love” using face pictures (self-selected by participants) of the spouse
while recalling romantic events. This procedure was verified in a previous study (Mashek,
2000) showing that face images elicited the most intense romantic love feelings. Participants
also viewed images of a self-selected familiar neutral acquaintance. For both conditions, each
face image was followed by a countback task, where participants were shown a 4-digit number
and instructed to mentally count back by 7s, to reduce carryover effects from viewing affective
facial images. All photos were digitized, according to standard procedures where only the face
was shown. Stimuli were displayed using Presentation software (Psychological Software Tools,
Inc., Pittsburgh, PA). This protocol has been used in previous fMRI studies of early-stage (Aron
et al., 2005; Xu et al., 2011, 2012) and long-term romantic love and marital satisfaction
(Acevedo et al., 200, 2012) using the Passionate Love Scale (Hatfield & Sprecher, l986).
The second (“empathy”) session was adapted from research on maternal responsiveness
to own-infant and other-infant facial cues (Strathearn et al., 2008). Participants are shown
happy, sad and neutral face images of one’s own versus other infants, and it has been used in
8
research on sensory processing sensitivity with adults measuring neural responses a partner’s
and strangers negative and positive affective facial expressions (Acevedo et al., 2014).
After each session, while participants were still in the scanner participants provided
emotion ratings for each image they viewed. After the scan, participants completed in-depth
“Exit Interviews” to confirm that they recalled events with the partner.
sub-scale (from LAS, Hendrick et al., 1998) measure of six love styles) which assesses selfless,
altruistic love towards a romantic partner. Sample items are, “I am usually willing to sacrifice
my own wishes to let my partner achieve his/hers” and “I would rather suffer myself than let my
partner suffer.” Participants also completed the Relationship Assessment Scale (Hendrick,
1988) for general relationship satisfaction and the Passionate Love Scale (PLS; Hatfield &
Sprecher, l986), 15-item version, assessing cognitive, emotional and physical symptoms of
passionate love. All scales were measured using 1-7 item Lickert-ratings.
Stimuli. For the “romantic love” condition, participants were shown face images of the
Partner and a highly familiar, neutral acquaintance (HFN) matched to the partner by age, sex,
and length of time known. For the “empathy” condition at T1 and T2, subjects were shown
happy and sad face images of the partner (taken by the experimenter during the laboratory
session) and a stranger’s face image (selected from the data base) matched to Partners’ for age,
sex, and ethnicity. At T2, the empathy condition also included neutral Partner and Stranger face
images.
Additionally, for the “empathy” condition, context descriptions were shown (see
Acevedo et al., 2014) prior to each face image because context plays an important role in
emotion processing (Gross & John, 2003), thus reducing cognitive ambiguity and enhancing
emotion-specific effects as suggested by emotion researchers (e.g., McRae et al. 2011). Each
9
face image was preceded by a corresponding contextual description, such as “Your partner is
feeling very happy because something wonderful has happened to them” or “Your partner is
feeling very sad and they are suffering because something terrible has happened to them.
fMRI task. For the romantic love condition, the fMRI task utilized an alternating block
design where subjects viewed alternating face images of the Partner versus HFN, interspersed
with a countback task. Participants were asked to recall events with each person (not sexual in
nature) while viewing the respective face image. Each stimulus was presented for 20-seconds,
for 9 repetitions (total 12 minutes). Identical procedures and stimuli were used at T1 and T2.
The fMRI task for the empathy condition consisted of a randomized block design such
that no two conditions could follow each other. At T1, the fMRI four conditions were shown:
partner happy, partner sad, stranger happy, and stranger sad. At T2, two targets were added to
measure within target emotion responses: partner neutral and stranger neutral. Each condition
included the following stimuli in sequential order: contextual description (6-s), face image (12-
s), and a countback task (12-s). Each trial was presented randomly six times. Immediately after
each scanning session (romantic love and empathy), participants provided emotion ratings.
Gene Analysis
Subjects provided saliva samples for DNA extraction via Oragene test tubes
using RealSNP and MassARRAY Assay Designer (Sequenom Inc). The protocol involved PCR
amplification of 10ng DNA using SNP specific primers followed by a base extension reaction
using iPLEX Gold chemistry (Sequenom Inc.). The final base extension products were treated
MassARRAY Analyzer Compact MALDI-TOF-MS was used for the data acquisition process
10
from the SpectroCHIP. The resulting genotypes were called using MassARRAY Typer
Analyzer v4.0 (Sequenom Inc.), and the number of G alleles was used as a continuous variable
in our analyses.
For the AVPR1a rs3 genotype, the number of repeat sequences was identified via
primer congregated to a fluorescent probe and amplified for detection using polymerase chain
reaction (PCR). Microsatellite fragment analysis of AVPR1a rs3 was conducted through
capillary electrophoresis (Sequenom, Inc.). For AVPR1a analysis, 6-FAM and HEX labeled
PCR products were mixed and analyzed in multiplex. Samples were denatured at 92°C for 2
minutes and then cooled to 4°C on a MJ Research PT-100 Peltier Thermal Cycler. Samples
were transferred to a 96-well sequencing plate and assigned well coordinates using Applied
Biosystems Foundation Data Collection Version 3.0. Electrophoresis of the samples was
performed with the Applied Biosystems 3130xl Prism Genetic Analyzer, using dye/filter set,
DS-30. The data was processed and analyzed using Applied Biosystems GeneMapper Software
Version 3.7. Control samples were sequenced to determine the repeat size based on total
fragment length. A left and right offset of 0.4 was used in the bin set parameter of the
GeneMapper software to set the limits for acceptable fragment migration for each repeat. The
number of repeat sequences was split at the median to designate each allele as “long” versus
“short,” and the number of long alleles was used as a continuous variable in our analyses.
A 3.0 T Siemens Trio with a 12-channel phased-array head coil was used for the
planar imaging sequence that is sensitive to BOLD contrast was used to acquire 37 slices per
repetition time (TR = 2000 ms, 3 mm thickness, 0.5 mm gap), echo time (TE) of 30 ms, flip
11
angle of 90 degrees, field of view (FOV) of 192 mm, and 64 x 64 acquisition matrix. Prior to
the whole-brain was obtained (TR =15.0 ms; TE = 4.2 ms; flip angle = 9 degrees, 3D
acquisition, FOV = 256 mm; slice thickness = 0.89 mm, acquisition matrix = 256 x 256).
Neurology). First, functional echoplanar images were realigned to the first volume, smoothed
with a Gaussian kernel of 6mm, and then normalized to the T1.nii image template. No
were created at T1 and T2 for the “romance” condition: Partner vs. HFN; and the “empathy”
condition: Partner Happy vs. Stranger Happy and Partner Sad vs. Stranger Sad; and T2 only
added: Partner Happy vs. Partner Neutral, Partner Sad vs. Partner Neutral, Stranger Happy vs.
Multiple regression data analysis. Second-level regression analyses were carried out to
estimate group brain activity during each condition: Partner (Happy or Sad), entering Agape
scores and genotype (either AVPR1a or OXTR). The effects of AVPR1a rs3and OXTR rs53576
were tested in separate models because the impact of these polymorphisms in OT and AVP
receptor function is still unclear, as OT and AVP sometimes bind to similar receptors making it
difficult to discern their distinct function and binding sites (Song & Albers, 2017). Results are
for each regression. For the purposes of this report, the significance of the negative versus the
positive correlations will not be discussed in detail. A brain response correlation, positive or
Region of interest (ROI) and whole-brain analysis. ROIs were based on previous
studies of empathy, emotion, OT, OXTR, AVP, and AVPR1a (Table 1). We adopted a false
12
discovery rate (FDR) for multiple comparisons correction (Genovese, Luzar & Nichols, 2002)
at p < .05. ROIs occupied a 3-10-mm radius with a 3-voxel minimum, depending on the size of
the brain area. For exploratory purposes, we conducted whole-brain analyses, at p < .001
(uncorrected for multiple comparisons), minimum spatial extent of > 5 contiguous voxels. We
do not report cluster size, because there are questions about the statistical significance of cluster
Neuroantomical identification. All regions were confirmed using the human brain
atlas by Mai, Majtanik and Paxionos (2016). The VP was examined further using the visible
high-iron concentrations that were shown in the GP and substantia nigra (SN) echo-planar
images of the fMRI data (Fig 1B,C). In vole studies, iron was also used in histological sections
Results
Descriptive Statistics
at T1 and T2 on a 1-7 scale, indicating high satisfaction for all participants. The RAS was
significantly correlated with AVPR1a rs3 long alleles (r = 0.6, p < .05).
Passionate Love Scale. Passionate Love Scale (PLS) scores: M = 5.9±0.7 at T1 and
5.8±1.0 at T2 on a 1-7 scale. The PLS was not significantly correlated with OXTR or AVPR1a.
Altruism in the pair-bond. Agape scores: M = 5.3± 0.7 at T1 and 5.3± 1.1 at T2 on a 1-
7 scale. Agape was significantly correlated with OXTR G alleles (r = 0.7, p < .05) and the PLS
Stimuli emotion ratings. Emotional ratings in the scanner right after viewing the faces
confirmed that the subjects felt emotions consistent with the partner’s, HFN’s, or stranger’s
facial emotional displays. T-tests confirmed that emotions were more intense for Partners
13
compared with Strangers (Figures and results reported in Acevedo et al., 2014). Below, we
For the romantic love condition, emotion ratings (on a 1 to 4 scale, 1= not at all and 4 =
a great deal) for the Partner: love at T1 (M=3.7±0.6) and T2 (M=3.6±0.7), indifferent at T2
(M=2.9±1.1). Only AVPR1a rs3 was significantly correlated with love scores for the Partner (r
= 0.6, p < .05). No significant correlations emerged for OXTR, altruism scores, or affective
For the empathy condition, emotion ratings (on a 1 to 4 scale, 1= not at all and 4 = a
great deal) for the Happy Condition, Partner: joy at T1 (M=3.9±0.4) and T2 (M=3.7±0.5),
(M=1.6±0.8) and excitement at T2, (M=1.3±0.5). For the Partner, altruism scores were
significantly correlated with friendship ratings (r = 0.6, p < .05), no significant correlations
emerged with OXTR or AVPR1a. For the Stranger, only AVPR1a rs3 was negatively correlated
T1 (M=3.5±0.6) and T2 (M=3.5±0.7). For the Partner, no significant correlations emerged with
significant correlations emerged with OXTR or AVPR1a, and with Partner altruism scores.
14
(M=3.1±1.2). No significant correlations emerged with OXTR, AVPR1a, or altruism scores for
Correlations across the various stimuli (happy or sad, partner or stranger) suggest that
pair-bonded individuals report stronger affective ratings in response to a partner’s happy or sad
events. Importantly, OXTR (G-alleles) was significantly correlated with altruism towards the
partner, while AVPR (long-alleles) was significantly correlated with love ratings for the partner.
sample were as follows: OXTR rs53576 (AA=1, AG=6, GG=6); AVPR1a rs3 (short=4,
short/long=6; long=3).
Neuroimaging Results
romantic thoughts and memories were evoked, subjects showed responses in the same area of
the right VP at both time points (Fig 1). However, the VP response was not significantly
correlated with OXTR rs53576 G alleles, AVPR1a rs3 allele length or Agape scores. Also post-
scanner affective ratings showed no significant correlations with Agape scores. As such, we did
not proceed with interaction analyses for this condition. Subjects showed other significant
romance responses at T1 and T2 in the VTA/SN, caudate nucleus, and hypothalamus (Table 2).
Empathy condition. Partner Happy or Sad vs. Neutral expression and Stranger
Happy or Sad vs. Neutral. Partner Happy or Sad vs. Stranger Happy or Sad.
rs53576 (G alleles) and Agape scores for both Happy and Sad Partner (versus Partner Neutral)
conditions showed significant responses in the left VP (multiple regression: Happy: r= .62,
p=.02; Sad: r=.64, p=.02, Fig. 2A-D, I; Table 3). The correlations showed negative or zero
neural responses for AA and AG allele participants, and zero or positive responses for GG allele
15
2
participants (Fig. 2I [2] = 4.28, p =
.12).
For the Happy Partner (versus Partner Neutral) condition, other significant activations
were shown in sub-regions of the NAcc (ventral striatum) adjacent to the VP (Fig. 2D), the
basolateral amygdala (Fig. 2E), septum (Fig. 2A), PAG (Fig. 2F); as well as for the Partner
For the Sad Partner (versus Partner Neutral) condition, effects were shown in the
amygdala in areas similar to and distinct from (i.e., the c. amygdala) that shown for the Happy
condition; however no significant subcortical activations were shown for the Sad Partner versus
Sad Stranger condition. Interestingly, for the Sad Partner condition, there was a negative
response in the VTA in association with OXTR rs53576 G alleles and altruism scores (Fig. 2G).
alleles) and Agape scores for the Stranger Happy (versus neutral) condition, were significant in
the right caudate, amygdala and the left hypothalamus. For the Stranger Sad (versus neutral)
condition, interactions of OXTR rs53576 (G alleles) and Agape scores were significant in the
bilateral amygdala and the right hypothalamus. Notably, for both Stranger Happy and Sad
conditions vs. Neutral (Fig. 2H), there was no activation in the VP, and activations did not
(long alleles) and Agape scores were significant in the left VP for the Sad Partner (versus
neutral) condition (multiple regression: r=.58, p=.04, Fig. 3C, D, and I; Table 4); for the Happy
Partner (versus neutral) interactions were significant in the medial part of the internal segment
of the left GP, adjacent to the VP (Fig. 3 A, B, and F). The VP showed negative or zero neural
response for shorter allele participants, and zero or positive response for longer allele
16
2
participants (Fig. 3I). There were no significant male/female differences [3] = 3.95, p =
.27). For both Happy and Sad Partner (versus neutral) conditions the interaction of AVPR1a rs3
and Agape scores were significant in the basolateral amygdala, bilaterally (Fig. 3E); as well as
on the left side for the Partner Happy versus Stranger Happy condition.
For the Sad Partner (versus neutral) condition, significant activation was shown in the
anterior basal hypothalamus and the central nucleus of the amygdala (Table 4); and deactivation
was shown in the median Raphe/VTA (Fig. 3G). The Partner Sad versus Stranger Sad condition
For the Happy Partner (versus neutral) condition, the interaction of AVPR1a rs3 and
Agape scores showed significant activations in the PAG (Fig. 3F), inferior colliculus and the
septum (Table 3); and deactivations were shown in the medial dorsal nucleus of the thalamus.
Altruism and AVPR1a interactions, stranger condition. For both Stranger Happy and
Sad (versus neutral) conditions, the interaction of AVPR1a rs3 long alleles and Agape scores
were not significant in subcortical regions; notably, there was no activation in the VP (Fig. 3H).
For the Happy Partner (versus neutral) condition and Happy Partner (versus happy
stranger), interactions of both OXTR rs53576 and AVPR1a rs3 with altruism scores were
significant in the left amygdala (lateral/basolateral area, Fig. 4A), and the VP, but in different
regions (Figs. 2A, 3A) OXTR rs53576 showed positive correlations within the VP and in the
adjacent NAcc; while for AVPR1a rs3, positive correlations were shown in the GP internal
segment, and not in the NAcc. Also, both Happy Partner (versus stranger and partner neutral)
interactions with OXTR rs53576 and Agape scores showed significant activations in the PAG
and septum/fornix, as well as the Happy Partner (versus neutral) AVPR1a rs3 interactions. In the
17
Happy Stranger condition both OXTR rs53576 and AVPR1a rs3 also showed significant
activation in the left basolateral amygdala. The interaction of AVPR1a rs3 with Agape scores
For the Sad Partner (versus neutral) condition, the interactions of both OXTR rs53576
and AVPR1a rs3 with Agape scores were significant in the left VP, basolateral
amygdala/entorhinal cortex (Figs. 2E, 3E) the left central amygdala (Fig. 4B), and the
entorhinal/parahippocampal area. and deactivations were shown in the VTA/ median Raphé
For the Partner Happy vs. Stranger Happy and Partner Sad vs. Stranger Sad interactions
with OXTR rs53576 or AVPR1a rs3 and altruism scores, there were fewer significant subcortical
activations in comparison with Partner emotion versus neutral conditions. Most notably, the VP
was not significantly activated for most of the Partner versus Stranger comparisons, except for a
the Partner Happy versus Stranger Happy condition at T2. Inspection of the time courses of the
responses suggested that there was a large enough neural response to the Stranger emotion
conditions, and more so for the Sad Stranger condition, which resulted in weaker effects for the
Discussion
The present study showed, for the first time, significant activation in the VP region of
the human brain in association with romantic and altruistic feelings among individuals in
established pair-bonds around the time of the wedding and one-year later. This effect was not
found in previous studies of early-stage romantic love (Bartels and Zeki, 2004), but was
reported in association with relationship length among newly in-love individuals (Aron et al.,
18
2005). Thus, as in other mammals, the VP appears to be part of a subcortical attachment
system.
The left VP showed a significant multiple correlation with altruism scores (Agape
scale), and OXTR rs53576 and AVPR1a rs3 in response to a partners’ distressed and joyful
facial images. We did not see VP activation in response to the Stranger emotion conditions
compared to the Neutral Stranger, but the effect was not entirely specific to the Partner as
Partner Sad versus Stranger Sad comparisons did not show significant activation in the VP.
However, in response to the Happy Partner versus Happy Stranger condition, the left VP did
show significant activation at T2. These findings lend support to research implicating the VP in
pair-bonding in rodents (Wang et al., 1998; Young & Wang, 2004) and primates (Bales, 2007;
Hinde 2016), but also show that this system is used for empathic and altruistic feelings for
strangers. This is consistent with theories suggesting that cooperative social bonds to
genetically unrelated individuals may have played a central role in the evolution of humans
(Boyd, Richerson, & Heinrich, 2011). However, for positive emotional stimuli we showed a
bias for the partner (versus the stranger), consistent with research showing preferential biases
for in-group altruistic motivations (Telzer et al., 2015), especially for groups with strong
motivational importance (Hackel, Zaki, & Bavel, 2017), as well as for self-positivity among in-
love individuals (Meixner & Herbert, 2018). Here we add to this body of work on altruism by
showing that in-group/out-group neural responsivity to a partner’s and stranger’s emotions may
also vary as a function of the individuals’ genotype and the emotional context of a situation.
The VP is part of a subcortical network that has been identified as important for
attachment and social behavior across mammalian species. We show that humans also utilize
this phylogenetically conserved system for pair-bonding and complex social behaviors, such as
altruism, which enhance fitness and survival of the species through cooperation and care
19
(Carter, 1998; Numan and Young, 2016; Brunnlieb et al., 2016; Wilson, 1975). These
processes are also critical for healthy pair-bonds as responsiveness to a partner’s emotional
events, both positive and negative, are associated with increased relationship satisfaction and
stability (Gable et al., 2004; Waldinger et al., 2004). Moreover, altruism (measured with the
Agape) was highest in established relationships compared to developing and dissolved ones
(Loup et al., 1991) and to a lesser extent for AVP (Young et al., 1999). Lim et al. (2004b)
behaviors in promiscuous male voles. Also, a study with humans showed that the same AVP1a
rs3 gene variant examined herein, showed significant associations with male pair-bonding
The VP is part of the subcortical, mesolimbic reward system whose afferents from the
NAcc, and efferents to the thalamus, suggest organization of responses for social decision-
making and responsivity (Numan & Young, 2016; Root et al., 2015). In addition, the NAcc,
VTA and SN were activated in this study, further implicating the reward, motivation system in a
vertebrate “social network” (Groppe et al., 2013; O'Connell and Hofmann, 2012; Stott and
Redish, 2014). In the present study we further characterized the function of these genetic and
hormonal markers, and the VP, as described in a large body of laboratory animal studies as well
as human studies on pair-bonding and romantic love, to now also include altruism in pair-bonds,
which involves “caregiving” and has been proposed to be evolutionarily rooted in the need for
Other brain areas implicated in pair-bonding, empathy and cooperation across species
were also identified herein in the context of empathic responding and altruism in pair-bonds
20
Notably, the septum and amygdala, known for their role in affective-processing (Davis &
Whalen, 2000) and social decision-making (Johnson and Young, 2015; O'Connell and
Hofmann, 2012) were significantly activated in response to partners’ affective images and in
association with OXTR and AVPR1a variants. The septum, for example, has been identified in
studies of monogamous voles (Liu, Curtis, and Wang, 2001), and is rich in OT and AVP
receptors, (Loup et al., 1991; Young et al., 1999). Also, it appears to process approach-related
behaviors in humans (Morelli et al., 2015). It’s also interesting to note that the amygdala and
connectivity between the VP and dorsolateral prefrontal cortex were shown in a study where
males were given intranasal administration of AVP and showed increased cooperation
It’s also important to note that although happy and sad partner face images elicited
significant activation of the amygdala in association with altruism scores, and with OXTR and
AVPR1a variants, activations were in anatomically distinct and overlapping areas. The results
are consistent with a meta-analysis showing that the central amygdala is specifically implicated
in responses to negative visual stimuli (Garcia-Garcia et al., 2016), as we show for the Sad
condition in Fig. 3B. Also, replication of the amygdala localization in correlation with the
AVPR1a rs3 variant and selfless love, as reported herein, supports research linking the AVPR1a
variant with human amygdala function in response to social/ emotional stimuli and cooperation
(Brunnlieb et al., 2016; Meyer-Lindenberg et al., 2009). Other studies have also shown that
altruism and charitable acts are associated with AVPR1a rs3 long alleles (Buffone and Poulin,
2014; Knafo et al., 2008; Poulin et al., 2012). The present results suggest that altruism in pair-
bonds (which may be characterized as responding to a partner’s needs, even at a sacrifice to the
21
However, negative and positive brain responses in the same regions varied across
individuals with AVPR1a rs3 long alleles. This is consistent with evidence that AVPR1a’s
effects may vary as a function of receptor binding sites, and may underlie variation in social
traits and disorders, such as autism and anxiety. Many of the activity effects were localized to
the left hemisphere, notably in the VP. Hemispheric effects are found in many fMRI studies,
and we have found a significant functional left-right difference in the VTA for early stage
romantic love: left side activity was correlated with facial attractiveness, while right side
activity was associated with passionate love scores (Aron et al., 2005). However, we do not
have enough data or information from the literature to speculate about the meaning of these
lateralized effects.
was in opposite direction for OXTR rs53576 as a function of G alleles (Fig 1J, 2J). The result is
interesting in light of the large literature on OT administration that implicitly assumes that OT
will work the same way for all recipients. If diverse OXTR genotypes differentially affect brain
and binding sites, then whether endogenous or exogenous, OT (as well as AVP and other
hormones that may be readily administered) may not work the same way for everyone. This is
consistent with evidence that OT administration can result in opposite behavioral effects among
individuals depending on attachment style, relationship status, and social context (Bartz et al.,
variant (homozygous GG) it was found to be correlated with general social behaviors, and not
romantic relationships (Li et al., 2015). For close relationships, the meta-analysis included a
conflict. Here, we also did not see VP activation in association with OXTR rs53576 for the
22
romantic partner condition, but we did see its significant activation in association with greater
self-reported altruism towards a romantic partner across happy and sad conditions, and to a
greater extent for OXTR rs53576 (G-alleles). Thus, it may be that this variant mediates complex
Limitations
Although these results are novel, multidisciplinary and expand our knowledge of neural
and behavioral functions related to OXTR and AVPR1a function with corresponding subcortical
neural targets for altruism in pair-bonds, further investigation is needed as our sample was
modest in size and mostly homogenous. Thus, future research may benefit from sampling
social/demographic backgrounds. Also, cortical effects and differences across time (requiring a
Although the sample size was modest, we reduced variability of the sample by recruiting
first-time newlyweds with no children. Also, the effect for the VP and other subcortical regions
was replicated for Partner empathy and the romantic partner conditions. Replication is the best
statistical test, and we can conclude with some confidence that the human VP is involved in
ultimately strengthens the attachment bond, and increases the fitness of the species. The genetic
and empathic response study meets only the minimum sample size (David et al., 2013; Friston,
2013) as only a subset of participants returned for the second scan (at this time we obtained the
conditions for both partners and strangers—thus providing evidence of effects for positive and
negative affect, as well as for close and non-kin relationships. Also, the VP correlations were
found within the same group for two genetic markers, replicating effects for two closely-related
23
hormone receptors. Further, the rationale for the ROIs, and especially for the VP, was very
strong as laboratory animal studies implicate functional effects of OT and AVP in the VP. In
sum, the regions and genes examined herein were hypothesis-driven, with a strong rationale of
established findings in a large body of animal research. Also, importantly, other brain regions
we report as activated in the brainstem replicated effects from other fMRI studies examining
OT’s and AVP’s effects on social behaviors (Groppe et al., 2013; Meyer-Lindenberg et al.,
2009; Riem et al., 2011). This field could certainly benefit from additional research as the
present findings do not establish the circuits identified herein, however they do provide a good
foundation for future experiments. It’s also noteworthy that this research applied an
challenges.
Conclusion
In summary, this research provides novel evidence for neural, behavioral, and genetic
factors underlying an evolved system for altruism in pair-bonds which may further sustain the
bond through attachment and fitness of the couple (Burkett et al., 2016; Carter, 1998; Lim et al.,
2004a; Lim et al., 2004b; Lim and Young, 2004; Williams et al., 1992). But also, these factors
appear to be at work in response to strangers. We show that associations with AVPR1a and
OXTR, and altruism activate key subcortical regions, such as the VP, accumbens, septum and
the amygdala, in the context of empathic/emotional responsiveness. These regions are critical
to pair bonds in other mammals and part of a vertebrate social network (O'Connell and
Hofmann, 2012). The use of these structures and hormones for social processes through
evolution appears to be conserved across highly social species, such as humans. Like other
vertebrates, key physiological systems for human pair-bonding may use the VP for attachment.
Also, AVP and OT binding in the VP may mediate emotion-driven, relationship and partner-
24
preserving behaviors. In addition, genetic variability was expressed by both increased and
decreased responses in the VP. Thus, genetic variation influences the direction of neural effects
in individuals reacting to the same stimulus type, helping to account for the observed variability
in the measurements of behavioral and emotional responsivity. This and future studies of
subcortical attachment systems may inform treatments for couples, parents, and related
The correlations of altruism with local brain activations and hormone function reported
here also highlight the role of “other-centered” processes, where the well-being of the other
person is the priority, sometimes even at a cost to the self. Thus, we highlight the subcortical
systems and corresponding genetic markers that may influence a complex behavior that may
benefit the pair-bond and their kin, as well as others. Together, the results provide a basis for
further research on the neural and genetic factors that mediate the complex attachment
behaviors and pro-social behaviors, which ultimately serve survival and thriving of the species.
25
Acknowledgements
This research was supported by a grant from the National Science Foundation (No. 0958171).
We thank Nancy Collins, PhD and Scott Grafton, PhD, professors in the Department of
Psychological and Brain Sciences at UCSB for providing support which made this research
possible. We also thank our research assistants Lauren Baker, Rafael Cruz, Janet Ferrer,
Cynthia Gonzales, Alexis Goswitz, Robert Marhenke, Flannery Rogers, Stephanie O’Keefe,
Jonathan Vogel, and Sheerin Zarinafsar for their assistance with this research.
26
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36
Author Note
Data from these participants’ fMRI scans have been presented elsewhere (e.g. Acevedo et al.,
2014), though no analyses in the present research are redundant with any published findings.
37
Tables
Table 1
Regions of Interest from Human and Animal Studies of Pair-bonding and Empathy
Brain Region x y z Reference(s)
Ventral pallidum* ** ** ** *1
Nucleus accumbens* ** ** ** 1
Ventral tegmentum 0-9 -12 -11/-24 2,3
Caudate ** ** ** 2, 3, 4
Putamen ** ** ** 2, 3, 4
Globus pallidus ** ** ** 2, 4
Periaqueductal gray 0 -31 -13 2, 4, 5
Hypothalamus* 0 0 -10 2, 6
Amygdala ±18 -3 -20 2,3,4,7,8
Hippocampus ± 30 -10 -18 2, 3
Parahippocampal gyrus ± 17 -11 -19 2, 4
Lateral septum/fornix area 0 -31 -13 1,2, 3, 4
Thalamus, dorsomedial n. ±5 -21 11 2, 4
Note. All regions are MNI coordinates. *Human brain regions were identified using Mai,
Paxinos and Voss, 2008. ** Extrapolated from a meta-analysis or composed of extensive
regions. References: 1. Groppe et al., 2013. 2. Acevedo et al., 2011. 3. Aron et al., 2005.
4. Bartels & Zeki, 2004. 5. Brunnlieb et al., 2016. 6. Eisenberger and Lieberman, 2004.
7. Satpute et al., 2015. 8. Ruby and Decety, 2001.
38
Table 2
Regional Brain Activations in Early-Stage Marital Pair-Bonds for the Romance Condition (Partner vs. Familiar
Face), at T1(Around the Wedding) and Replicated at T2 (One-year after the Wedding)
Time 1 Time 2
Brain Region Side x y z T p T p
Region of Interest (ROI) Activations
Note. MNI coordinates (x,y,z) are at the maximum value for the cluster, which may be elongated in any direction.
For ROIs, p values are for small volume correction (FDR).
39
Table 3
Regional Brain Activations Correlated with OXTR rs53576 (G Alleles) and Altruism scores
in Response to Viewing Happy or Sad (vs. Neutral) Partner Face Images
x y z p x y z p
Partner Happy vs. Neutral:
Positive Correlations
Ventral pallidum (VP) *,+,x -9 6 -8 0.01
Accumbens/VP -3 6 -8 0.01
Accumbens, anterior -9 15 -10 0.01
Substantia nigra -9 -7 -12 0.01
Septum/fornix area 3 0 6 0.01
Amygdala (basolateral)/
-18 0 -21 0.01 21 0 -24 0.01
Entorhinal cortex *,+,x
Periaqueductal gray + -3 -27 -10 0.03
Partner Happy vs. Stranger
Happy: Positive Correlations
Substantia nigra2 -7 -10 -14 0.05
Septum/fornix area+1,2 3 0 6 0.03
Amygdala (basolateral)/
-18 0 -24 0.03 18 0 -24 0.03
Entorhinal cortex *,+,x, 2
Periaqueductal gray +,2 -3 -27 -9 0.02 3 -27 -9 0.03
Partner Sad vs. Neutral:
Positive Correlations
VP *, x -10 7 -9 0.04
+, x
Amygdala, basolateral -19 -3 -21 0.01
x
Amygdala, central -18 -9 -15 .01
Amygdala/entorhinal cortex * -15 0 -21 0.05 15 0 -24 0.01
Entorhinal/parahippocampal
-12 -3 -22 0.01
cortex x
Partner Sad vs. Neutral:
Negative Correlations
Ventral tegmental area
0 -21 -21 0.003
(VTA)/Raphe, median*
MNI coordinates (x,y,z) are at the maximum value for the cluster, which may be elongated in any
direction. For ROIs, p values are for FDR small volume correction at p < .05.
Legend: * overlapping with OXTR rs53576, Sad; + overlapping with AVPR1a rs3, Happy; x
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overlapping with AVPR1a rs3, Sad. For the Partner versus Stranger contrasts: 1 shown at T1, 2 shown
at T2.
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Table 4
Regional Brain Activations Correlated with AVPR1aRS3 (long alleles) and Altruism Scores in
Response to Viewing Happy or Sad (vs. Neutral) Partner Face Images.
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MNI coordinates (x,y,z) are at the maximum value for the cluster, which may be elongated in
any direction. For ROIs, p values are for FDR small volume correction at p < .05. For Whole
Brain Analyses, p < .001 (unc). Legend: * overlapping with AVPR1a rs3, Sad; + overlapping
with OXTR rs53576, Happy; x overlapping with OXTR rs53576, Sad.
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Figure Captions
Figure 1. Partner Love vs. HFN contrast: VP activation (arrow) in newly-married individuals
viewing face images of a partner (vs. familiar acquaintance) replicated around the time of the
wedding (T1) and one-year after (T2). Red, T1; Green, T2; Yellow, overlapping activation at
T1 and T2. The VP voxel clusters are ROIs, predicted regions of change, at p<.05, corrected.
Figure 2. Colored voxels show neural localization for OXTR rs53576 G-alleles and altruism
score interactions in response to affective face images of the Partner (A-G) or a Stranger (H).
(A) Partner Happy vs. Neutral contrast: The location of the VP and NAcc responses (left arrow)
and septum responses (right arrow) to Happy face images, shown on a template anatomical
image.
(B) Partner Love vs. HFN contrast: Raw data echo planar image of a subject showing the
VP/accumbens cluster as seen in Figure 1a. Brain iron (black) is a marker for the GP and VP in
voles and humans.
(C) Partner Sad vs. Neutral contrast: The location of the VP cluster for Sad faces (arrow)
overlaps with the black iron marker.
(D) Partner Happy vs. Neutral and Partner Sad vs. Neutral contrasts: An enlargement of the VP
activation showing unique effects for Happy (yellow) and Sad (blue), and their overlap
(magenta). Happy included the NAcc (right arrow, yellow). Crosshairs mark the VP.
(E) Partner Happy vs. Neutral contrast: The basolateral amygdala/entorhinal cortex regions
where correlations were localized (left and right arrows).
(F) Partner Happy vs. Neutral contrast: PAG (arrow)
(G) Partner Sad vs. Neutral contrast: VTA (arrow) shows negative correlation.
(H) Stranger Happy vs. Neutral and Stranger Sad vs. Neutral contrasts: No VP activation in
response to Stranger emotion face images (arrow).
(I) Partner Happy vs. Neutral and Partner Sad vs. Neutral contrasts: VP effects in each
participant correlated with their number of OXTR rs53576 G-alleles and altruism (Agape) scores
for Happy (yellow) and Sad (blue) partner events.
Figure 3. Colored voxels show neural localization for AVPR1a rs3 long alleles and altruism
score interactions in response to affective face images of the Partner (A-G) or a Stranger (H)
(A) Partner Happy vs. Neutral contrast: The location of the GP response (arrow, yellow) shown
on an anatomical template image.
(B) Partner Happy vs. Neutral contrast: Raw data echo planar image of a subject showing the
GP cluster. This cluster is in a low iron concentration area (compared to the VP for Sad, shown
in 2c). Brain iron (black) is a marker for the GP and VP in voles and humans.
(C) Partner Sad vs. Neutral contrast: The location of the VP cluster (arrow) overlaps with the
iron marker for the VP.
(D) Partner Sad vs. Neutral contrast: An enlargement of the VP brain region showing positive
response to a partner’s sad events.
(E) Partner Happy vs. Neutral and Partner Sad vs. Neutral contrasts: The basolateral
amygdala/entorhinal cortex regions show localized effects for happy and sad partner events (left
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and right arrows).
(F) Partner Happy vs. Neutral contrast: PAG (top arrow) and SN region (bottom arrow) show
positive response.
(G) Partner Sad vs. Neutral contrast: Raphé, median (arrow) shows negative correlation.
(H) Stranger Happy vs. Neutral and Stranger Sad vs. Neutral contrasts: No VP activation in
response to Stranger happy or sad face images (arrow).
(I) Partner Happy vs. Neutral and Partner Sad vs. Neutral contrasts: VP/GP effects of each
participant correlated with their AVPR1a rs3 allele length and altruism (Agape) scores for
Happy (yellow) and Sad (blue) conditions.
Figure 4. Colored voxels show the location of neural and altruism score correlations
overlapping for both OXTR rs53576 and AVPR1a rs3.
(A) Partner Happy vs. Neutral contrasts: Positive correlations to Happy Partner face images are
shown in the basolateral amygdala region and entorhinal cortex (arrows).
Red = OXTR rs53576; Orange = overlap of OXTR rs53576 and AVPR1a rs3.
(B) Partner Sad vs. Neutral contrasts: Positive correlation responses to Sad Partner face images
are shown in the left posterior central amygdala nucleus region (arrow).
Green = AVPR1a rs3; Blue= OXTR rs53576. Magenta= overlap between OXTR rs53576 and
AVPR1a rs3.
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